This is your brain, on drugs.

Justin Brucker, MD (jbrucker@uwhealth.org)Tabassum Kennedy, MD

Aaron Field, MD

eEdE-04

University of Wisconsin, Madison

T2 fat satT2 FLAIRT1Path 3D

INTRODUCTION: “There’s more than one way to fry an egg.”

In keeping with modern medical practices, there is an increasing trend to rely heavily upon neuroimaging as the primary diagnostic tool -- especially when clinicians are faced with a patient that is either medically complex, or presenting with nonspecific neurologic findings (e.g. “altered mental status”).

Many of these patients have a history of long term pharmaceutical and/or non-pharmaceutical drug use, which may further complicate interpretation of their scans.

We divide our cases into 3 general categories:

1. Unintended adverse effects of therapeutic agents (over-dosage and regular use)

2. Known side effects of chemotoxic agents (i.e. chemotherapy)

3. Known consequences of non-pharmaceutical agents (illicit drugs and poisons)

This purpose of this exhibit is to showcase the wide range neuroradiologic manifestations that arise from the use of various chemical agents, with emphasis on salient imaging and clinical features.

MENU: Click to jump to a topic

1. UNINTENDED ADVERSE EFFECTS OF THERAPEUTIC AGENTS

2. CHEMOTHERAPEUTIC SIDE EFFECTS

3. ILLICIT/RECREATIONAL DRUGS & POISONS

Propofol HyperoxygenationGadolinium Osmotic Myelinolysis

BevacizumabTemozolomideLevetiracetam

PhenytoinIRIS

HyperinsulinemiaHypervitaminosis

Ipilimumab Methotrexate Cyclophosphamide Capecitabine

Pazopanib Cyclosporin Tacrolimus

Cocaine Heroin Oxycontin Benzodiazepine

Delayed Reversible Hypoxic Leukoencephalopathy Carbon MonoxideEthylene Glycol

Marchifava-Bignami Disease

Metronidazole

1. UNINTENDED ADVERSE EFFECTS OF THERAPEUTIC AGENTS

In this section, we visit the imaging findings associated with the use of various pharmaceutical agents.

In some cases, imaging abnormalities are secondary to overutilization or overdosage, although signal abnormalities can also be encountered with normal intended use.

These findings have to potential to mimic or mask pathologic conditions, or to denote true drug-related CNS toxicity.

PropofolT2 FLAIR

T2 FLAIR

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Top Images: Imaging obtained with patient on a propofol drip.

There is loss of CSF nullification on T2 FLAIR-weighted imaging is noted along the cerebral sulci (), interpeduncular cistern (), and cisterna magna ().

Bottom Images:These findings have resolved on the short-term interval follow-up study.

The therapeutic and imaging mechanisms of propofol are not completely understood, but may involve potentiation of GABAergic chloride channels and blockage of voltage-gated sodium channels.

It is a lipophilic anesthetic/hypnotic agent that can cross the blood-brain barrier, often used as a sedative for short-term procedures.

Intrinsically fast longitudinal (T1) recovery, increased membrane permeability, increased cerebral vascularity, and protein interactions have all been proposed as possible causes of propofol-related CSF signal changes on T2 FLAIR weighted imaging.

Retained Gadolinium

T2 FLAIR T1

Confluent areas of marked T2 FLAIR enhancement of the CSF along the cerebral convexities ().

Subtle foci of T1-hyperintensity are noted along the leptomeningeal margins (), compatible with retained gadolinium-based contrast.

History: Noncontrast head MRI performed 1-day after contrast-enhanced cardiac MRI in an elderly patient with chronic renal insufficiency.

Gadolinium-based contrast agents (GBCAs) are paramagnetic; gadolinium has 7 unpaired electrons, which induce a relatively large magnetic moment that is several hundred times stronger than a proton’s, when exposed to a strong magnetic field (B0).

GBCAs shorten the T1 and T2 relaxivities of surrounding protons via electron-dipole interactions, thereby hastening spin-lattice and spin-spin energy exchanges.

Shorter T1 relaxation times means faster longitudinal relaxation (T1 hyperintensity), as well as faster inversion recovery; CSF will not appear nullified on T2 FLAIR imaging that is obtained with a standard inversion time (TI).

HyperoxygenationT2 FLAIR

case courtesy of Mark Tierney

Stippled and linear areas of T2 FLAIR signal intensity is noted along the cerebral convexities (), denoting impaired CSF nullification.

Exuberant administration of supplemental oxygen (as with this patient who inadvertently received 100% FiO2) results in a larger percentage of soluble molecular O2 within the blood pool, as opposed to hemoglobin-bound.

Molecular O2 is paramagnetic and therefore results in T1 and T2 shortening effects -- similar to gadolinium and [theoretically] propofol – however, stippled hyperintensity that stays close to the pial margins is more typical for hyperoxygenation effects on T2 FLAIR. The differential includes leptomeningeal carcinomatosis and infection.

Long term effects of prolonged hyperoxygenation (FiO2 > 50%) include direct cytotoxic injury to neurons, retina, and alveoli, secondary to the presence of oxygen reactive species and free radical cascades.

Central Pontine Osmotic Myelinolysis

T2T2 FLAIR DWI ADC

Confluent areas of T2 and T2 FLAIR hyperintensity with associated restricted diffusion throughout the central pons (), with relative sparing of the peripheral fibers and pyramidal tracts ().

History: 50-year-old intoxicated male who initially presented with hyponatremia, now with spastic quadriparesis and poor neurologic response, status post administration of intravenous fluids.

Osmotic myelinolysis is a dreaded consequence of overly rapid correction of low serum sodium levels.

In patients who has adjusted to a chronically hyponatremic state, introduction of relatively hypertonic extracellular environment creates a severe intracellular-extracellular osmotic gradient. Water is forcibly pulled out of the cells (oligodendrocytes are preferentially affected), resulting in membrane lysis, vacuolization, and demyelination.

Extrapontine osmotic myelinolysis can also accur, sparing the pons, but affecting the basal ganglia, corpus callosum and descending corticoscpinal tracts.

Hyperinsulinemia/HypoglycemiaT1

T2 FLAIRMultiplanar, multisequence images demonstrated areas of intrinsic T1 and T2 FLAIR hyperintensity throughout the basal ganglia (), retrolenticular internal capsules (), subthalamic nuclei (), and hippocampal formations ().

case courtesy of Howard Rowley

Profound hypoglycemia can be encountered in the setting of overadministration of exogenous insulin and sulfonylureas (Metformin), or occasionally in the setting of insulinoma.

Although marked T2 hyperintensity of the basal ganglia is well-associated with hypoglycemia, this is an unusual case with associated T1 hyperintensity, possibly reflecting superimposed anoxic injury and/or early necrosis.

HypervitaminosisT2 DWIT2*

T2 T2*

2011

2015

Susceptiility-related hypointensity noted throughout the lentiform nuclei (top images; ), in this patient taking large quantities of multivitamin with mineral supplement. After cessation of multivitamin use, the findings have intervally normalized (bottom images).

Multivitamins and other nutritional supplements often contain larger-than-needed quantities of fat soluble vitamins (A, D, E, & K) and minerals, which have a tendency to accumulate within the body over time with heavy usage. Eat vegetables, instead.

Metronidazole Induced Encephalopathy (1/3)

T2 FLAIR

T2 FLAIR

DWI

ADC

splenium

dentate nucleiinferior colliculi

Focal T2 FLAIR hyperