CORTICAL BLINDNESS IN

PREECLEMPTIC PATIENTS

DUE TO PRES OR REGIONAL

ANESTHESIA

Sule Akin Anis Aribogan Semih Giray Zulfikar Arlier

Baskent University School of Medicine

Anesthesiology and Reanimation Department

INTRODUCTIONPREECLAMPSIA

Serious pregnancy disorder with maternalfetal risks

INTRODUCTION

PREECLAMPSİA

Hypertension

OedemaProteinuria

INTRODUCTIONPOSTERİOR REVERSİBLE ENCEPHALOPATHY

SYNDROME (PRES)

Neuroclinical pathology

Cortical changes in posterior cerebrum and cerebellum I

INTRODUCTIONPOSTERİOR REVERSİBLE ENCEPHALOPATHY

SYNDROME (PRES)

Neuroclinical pathology

Cortical changes in posterior cerebrum and cerebellum

Change in autoregulatıon of

cerebral blood flow

Cerebraloedema

Ischaemia

INTRODUCTION

PRES

CORTICAL BLINDNESS

SPINAL BLOCK FOR CS

CASES Three women Common

demographics

Young ages(19 2122

yo)

High bloodpressures

(SABPgt 180 mmHg)

Firstgestations

Spinalanesthesiatechnique

CASES

PRES DIAGNOSIS

CASES

CLINIC PRESENTATION

CORTICAL

BLINDNESS

CASES

TREATMENT

Antiedema therapy (mannitol and dexamethasone)

SABP range 140-160 mmHg

Hypervolemia

Dextran

Pentoxifylline

Low molecular weight heparin

DISCUSSION

CNS COMPLICATIONS OF PREECLEMPSIA

Eclampsia (seizures)

Cerebral haemorrhage (stroke)

Cerebral oedema

Cortical blindness

Retinal oedema

Retinal blindness

Patients claim blindness1048708 Inability to seedetect visual stimuli1048708 Eyes retinae optic nerves intact1048708 Damage is at the cortical level

Cortical Blindness

PRES(Posterior Reversible

Encephalopathy Syndrome)J Ryan Altman MD

AM Report15 July 2008

PRES

A clinical radiologic syndrome of heterogenic etiologies

Many Names Posterior Reversible Encephalopathy Syndrome (PRES)

Reversible Posterior Cerebral Edema Syndrome

Posterior Leukoencephalopathy Syndrome

Hyperperfusion Encephalopathy

Brain Capillary Leak Syndrome

PRES

Epidemiology All age groups susceptible (ages 2-90)

More common in women even when eclampsia excluded

Risk Factors

Hypertensive disorders

Renal disease

Immunosuppressive therapies

PRES

Pathogenesismdashunclear Autoregulatory Failure

Normal autoregulation maintains constant cerebral blood flow over range of systemic BP by arteriolar constriction and dilatation

As upper limits of cerebral autoregulation exceeded arterioles dilate and cerebral blood flow increases Results in brain hyperperfusion and may lead to breakdown of BBB

Chronic HTN Vascular changes ldquoresetrdquo range of autoregulation As a result pts with PRES in setting of longstanding HTN

may have markedly elevated BP while less severe elevations even nl BP are associated with PRES in other settings

PRES

Pathogenesismdashunclear Endothelial dysfunction

Cytotoxic therapies may have direct toxicity on vascular endothelium leading to

capillary leakage and BBB with axonal swelling triggering vasogenic edema

may occur in normotensive individuals with nontoxic levels of these drugs

Preeclampsia PRES best dx by elevated markers

Elevated endothelial cell markers fibronectin tPA thrombomodulin endothelin-1 von Willebrand factor Markers also elevated in PRES associated with chronic renal

failure lupus nephritis HUS

Other possible causes uremia sepsis hypomagnesemia fluid overload

PRES

Anatomy Combination of acute HTN and endothelial damage

results in hydrostatic edema (type of vasogenic edema characterized by forced leakage of serum through capillary walls and into the brain interstitium)

The cortex structurally more tightly packed than the white matter resists accumulation of edema hence predilection of abnormalities in white matter

Primary involvement of posterior brain regions not well understood (One thought is regional heterogeneity of sympathetic nerve innervation of intracranial arterioles which protects the brain from marked increases in BP have greater concentration around pial and intracerebral vessels in anterior cirulation)

PRES

Associated Conditions Comorbidities that exacerbate neurologic deterioration ischemic bowel disease sepsis hyponatremia fever proteinuria

Hypertensive Encephalopathy PRES likely caused by vasogenic edema from

breakthrough of autoregulation Risk for HE rapidly developing fluctuating or

intermittent hypertension May be seen in pts with chronic HTN renal failure or

preeclampsia-eclampsia Percent elevation of BP above baseline as well as

severity of HTN are associated with development of PRES Therefore it may occur in normotensive pts

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

INTRODUCTION

PREECLAMPSİA

Hypertension

OedemaProteinuria

INTRODUCTIONPOSTERİOR REVERSİBLE ENCEPHALOPATHY

SYNDROME (PRES)

Neuroclinical pathology

Cortical changes in posterior cerebrum and cerebellum I

INTRODUCTIONPOSTERİOR REVERSİBLE ENCEPHALOPATHY

SYNDROME (PRES)

Neuroclinical pathology

Cortical changes in posterior cerebrum and cerebellum

Change in autoregulatıon of

cerebral blood flow

Cerebraloedema

Ischaemia

INTRODUCTION

PRES

CORTICAL BLINDNESS

SPINAL BLOCK FOR CS

CASES Three women Common

demographics

Young ages(19 2122

yo)

High bloodpressures

(SABPgt 180 mmHg)

Firstgestations

Spinalanesthesiatechnique

CASES

PRES DIAGNOSIS

CASES

CLINIC PRESENTATION

CORTICAL

BLINDNESS

CASES

TREATMENT

Antiedema therapy (mannitol and dexamethasone)

SABP range 140-160 mmHg

Hypervolemia

Dextran

Pentoxifylline

Low molecular weight heparin

DISCUSSION

CNS COMPLICATIONS OF PREECLEMPSIA

Eclampsia (seizures)

Cerebral haemorrhage (stroke)

Cerebral oedema

Cortical blindness

Retinal oedema

Retinal blindness

Patients claim blindness1048708 Inability to seedetect visual stimuli1048708 Eyes retinae optic nerves intact1048708 Damage is at the cortical level

Cortical Blindness

PRES(Posterior Reversible

Encephalopathy Syndrome)J Ryan Altman MD

AM Report15 July 2008

PRES

A clinical radiologic syndrome of heterogenic etiologies

Many Names Posterior Reversible Encephalopathy Syndrome (PRES)

Reversible Posterior Cerebral Edema Syndrome

Posterior Leukoencephalopathy Syndrome

Hyperperfusion Encephalopathy

Brain Capillary Leak Syndrome

PRES

Epidemiology All age groups susceptible (ages 2-90)

More common in women even when eclampsia excluded

Risk Factors

Hypertensive disorders

Renal disease

Immunosuppressive therapies

PRES

Pathogenesismdashunclear Autoregulatory Failure

Normal autoregulation maintains constant cerebral blood flow over range of systemic BP by arteriolar constriction and dilatation

As upper limits of cerebral autoregulation exceeded arterioles dilate and cerebral blood flow increases Results in brain hyperperfusion and may lead to breakdown of BBB

Chronic HTN Vascular changes ldquoresetrdquo range of autoregulation As a result pts with PRES in setting of longstanding HTN

may have markedly elevated BP while less severe elevations even nl BP are associated with PRES in other settings

PRES

Pathogenesismdashunclear Endothelial dysfunction

Cytotoxic therapies may have direct toxicity on vascular endothelium leading to

capillary leakage and BBB with axonal swelling triggering vasogenic edema

may occur in normotensive individuals with nontoxic levels of these drugs

Preeclampsia PRES best dx by elevated markers

Elevated endothelial cell markers fibronectin tPA thrombomodulin endothelin-1 von Willebrand factor Markers also elevated in PRES associated with chronic renal

failure lupus nephritis HUS

Other possible causes uremia sepsis hypomagnesemia fluid overload

PRES

Anatomy Combination of acute HTN and endothelial damage

results in hydrostatic edema (type of vasogenic edema characterized by forced leakage of serum through capillary walls and into the brain interstitium)

The cortex structurally more tightly packed than the white matter resists accumulation of edema hence predilection of abnormalities in white matter

Primary involvement of posterior brain regions not well understood (One thought is regional heterogeneity of sympathetic nerve innervation of intracranial arterioles which protects the brain from marked increases in BP have greater concentration around pial and intracerebral vessels in anterior cirulation)

PRES

Associated Conditions Comorbidities that exacerbate neurologic deterioration ischemic bowel disease sepsis hyponatremia fever proteinuria

Hypertensive Encephalopathy PRES likely caused by vasogenic edema from

breakthrough of autoregulation Risk for HE rapidly developing fluctuating or

intermittent hypertension May be seen in pts with chronic HTN renal failure or

preeclampsia-eclampsia Percent elevation of BP above baseline as well as

severity of HTN are associated with development of PRES Therefore it may occur in normotensive pts

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

INTRODUCTIONPOSTERİOR REVERSİBLE ENCEPHALOPATHY

SYNDROME (PRES)

Neuroclinical pathology

Cortical changes in posterior cerebrum and cerebellum I

INTRODUCTIONPOSTERİOR REVERSİBLE ENCEPHALOPATHY

SYNDROME (PRES)

Neuroclinical pathology

Cortical changes in posterior cerebrum and cerebellum

Change in autoregulatıon of

cerebral blood flow

Cerebraloedema

Ischaemia

INTRODUCTION

PRES

CORTICAL BLINDNESS

SPINAL BLOCK FOR CS

CASES Three women Common

demographics

Young ages(19 2122

yo)

High bloodpressures

(SABPgt 180 mmHg)

Firstgestations

Spinalanesthesiatechnique

CASES

PRES DIAGNOSIS

CASES

CLINIC PRESENTATION

CORTICAL

BLINDNESS

CASES

TREATMENT

Antiedema therapy (mannitol and dexamethasone)

SABP range 140-160 mmHg

Hypervolemia

Dextran

Pentoxifylline

Low molecular weight heparin

DISCUSSION

CNS COMPLICATIONS OF PREECLEMPSIA

Eclampsia (seizures)

Cerebral haemorrhage (stroke)

Cerebral oedema

Cortical blindness

Retinal oedema

Retinal blindness

Patients claim blindness1048708 Inability to seedetect visual stimuli1048708 Eyes retinae optic nerves intact1048708 Damage is at the cortical level

Cortical Blindness

PRES(Posterior Reversible

Encephalopathy Syndrome)J Ryan Altman MD

AM Report15 July 2008

PRES

A clinical radiologic syndrome of heterogenic etiologies

Many Names Posterior Reversible Encephalopathy Syndrome (PRES)

Reversible Posterior Cerebral Edema Syndrome

Posterior Leukoencephalopathy Syndrome

Hyperperfusion Encephalopathy

Brain Capillary Leak Syndrome

PRES

Epidemiology All age groups susceptible (ages 2-90)

More common in women even when eclampsia excluded

Risk Factors

Hypertensive disorders

Renal disease

Immunosuppressive therapies

PRES

Pathogenesismdashunclear Autoregulatory Failure

Normal autoregulation maintains constant cerebral blood flow over range of systemic BP by arteriolar constriction and dilatation

As upper limits of cerebral autoregulation exceeded arterioles dilate and cerebral blood flow increases Results in brain hyperperfusion and may lead to breakdown of BBB

Chronic HTN Vascular changes ldquoresetrdquo range of autoregulation As a result pts with PRES in setting of longstanding HTN

may have markedly elevated BP while less severe elevations even nl BP are associated with PRES in other settings

PRES

Pathogenesismdashunclear Endothelial dysfunction

Cytotoxic therapies may have direct toxicity on vascular endothelium leading to

capillary leakage and BBB with axonal swelling triggering vasogenic edema

may occur in normotensive individuals with nontoxic levels of these drugs

Preeclampsia PRES best dx by elevated markers

Elevated endothelial cell markers fibronectin tPA thrombomodulin endothelin-1 von Willebrand factor Markers also elevated in PRES associated with chronic renal

failure lupus nephritis HUS

Other possible causes uremia sepsis hypomagnesemia fluid overload

PRES

Anatomy Combination of acute HTN and endothelial damage

results in hydrostatic edema (type of vasogenic edema characterized by forced leakage of serum through capillary walls and into the brain interstitium)

The cortex structurally more tightly packed than the white matter resists accumulation of edema hence predilection of abnormalities in white matter

Primary involvement of posterior brain regions not well understood (One thought is regional heterogeneity of sympathetic nerve innervation of intracranial arterioles which protects the brain from marked increases in BP have greater concentration around pial and intracerebral vessels in anterior cirulation)

PRES

Associated Conditions Comorbidities that exacerbate neurologic deterioration ischemic bowel disease sepsis hyponatremia fever proteinuria

Hypertensive Encephalopathy PRES likely caused by vasogenic edema from

breakthrough of autoregulation Risk for HE rapidly developing fluctuating or

intermittent hypertension May be seen in pts with chronic HTN renal failure or

preeclampsia-eclampsia Percent elevation of BP above baseline as well as

severity of HTN are associated with development of PRES Therefore it may occur in normotensive pts

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

INTRODUCTIONPOSTERİOR REVERSİBLE ENCEPHALOPATHY

SYNDROME (PRES)

Neuroclinical pathology

Cortical changes in posterior cerebrum and cerebellum

Change in autoregulatıon of

cerebral blood flow

Cerebraloedema

Ischaemia

INTRODUCTION

PRES

CORTICAL BLINDNESS

SPINAL BLOCK FOR CS

CASES Three women Common

demographics

Young ages(19 2122

yo)

High bloodpressures

(SABPgt 180 mmHg)

Firstgestations

Spinalanesthesiatechnique

CASES

PRES DIAGNOSIS

CASES

CLINIC PRESENTATION

CORTICAL

BLINDNESS

CASES

TREATMENT

Antiedema therapy (mannitol and dexamethasone)

SABP range 140-160 mmHg

Hypervolemia

Dextran

Pentoxifylline

Low molecular weight heparin

DISCUSSION

CNS COMPLICATIONS OF PREECLEMPSIA

Eclampsia (seizures)

Cerebral haemorrhage (stroke)

Cerebral oedema

Cortical blindness

Retinal oedema

Retinal blindness

Patients claim blindness1048708 Inability to seedetect visual stimuli1048708 Eyes retinae optic nerves intact1048708 Damage is at the cortical level

Cortical Blindness

PRES(Posterior Reversible

Encephalopathy Syndrome)J Ryan Altman MD

AM Report15 July 2008

PRES

A clinical radiologic syndrome of heterogenic etiologies

Many Names Posterior Reversible Encephalopathy Syndrome (PRES)

Reversible Posterior Cerebral Edema Syndrome

Posterior Leukoencephalopathy Syndrome

Hyperperfusion Encephalopathy

Brain Capillary Leak Syndrome

PRES

Epidemiology All age groups susceptible (ages 2-90)

More common in women even when eclampsia excluded

Risk Factors

Hypertensive disorders

Renal disease

Immunosuppressive therapies

PRES

Pathogenesismdashunclear Autoregulatory Failure

Normal autoregulation maintains constant cerebral blood flow over range of systemic BP by arteriolar constriction and dilatation

As upper limits of cerebral autoregulation exceeded arterioles dilate and cerebral blood flow increases Results in brain hyperperfusion and may lead to breakdown of BBB

Chronic HTN Vascular changes ldquoresetrdquo range of autoregulation As a result pts with PRES in setting of longstanding HTN

may have markedly elevated BP while less severe elevations even nl BP are associated with PRES in other settings

PRES

Pathogenesismdashunclear Endothelial dysfunction

Cytotoxic therapies may have direct toxicity on vascular endothelium leading to

capillary leakage and BBB with axonal swelling triggering vasogenic edema

may occur in normotensive individuals with nontoxic levels of these drugs

Preeclampsia PRES best dx by elevated markers

Elevated endothelial cell markers fibronectin tPA thrombomodulin endothelin-1 von Willebrand factor Markers also elevated in PRES associated with chronic renal

failure lupus nephritis HUS

Other possible causes uremia sepsis hypomagnesemia fluid overload

PRES

Anatomy Combination of acute HTN and endothelial damage

results in hydrostatic edema (type of vasogenic edema characterized by forced leakage of serum through capillary walls and into the brain interstitium)

The cortex structurally more tightly packed than the white matter resists accumulation of edema hence predilection of abnormalities in white matter

Primary involvement of posterior brain regions not well understood (One thought is regional heterogeneity of sympathetic nerve innervation of intracranial arterioles which protects the brain from marked increases in BP have greater concentration around pial and intracerebral vessels in anterior cirulation)

PRES

Associated Conditions Comorbidities that exacerbate neurologic deterioration ischemic bowel disease sepsis hyponatremia fever proteinuria

Hypertensive Encephalopathy PRES likely caused by vasogenic edema from

breakthrough of autoregulation Risk for HE rapidly developing fluctuating or

intermittent hypertension May be seen in pts with chronic HTN renal failure or

preeclampsia-eclampsia Percent elevation of BP above baseline as well as

severity of HTN are associated with development of PRES Therefore it may occur in normotensive pts

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

INTRODUCTION

PRES

CORTICAL BLINDNESS

SPINAL BLOCK FOR CS

CASES Three women Common

demographics

Young ages(19 2122

yo)

High bloodpressures

(SABPgt 180 mmHg)

Firstgestations

Spinalanesthesiatechnique

CASES

PRES DIAGNOSIS

CASES

CLINIC PRESENTATION

CORTICAL

BLINDNESS

CASES

TREATMENT

Antiedema therapy (mannitol and dexamethasone)

SABP range 140-160 mmHg

Hypervolemia

Dextran

Pentoxifylline

Low molecular weight heparin

DISCUSSION

CNS COMPLICATIONS OF PREECLEMPSIA

Eclampsia (seizures)

Cerebral haemorrhage (stroke)

Cerebral oedema

Cortical blindness

Retinal oedema

Retinal blindness

Patients claim blindness1048708 Inability to seedetect visual stimuli1048708 Eyes retinae optic nerves intact1048708 Damage is at the cortical level

Cortical Blindness

PRES(Posterior Reversible

Encephalopathy Syndrome)J Ryan Altman MD

AM Report15 July 2008

PRES

A clinical radiologic syndrome of heterogenic etiologies

Many Names Posterior Reversible Encephalopathy Syndrome (PRES)

Reversible Posterior Cerebral Edema Syndrome

Posterior Leukoencephalopathy Syndrome

Hyperperfusion Encephalopathy

Brain Capillary Leak Syndrome

PRES

Epidemiology All age groups susceptible (ages 2-90)

More common in women even when eclampsia excluded

Risk Factors

Hypertensive disorders

Renal disease

Immunosuppressive therapies

PRES

Pathogenesismdashunclear Autoregulatory Failure

Normal autoregulation maintains constant cerebral blood flow over range of systemic BP by arteriolar constriction and dilatation

As upper limits of cerebral autoregulation exceeded arterioles dilate and cerebral blood flow increases Results in brain hyperperfusion and may lead to breakdown of BBB

Chronic HTN Vascular changes ldquoresetrdquo range of autoregulation As a result pts with PRES in setting of longstanding HTN

may have markedly elevated BP while less severe elevations even nl BP are associated with PRES in other settings

PRES

Pathogenesismdashunclear Endothelial dysfunction

Cytotoxic therapies may have direct toxicity on vascular endothelium leading to

capillary leakage and BBB with axonal swelling triggering vasogenic edema

may occur in normotensive individuals with nontoxic levels of these drugs

Preeclampsia PRES best dx by elevated markers

Elevated endothelial cell markers fibronectin tPA thrombomodulin endothelin-1 von Willebrand factor Markers also elevated in PRES associated with chronic renal

failure lupus nephritis HUS

Other possible causes uremia sepsis hypomagnesemia fluid overload

PRES

Anatomy Combination of acute HTN and endothelial damage

results in hydrostatic edema (type of vasogenic edema characterized by forced leakage of serum through capillary walls and into the brain interstitium)

The cortex structurally more tightly packed than the white matter resists accumulation of edema hence predilection of abnormalities in white matter

Primary involvement of posterior brain regions not well understood (One thought is regional heterogeneity of sympathetic nerve innervation of intracranial arterioles which protects the brain from marked increases in BP have greater concentration around pial and intracerebral vessels in anterior cirulation)

PRES

Associated Conditions Comorbidities that exacerbate neurologic deterioration ischemic bowel disease sepsis hyponatremia fever proteinuria

Hypertensive Encephalopathy PRES likely caused by vasogenic edema from

breakthrough of autoregulation Risk for HE rapidly developing fluctuating or

intermittent hypertension May be seen in pts with chronic HTN renal failure or

preeclampsia-eclampsia Percent elevation of BP above baseline as well as

severity of HTN are associated with development of PRES Therefore it may occur in normotensive pts

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

CASES Three women Common

demographics

Young ages(19 2122

yo)

High bloodpressures

(SABPgt 180 mmHg)

Firstgestations

Spinalanesthesiatechnique

CASES

PRES DIAGNOSIS

CASES

CLINIC PRESENTATION

CORTICAL

BLINDNESS

CASES

TREATMENT

Antiedema therapy (mannitol and dexamethasone)

SABP range 140-160 mmHg

Hypervolemia

Dextran

Pentoxifylline

Low molecular weight heparin

DISCUSSION

CNS COMPLICATIONS OF PREECLEMPSIA

Eclampsia (seizures)

Cerebral haemorrhage (stroke)

Cerebral oedema

Cortical blindness

Retinal oedema

Retinal blindness

Patients claim blindness1048708 Inability to seedetect visual stimuli1048708 Eyes retinae optic nerves intact1048708 Damage is at the cortical level

Cortical Blindness

PRES(Posterior Reversible

Encephalopathy Syndrome)J Ryan Altman MD

AM Report15 July 2008

PRES

A clinical radiologic syndrome of heterogenic etiologies

Many Names Posterior Reversible Encephalopathy Syndrome (PRES)

Reversible Posterior Cerebral Edema Syndrome

Posterior Leukoencephalopathy Syndrome

Hyperperfusion Encephalopathy

Brain Capillary Leak Syndrome

PRES

Epidemiology All age groups susceptible (ages 2-90)

More common in women even when eclampsia excluded

Risk Factors

Hypertensive disorders

Renal disease

Immunosuppressive therapies

PRES

Pathogenesismdashunclear Autoregulatory Failure

Normal autoregulation maintains constant cerebral blood flow over range of systemic BP by arteriolar constriction and dilatation

As upper limits of cerebral autoregulation exceeded arterioles dilate and cerebral blood flow increases Results in brain hyperperfusion and may lead to breakdown of BBB

Chronic HTN Vascular changes ldquoresetrdquo range of autoregulation As a result pts with PRES in setting of longstanding HTN

may have markedly elevated BP while less severe elevations even nl BP are associated with PRES in other settings

PRES

Pathogenesismdashunclear Endothelial dysfunction

Cytotoxic therapies may have direct toxicity on vascular endothelium leading to

capillary leakage and BBB with axonal swelling triggering vasogenic edema

may occur in normotensive individuals with nontoxic levels of these drugs

Preeclampsia PRES best dx by elevated markers

Elevated endothelial cell markers fibronectin tPA thrombomodulin endothelin-1 von Willebrand factor Markers also elevated in PRES associated with chronic renal

failure lupus nephritis HUS

Other possible causes uremia sepsis hypomagnesemia fluid overload

PRES

Anatomy Combination of acute HTN and endothelial damage

results in hydrostatic edema (type of vasogenic edema characterized by forced leakage of serum through capillary walls and into the brain interstitium)

The cortex structurally more tightly packed than the white matter resists accumulation of edema hence predilection of abnormalities in white matter

Primary involvement of posterior brain regions not well understood (One thought is regional heterogeneity of sympathetic nerve innervation of intracranial arterioles which protects the brain from marked increases in BP have greater concentration around pial and intracerebral vessels in anterior cirulation)

PRES

Associated Conditions Comorbidities that exacerbate neurologic deterioration ischemic bowel disease sepsis hyponatremia fever proteinuria

Hypertensive Encephalopathy PRES likely caused by vasogenic edema from

breakthrough of autoregulation Risk for HE rapidly developing fluctuating or

intermittent hypertension May be seen in pts with chronic HTN renal failure or

preeclampsia-eclampsia Percent elevation of BP above baseline as well as

severity of HTN are associated with development of PRES Therefore it may occur in normotensive pts

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

CASES

PRES DIAGNOSIS

CASES

CLINIC PRESENTATION

CORTICAL

BLINDNESS

CASES

TREATMENT

Antiedema therapy (mannitol and dexamethasone)

SABP range 140-160 mmHg

Hypervolemia

Dextran

Pentoxifylline

Low molecular weight heparin

DISCUSSION

CNS COMPLICATIONS OF PREECLEMPSIA

Eclampsia (seizures)

Cerebral haemorrhage (stroke)

Cerebral oedema

Cortical blindness

Retinal oedema

Retinal blindness

Patients claim blindness1048708 Inability to seedetect visual stimuli1048708 Eyes retinae optic nerves intact1048708 Damage is at the cortical level

Cortical Blindness

PRES(Posterior Reversible

Encephalopathy Syndrome)J Ryan Altman MD

AM Report15 July 2008

PRES

A clinical radiologic syndrome of heterogenic etiologies

Many Names Posterior Reversible Encephalopathy Syndrome (PRES)

Reversible Posterior Cerebral Edema Syndrome

Posterior Leukoencephalopathy Syndrome

Hyperperfusion Encephalopathy

Brain Capillary Leak Syndrome

PRES

Epidemiology All age groups susceptible (ages 2-90)

More common in women even when eclampsia excluded

Risk Factors

Hypertensive disorders

Renal disease

Immunosuppressive therapies

PRES

Pathogenesismdashunclear Autoregulatory Failure

Normal autoregulation maintains constant cerebral blood flow over range of systemic BP by arteriolar constriction and dilatation

As upper limits of cerebral autoregulation exceeded arterioles dilate and cerebral blood flow increases Results in brain hyperperfusion and may lead to breakdown of BBB

Chronic HTN Vascular changes ldquoresetrdquo range of autoregulation As a result pts with PRES in setting of longstanding HTN

may have markedly elevated BP while less severe elevations even nl BP are associated with PRES in other settings

PRES

Pathogenesismdashunclear Endothelial dysfunction

Cytotoxic therapies may have direct toxicity on vascular endothelium leading to

capillary leakage and BBB with axonal swelling triggering vasogenic edema

may occur in normotensive individuals with nontoxic levels of these drugs

Preeclampsia PRES best dx by elevated markers

Elevated endothelial cell markers fibronectin tPA thrombomodulin endothelin-1 von Willebrand factor Markers also elevated in PRES associated with chronic renal

failure lupus nephritis HUS

Other possible causes uremia sepsis hypomagnesemia fluid overload

PRES

Anatomy Combination of acute HTN and endothelial damage

results in hydrostatic edema (type of vasogenic edema characterized by forced leakage of serum through capillary walls and into the brain interstitium)

The cortex structurally more tightly packed than the white matter resists accumulation of edema hence predilection of abnormalities in white matter

Primary involvement of posterior brain regions not well understood (One thought is regional heterogeneity of sympathetic nerve innervation of intracranial arterioles which protects the brain from marked increases in BP have greater concentration around pial and intracerebral vessels in anterior cirulation)

PRES

Associated Conditions Comorbidities that exacerbate neurologic deterioration ischemic bowel disease sepsis hyponatremia fever proteinuria

Hypertensive Encephalopathy PRES likely caused by vasogenic edema from

breakthrough of autoregulation Risk for HE rapidly developing fluctuating or

intermittent hypertension May be seen in pts with chronic HTN renal failure or

preeclampsia-eclampsia Percent elevation of BP above baseline as well as

severity of HTN are associated with development of PRES Therefore it may occur in normotensive pts

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

CASES

CLINIC PRESENTATION

CORTICAL

BLINDNESS

CASES

TREATMENT

Antiedema therapy (mannitol and dexamethasone)

SABP range 140-160 mmHg

Hypervolemia

Dextran

Pentoxifylline

Low molecular weight heparin

DISCUSSION

CNS COMPLICATIONS OF PREECLEMPSIA

Eclampsia (seizures)

Cerebral haemorrhage (stroke)

Cerebral oedema

Cortical blindness

Retinal oedema

Retinal blindness

Patients claim blindness1048708 Inability to seedetect visual stimuli1048708 Eyes retinae optic nerves intact1048708 Damage is at the cortical level

Cortical Blindness

PRES(Posterior Reversible

Encephalopathy Syndrome)J Ryan Altman MD

AM Report15 July 2008

PRES

A clinical radiologic syndrome of heterogenic etiologies

Many Names Posterior Reversible Encephalopathy Syndrome (PRES)

Reversible Posterior Cerebral Edema Syndrome

Posterior Leukoencephalopathy Syndrome

Hyperperfusion Encephalopathy

Brain Capillary Leak Syndrome

PRES

Epidemiology All age groups susceptible (ages 2-90)

More common in women even when eclampsia excluded

Risk Factors

Hypertensive disorders

Renal disease

Immunosuppressive therapies

PRES

Pathogenesismdashunclear Autoregulatory Failure

Normal autoregulation maintains constant cerebral blood flow over range of systemic BP by arteriolar constriction and dilatation

As upper limits of cerebral autoregulation exceeded arterioles dilate and cerebral blood flow increases Results in brain hyperperfusion and may lead to breakdown of BBB

Chronic HTN Vascular changes ldquoresetrdquo range of autoregulation As a result pts with PRES in setting of longstanding HTN

may have markedly elevated BP while less severe elevations even nl BP are associated with PRES in other settings

PRES

Pathogenesismdashunclear Endothelial dysfunction

Cytotoxic therapies may have direct toxicity on vascular endothelium leading to

capillary leakage and BBB with axonal swelling triggering vasogenic edema

may occur in normotensive individuals with nontoxic levels of these drugs

Preeclampsia PRES best dx by elevated markers

Elevated endothelial cell markers fibronectin tPA thrombomodulin endothelin-1 von Willebrand factor Markers also elevated in PRES associated with chronic renal

failure lupus nephritis HUS

Other possible causes uremia sepsis hypomagnesemia fluid overload

PRES

Anatomy Combination of acute HTN and endothelial damage

results in hydrostatic edema (type of vasogenic edema characterized by forced leakage of serum through capillary walls and into the brain interstitium)

The cortex structurally more tightly packed than the white matter resists accumulation of edema hence predilection of abnormalities in white matter

Primary involvement of posterior brain regions not well understood (One thought is regional heterogeneity of sympathetic nerve innervation of intracranial arterioles which protects the brain from marked increases in BP have greater concentration around pial and intracerebral vessels in anterior cirulation)

PRES

Associated Conditions Comorbidities that exacerbate neurologic deterioration ischemic bowel disease sepsis hyponatremia fever proteinuria

Hypertensive Encephalopathy PRES likely caused by vasogenic edema from

breakthrough of autoregulation Risk for HE rapidly developing fluctuating or

intermittent hypertension May be seen in pts with chronic HTN renal failure or

preeclampsia-eclampsia Percent elevation of BP above baseline as well as

severity of HTN are associated with development of PRES Therefore it may occur in normotensive pts

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

CASES

TREATMENT

Antiedema therapy (mannitol and dexamethasone)

SABP range 140-160 mmHg

Hypervolemia

Dextran

Pentoxifylline

Low molecular weight heparin

DISCUSSION

CNS COMPLICATIONS OF PREECLEMPSIA

Eclampsia (seizures)

Cerebral haemorrhage (stroke)

Cerebral oedema

Cortical blindness

Retinal oedema

Retinal blindness

Patients claim blindness1048708 Inability to seedetect visual stimuli1048708 Eyes retinae optic nerves intact1048708 Damage is at the cortical level

Cortical Blindness

PRES(Posterior Reversible

Encephalopathy Syndrome)J Ryan Altman MD

AM Report15 July 2008

PRES

A clinical radiologic syndrome of heterogenic etiologies

Many Names Posterior Reversible Encephalopathy Syndrome (PRES)

Reversible Posterior Cerebral Edema Syndrome

Posterior Leukoencephalopathy Syndrome

Hyperperfusion Encephalopathy

Brain Capillary Leak Syndrome

PRES

Epidemiology All age groups susceptible (ages 2-90)

More common in women even when eclampsia excluded

Risk Factors

Hypertensive disorders

Renal disease

Immunosuppressive therapies

PRES

Pathogenesismdashunclear Autoregulatory Failure

Normal autoregulation maintains constant cerebral blood flow over range of systemic BP by arteriolar constriction and dilatation

As upper limits of cerebral autoregulation exceeded arterioles dilate and cerebral blood flow increases Results in brain hyperperfusion and may lead to breakdown of BBB

Chronic HTN Vascular changes ldquoresetrdquo range of autoregulation As a result pts with PRES in setting of longstanding HTN

may have markedly elevated BP while less severe elevations even nl BP are associated with PRES in other settings

PRES

Pathogenesismdashunclear Endothelial dysfunction

Cytotoxic therapies may have direct toxicity on vascular endothelium leading to

capillary leakage and BBB with axonal swelling triggering vasogenic edema

may occur in normotensive individuals with nontoxic levels of these drugs

Preeclampsia PRES best dx by elevated markers

Elevated endothelial cell markers fibronectin tPA thrombomodulin endothelin-1 von Willebrand factor Markers also elevated in PRES associated with chronic renal

failure lupus nephritis HUS

Other possible causes uremia sepsis hypomagnesemia fluid overload

PRES

Anatomy Combination of acute HTN and endothelial damage

results in hydrostatic edema (type of vasogenic edema characterized by forced leakage of serum through capillary walls and into the brain interstitium)

The cortex structurally more tightly packed than the white matter resists accumulation of edema hence predilection of abnormalities in white matter

Primary involvement of posterior brain regions not well understood (One thought is regional heterogeneity of sympathetic nerve innervation of intracranial arterioles which protects the brain from marked increases in BP have greater concentration around pial and intracerebral vessels in anterior cirulation)

PRES

Associated Conditions Comorbidities that exacerbate neurologic deterioration ischemic bowel disease sepsis hyponatremia fever proteinuria

Hypertensive Encephalopathy PRES likely caused by vasogenic edema from

breakthrough of autoregulation Risk for HE rapidly developing fluctuating or

intermittent hypertension May be seen in pts with chronic HTN renal failure or

preeclampsia-eclampsia Percent elevation of BP above baseline as well as

severity of HTN are associated with development of PRES Therefore it may occur in normotensive pts

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

DISCUSSION

CNS COMPLICATIONS OF PREECLEMPSIA

Eclampsia (seizures)

Cerebral haemorrhage (stroke)

Cerebral oedema

Cortical blindness

Retinal oedema

Retinal blindness

Patients claim blindness1048708 Inability to seedetect visual stimuli1048708 Eyes retinae optic nerves intact1048708 Damage is at the cortical level

Cortical Blindness

PRES(Posterior Reversible

Encephalopathy Syndrome)J Ryan Altman MD

AM Report15 July 2008

PRES

A clinical radiologic syndrome of heterogenic etiologies

Many Names Posterior Reversible Encephalopathy Syndrome (PRES)

Reversible Posterior Cerebral Edema Syndrome

Posterior Leukoencephalopathy Syndrome

Hyperperfusion Encephalopathy

Brain Capillary Leak Syndrome

PRES

Epidemiology All age groups susceptible (ages 2-90)

More common in women even when eclampsia excluded

Risk Factors

Hypertensive disorders

Renal disease

Immunosuppressive therapies

PRES

Pathogenesismdashunclear Autoregulatory Failure

Normal autoregulation maintains constant cerebral blood flow over range of systemic BP by arteriolar constriction and dilatation

As upper limits of cerebral autoregulation exceeded arterioles dilate and cerebral blood flow increases Results in brain hyperperfusion and may lead to breakdown of BBB

Chronic HTN Vascular changes ldquoresetrdquo range of autoregulation As a result pts with PRES in setting of longstanding HTN

may have markedly elevated BP while less severe elevations even nl BP are associated with PRES in other settings

PRES

Pathogenesismdashunclear Endothelial dysfunction

Cytotoxic therapies may have direct toxicity on vascular endothelium leading to

capillary leakage and BBB with axonal swelling triggering vasogenic edema

may occur in normotensive individuals with nontoxic levels of these drugs

Preeclampsia PRES best dx by elevated markers

Elevated endothelial cell markers fibronectin tPA thrombomodulin endothelin-1 von Willebrand factor Markers also elevated in PRES associated with chronic renal

failure lupus nephritis HUS

Other possible causes uremia sepsis hypomagnesemia fluid overload

PRES

Anatomy Combination of acute HTN and endothelial damage

results in hydrostatic edema (type of vasogenic edema characterized by forced leakage of serum through capillary walls and into the brain interstitium)

The cortex structurally more tightly packed than the white matter resists accumulation of edema hence predilection of abnormalities in white matter

Primary involvement of posterior brain regions not well understood (One thought is regional heterogeneity of sympathetic nerve innervation of intracranial arterioles which protects the brain from marked increases in BP have greater concentration around pial and intracerebral vessels in anterior cirulation)

PRES

Associated Conditions Comorbidities that exacerbate neurologic deterioration ischemic bowel disease sepsis hyponatremia fever proteinuria

Hypertensive Encephalopathy PRES likely caused by vasogenic edema from

breakthrough of autoregulation Risk for HE rapidly developing fluctuating or

intermittent hypertension May be seen in pts with chronic HTN renal failure or

preeclampsia-eclampsia Percent elevation of BP above baseline as well as

severity of HTN are associated with development of PRES Therefore it may occur in normotensive pts

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

Patients claim blindness1048708 Inability to seedetect visual stimuli1048708 Eyes retinae optic nerves intact1048708 Damage is at the cortical level

Cortical Blindness

PRES(Posterior Reversible

Encephalopathy Syndrome)J Ryan Altman MD

AM Report15 July 2008

PRES

A clinical radiologic syndrome of heterogenic etiologies

Many Names Posterior Reversible Encephalopathy Syndrome (PRES)

Reversible Posterior Cerebral Edema Syndrome

Posterior Leukoencephalopathy Syndrome

Hyperperfusion Encephalopathy

Brain Capillary Leak Syndrome

PRES

Epidemiology All age groups susceptible (ages 2-90)

More common in women even when eclampsia excluded

Risk Factors

Hypertensive disorders

Renal disease

Immunosuppressive therapies

PRES

Pathogenesismdashunclear Autoregulatory Failure

Normal autoregulation maintains constant cerebral blood flow over range of systemic BP by arteriolar constriction and dilatation

As upper limits of cerebral autoregulation exceeded arterioles dilate and cerebral blood flow increases Results in brain hyperperfusion and may lead to breakdown of BBB

Chronic HTN Vascular changes ldquoresetrdquo range of autoregulation As a result pts with PRES in setting of longstanding HTN

may have markedly elevated BP while less severe elevations even nl BP are associated with PRES in other settings

PRES

Pathogenesismdashunclear Endothelial dysfunction

Cytotoxic therapies may have direct toxicity on vascular endothelium leading to

capillary leakage and BBB with axonal swelling triggering vasogenic edema

may occur in normotensive individuals with nontoxic levels of these drugs

Preeclampsia PRES best dx by elevated markers

Elevated endothelial cell markers fibronectin tPA thrombomodulin endothelin-1 von Willebrand factor Markers also elevated in PRES associated with chronic renal

failure lupus nephritis HUS

Other possible causes uremia sepsis hypomagnesemia fluid overload

PRES

Anatomy Combination of acute HTN and endothelial damage

results in hydrostatic edema (type of vasogenic edema characterized by forced leakage of serum through capillary walls and into the brain interstitium)

The cortex structurally more tightly packed than the white matter resists accumulation of edema hence predilection of abnormalities in white matter

Primary involvement of posterior brain regions not well understood (One thought is regional heterogeneity of sympathetic nerve innervation of intracranial arterioles which protects the brain from marked increases in BP have greater concentration around pial and intracerebral vessels in anterior cirulation)

PRES

Associated Conditions Comorbidities that exacerbate neurologic deterioration ischemic bowel disease sepsis hyponatremia fever proteinuria

Hypertensive Encephalopathy PRES likely caused by vasogenic edema from

breakthrough of autoregulation Risk for HE rapidly developing fluctuating or

intermittent hypertension May be seen in pts with chronic HTN renal failure or

preeclampsia-eclampsia Percent elevation of BP above baseline as well as

severity of HTN are associated with development of PRES Therefore it may occur in normotensive pts

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

PRES(Posterior Reversible

Encephalopathy Syndrome)J Ryan Altman MD

AM Report15 July 2008

PRES

A clinical radiologic syndrome of heterogenic etiologies

Many Names Posterior Reversible Encephalopathy Syndrome (PRES)

Reversible Posterior Cerebral Edema Syndrome

Posterior Leukoencephalopathy Syndrome

Hyperperfusion Encephalopathy

Brain Capillary Leak Syndrome

PRES

Epidemiology All age groups susceptible (ages 2-90)

More common in women even when eclampsia excluded

Risk Factors

Hypertensive disorders

Renal disease

Immunosuppressive therapies

PRES

Pathogenesismdashunclear Autoregulatory Failure

Normal autoregulation maintains constant cerebral blood flow over range of systemic BP by arteriolar constriction and dilatation

As upper limits of cerebral autoregulation exceeded arterioles dilate and cerebral blood flow increases Results in brain hyperperfusion and may lead to breakdown of BBB

Chronic HTN Vascular changes ldquoresetrdquo range of autoregulation As a result pts with PRES in setting of longstanding HTN

may have markedly elevated BP while less severe elevations even nl BP are associated with PRES in other settings

PRES

Pathogenesismdashunclear Endothelial dysfunction

Cytotoxic therapies may have direct toxicity on vascular endothelium leading to

capillary leakage and BBB with axonal swelling triggering vasogenic edema

may occur in normotensive individuals with nontoxic levels of these drugs

Preeclampsia PRES best dx by elevated markers

Elevated endothelial cell markers fibronectin tPA thrombomodulin endothelin-1 von Willebrand factor Markers also elevated in PRES associated with chronic renal

failure lupus nephritis HUS

Other possible causes uremia sepsis hypomagnesemia fluid overload

PRES

Anatomy Combination of acute HTN and endothelial damage

results in hydrostatic edema (type of vasogenic edema characterized by forced leakage of serum through capillary walls and into the brain interstitium)

The cortex structurally more tightly packed than the white matter resists accumulation of edema hence predilection of abnormalities in white matter

Primary involvement of posterior brain regions not well understood (One thought is regional heterogeneity of sympathetic nerve innervation of intracranial arterioles which protects the brain from marked increases in BP have greater concentration around pial and intracerebral vessels in anterior cirulation)

PRES

Associated Conditions Comorbidities that exacerbate neurologic deterioration ischemic bowel disease sepsis hyponatremia fever proteinuria

Hypertensive Encephalopathy PRES likely caused by vasogenic edema from

breakthrough of autoregulation Risk for HE rapidly developing fluctuating or

intermittent hypertension May be seen in pts with chronic HTN renal failure or

preeclampsia-eclampsia Percent elevation of BP above baseline as well as

severity of HTN are associated with development of PRES Therefore it may occur in normotensive pts

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

PRES

A clinical radiologic syndrome of heterogenic etiologies

Many Names Posterior Reversible Encephalopathy Syndrome (PRES)

Reversible Posterior Cerebral Edema Syndrome

Posterior Leukoencephalopathy Syndrome

Hyperperfusion Encephalopathy

Brain Capillary Leak Syndrome

PRES

Epidemiology All age groups susceptible (ages 2-90)

More common in women even when eclampsia excluded

Risk Factors

Hypertensive disorders

Renal disease

Immunosuppressive therapies

PRES

Pathogenesismdashunclear Autoregulatory Failure

Normal autoregulation maintains constant cerebral blood flow over range of systemic BP by arteriolar constriction and dilatation

As upper limits of cerebral autoregulation exceeded arterioles dilate and cerebral blood flow increases Results in brain hyperperfusion and may lead to breakdown of BBB

Chronic HTN Vascular changes ldquoresetrdquo range of autoregulation As a result pts with PRES in setting of longstanding HTN

may have markedly elevated BP while less severe elevations even nl BP are associated with PRES in other settings

PRES

Pathogenesismdashunclear Endothelial dysfunction

Cytotoxic therapies may have direct toxicity on vascular endothelium leading to

capillary leakage and BBB with axonal swelling triggering vasogenic edema

may occur in normotensive individuals with nontoxic levels of these drugs

Preeclampsia PRES best dx by elevated markers

Elevated endothelial cell markers fibronectin tPA thrombomodulin endothelin-1 von Willebrand factor Markers also elevated in PRES associated with chronic renal

failure lupus nephritis HUS

Other possible causes uremia sepsis hypomagnesemia fluid overload

PRES

Anatomy Combination of acute HTN and endothelial damage

results in hydrostatic edema (type of vasogenic edema characterized by forced leakage of serum through capillary walls and into the brain interstitium)

The cortex structurally more tightly packed than the white matter resists accumulation of edema hence predilection of abnormalities in white matter

Primary involvement of posterior brain regions not well understood (One thought is regional heterogeneity of sympathetic nerve innervation of intracranial arterioles which protects the brain from marked increases in BP have greater concentration around pial and intracerebral vessels in anterior cirulation)

PRES

Associated Conditions Comorbidities that exacerbate neurologic deterioration ischemic bowel disease sepsis hyponatremia fever proteinuria

Hypertensive Encephalopathy PRES likely caused by vasogenic edema from

breakthrough of autoregulation Risk for HE rapidly developing fluctuating or

intermittent hypertension May be seen in pts with chronic HTN renal failure or

preeclampsia-eclampsia Percent elevation of BP above baseline as well as

severity of HTN are associated with development of PRES Therefore it may occur in normotensive pts

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

PRES

Epidemiology All age groups susceptible (ages 2-90)

More common in women even when eclampsia excluded

Risk Factors

Hypertensive disorders

Renal disease

Immunosuppressive therapies

PRES

Pathogenesismdashunclear Autoregulatory Failure

Normal autoregulation maintains constant cerebral blood flow over range of systemic BP by arteriolar constriction and dilatation

As upper limits of cerebral autoregulation exceeded arterioles dilate and cerebral blood flow increases Results in brain hyperperfusion and may lead to breakdown of BBB

Chronic HTN Vascular changes ldquoresetrdquo range of autoregulation As a result pts with PRES in setting of longstanding HTN

may have markedly elevated BP while less severe elevations even nl BP are associated with PRES in other settings

PRES

Pathogenesismdashunclear Endothelial dysfunction

Cytotoxic therapies may have direct toxicity on vascular endothelium leading to

capillary leakage and BBB with axonal swelling triggering vasogenic edema

may occur in normotensive individuals with nontoxic levels of these drugs

Preeclampsia PRES best dx by elevated markers

Elevated endothelial cell markers fibronectin tPA thrombomodulin endothelin-1 von Willebrand factor Markers also elevated in PRES associated with chronic renal

failure lupus nephritis HUS

Other possible causes uremia sepsis hypomagnesemia fluid overload

PRES

Anatomy Combination of acute HTN and endothelial damage

results in hydrostatic edema (type of vasogenic edema characterized by forced leakage of serum through capillary walls and into the brain interstitium)

The cortex structurally more tightly packed than the white matter resists accumulation of edema hence predilection of abnormalities in white matter

Primary involvement of posterior brain regions not well understood (One thought is regional heterogeneity of sympathetic nerve innervation of intracranial arterioles which protects the brain from marked increases in BP have greater concentration around pial and intracerebral vessels in anterior cirulation)

PRES

Associated Conditions Comorbidities that exacerbate neurologic deterioration ischemic bowel disease sepsis hyponatremia fever proteinuria

Hypertensive Encephalopathy PRES likely caused by vasogenic edema from

breakthrough of autoregulation Risk for HE rapidly developing fluctuating or

intermittent hypertension May be seen in pts with chronic HTN renal failure or

preeclampsia-eclampsia Percent elevation of BP above baseline as well as

severity of HTN are associated with development of PRES Therefore it may occur in normotensive pts

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

PRES

Pathogenesismdashunclear Autoregulatory Failure

Normal autoregulation maintains constant cerebral blood flow over range of systemic BP by arteriolar constriction and dilatation

As upper limits of cerebral autoregulation exceeded arterioles dilate and cerebral blood flow increases Results in brain hyperperfusion and may lead to breakdown of BBB

Chronic HTN Vascular changes ldquoresetrdquo range of autoregulation As a result pts with PRES in setting of longstanding HTN

may have markedly elevated BP while less severe elevations even nl BP are associated with PRES in other settings

PRES

Pathogenesismdashunclear Endothelial dysfunction

Cytotoxic therapies may have direct toxicity on vascular endothelium leading to

capillary leakage and BBB with axonal swelling triggering vasogenic edema

may occur in normotensive individuals with nontoxic levels of these drugs

Preeclampsia PRES best dx by elevated markers

Elevated endothelial cell markers fibronectin tPA thrombomodulin endothelin-1 von Willebrand factor Markers also elevated in PRES associated with chronic renal

failure lupus nephritis HUS

Other possible causes uremia sepsis hypomagnesemia fluid overload

PRES

Anatomy Combination of acute HTN and endothelial damage

results in hydrostatic edema (type of vasogenic edema characterized by forced leakage of serum through capillary walls and into the brain interstitium)

The cortex structurally more tightly packed than the white matter resists accumulation of edema hence predilection of abnormalities in white matter

Primary involvement of posterior brain regions not well understood (One thought is regional heterogeneity of sympathetic nerve innervation of intracranial arterioles which protects the brain from marked increases in BP have greater concentration around pial and intracerebral vessels in anterior cirulation)

PRES

Associated Conditions Comorbidities that exacerbate neurologic deterioration ischemic bowel disease sepsis hyponatremia fever proteinuria

Hypertensive Encephalopathy PRES likely caused by vasogenic edema from

breakthrough of autoregulation Risk for HE rapidly developing fluctuating or

intermittent hypertension May be seen in pts with chronic HTN renal failure or

preeclampsia-eclampsia Percent elevation of BP above baseline as well as

severity of HTN are associated with development of PRES Therefore it may occur in normotensive pts

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

PRES

Pathogenesismdashunclear Endothelial dysfunction

Cytotoxic therapies may have direct toxicity on vascular endothelium leading to

capillary leakage and BBB with axonal swelling triggering vasogenic edema

may occur in normotensive individuals with nontoxic levels of these drugs

Preeclampsia PRES best dx by elevated markers

Elevated endothelial cell markers fibronectin tPA thrombomodulin endothelin-1 von Willebrand factor Markers also elevated in PRES associated with chronic renal

failure lupus nephritis HUS

Other possible causes uremia sepsis hypomagnesemia fluid overload

PRES

Anatomy Combination of acute HTN and endothelial damage

results in hydrostatic edema (type of vasogenic edema characterized by forced leakage of serum through capillary walls and into the brain interstitium)

The cortex structurally more tightly packed than the white matter resists accumulation of edema hence predilection of abnormalities in white matter

Primary involvement of posterior brain regions not well understood (One thought is regional heterogeneity of sympathetic nerve innervation of intracranial arterioles which protects the brain from marked increases in BP have greater concentration around pial and intracerebral vessels in anterior cirulation)

PRES

Associated Conditions Comorbidities that exacerbate neurologic deterioration ischemic bowel disease sepsis hyponatremia fever proteinuria

Hypertensive Encephalopathy PRES likely caused by vasogenic edema from

breakthrough of autoregulation Risk for HE rapidly developing fluctuating or

intermittent hypertension May be seen in pts with chronic HTN renal failure or

preeclampsia-eclampsia Percent elevation of BP above baseline as well as

severity of HTN are associated with development of PRES Therefore it may occur in normotensive pts

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

PRES

Anatomy Combination of acute HTN and endothelial damage

results in hydrostatic edema (type of vasogenic edema characterized by forced leakage of serum through capillary walls and into the brain interstitium)

The cortex structurally more tightly packed than the white matter resists accumulation of edema hence predilection of abnormalities in white matter

Primary involvement of posterior brain regions not well understood (One thought is regional heterogeneity of sympathetic nerve innervation of intracranial arterioles which protects the brain from marked increases in BP have greater concentration around pial and intracerebral vessels in anterior cirulation)

PRES

Associated Conditions Comorbidities that exacerbate neurologic deterioration ischemic bowel disease sepsis hyponatremia fever proteinuria

Hypertensive Encephalopathy PRES likely caused by vasogenic edema from

breakthrough of autoregulation Risk for HE rapidly developing fluctuating or

intermittent hypertension May be seen in pts with chronic HTN renal failure or

preeclampsia-eclampsia Percent elevation of BP above baseline as well as

severity of HTN are associated with development of PRES Therefore it may occur in normotensive pts

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

PRES

Associated Conditions Comorbidities that exacerbate neurologic deterioration ischemic bowel disease sepsis hyponatremia fever proteinuria

Hypertensive Encephalopathy PRES likely caused by vasogenic edema from

breakthrough of autoregulation Risk for HE rapidly developing fluctuating or

intermittent hypertension May be seen in pts with chronic HTN renal failure or

preeclampsia-eclampsia Percent elevation of BP above baseline as well as

severity of HTN are associated with development of PRES Therefore it may occur in normotensive pts

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

PRES

Associated Conditions Immunosuppresive Therapy

Toxic levels of meds NOT required for development of PRES and prior Rx exposure does NOT appear to be protective

Cyclosporine Exacerbates HTN by inhibiting nitric oxide production and

thought to mediate cellular injury through mitochondrial dysfunction

Systemic HTN was only major factor associated with neurotoxic effects (MAHA thrombocytopenia and hypoalbuminemia were common thought)

Elevated levels NOT related to onset of neurologic sx Other Rx Tacrolimus Sirolimus Cisplatin Interferon

therapies Bevacizumab

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

PRES

CLINICAL MANIFESTATIONS Headache

Typically constant nonlocalized mod to sev unresponsive to analgesia Altered Consciousness

Ranged from mild somnolence to confusion and agitation progressing to stupor or coma

Seizures Usually generalized tonic clonic May begin focally and often recur Status

epilepticus has been reported Preceding visual losshallucinations suggest occipital lobe origin

Minority of pts may be seizure free Visual Distubances

Hemianopia visual neglect auras visual hallucinations cortical blindness Cortical blindness may be associated with denial of blindness (Antonrsquos

syndrome) Fundoscopic exam often normal May find papilledema with accompanying

flame-shaped retinal hemorrhages or exudates Other findings

DTR may be brisk with Babinski signs present HTN is frequent but not invariable The hypertensive crisis may precede the

neurologic syndrome by 24h or longer

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

PRES

DDx Stroke Venous thrombosis Toxic or metabolic encephalopathy Demyelinating disorders Vasculitis Bilateral posterior cerebral a infarctions (ldquotop of the Basilar syndromerdquo)

Encephalitis

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

PRES

Neuroimaging Symmetrical white matter edema in posterior cerebral

hemispheres particularly in parieto-occipital regions

With tx resolution of findings expected within days to weeks

Important localizations Calcarine and paramedian parts of occipital lobe are usually

spared this distinguishes PRES from bilat post cerebral a infarcts

Involvement of cerebellum and brainstem is common

Lesions are usually in anterior cortex occur in more severe cases

Although abnormalities primarily affect subcortical white matter cortex and basal ganglia may be involved

Distribution is NOT usually confined to a single vascular territory

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

PRES

Neuroimaging 2 FLAIR sequences improve sensitivity and detect subtle peripheral lesions

Gyriform signal enhancement reflecting disruption of BBB can be present following administration of gadolinium

Petechial and large parenchymal hemorrhages have been described

DWI aids to distinguish PRES from a top of the basilar stroke

The anatomical extent of MRI findings have been shown to correlate with patient outcome

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

PRES

Gyriform enhancement

Resolution after 2 weeks

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

PRES

Treatment HTN

Lower diastolic BP to 100-105 mmHg within 2-6 hrs Max initial fall of BP should not exceed 25 of presenting value

More aggressive tx may reduce beyond autoregulatory range and possibly lead to ischemic event

Use of IV Labetalol or Nicardipine to attain desired BP If neither agent effective may consider nitroprusside with caveat of theoretical concern of paradoxically increasing intracranial pressure through vasodilatation

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

PRES

Treatment Seizures Phenytoin

Can probably be safely tapered as sx and neuroimaging findings resolve usually after 1-2 wks

In setting of eclampsia Delivery of baby and placenta are usually sufficient but if not tx with Mg as opposed to Phenytoin or Diazepam

No indication pts at long-term risk for sz recurrence or epilepsy (although long term studies are lacking)

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

PRES

Treatment Cytotoxic Immunosuppressive Therapy

Reduce dose or remove agent Not recommended that agents known to induce PRES be

reintroduced In setting of cytotoxic agent pt with one or more are

at risk for PRES (based on 2 case studies and lit review) Significant fluid overload (gt10 baseline weight) Mean BP gt25 baseline Cr gt18 mgdL

Note Decadron NOT recommended given associated risk of HTN fluid overload and electrolyte disturbance

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

PRES

Prognosis Death may result from progressive cerebral edema intracerebral hemorrhage or as complication of underlying condition

In one series elev Cr levels were a risk factor for death but neither BP levels or percent elevation from baseline values appeared to correlate with prognosis

More extensive brain involvement particularly in brainstem correlates with worse prognosis

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008

Bibliography

Reversible Posterior Leukoencephalopathy Syndrome wwwuptodatecom 14 July 2008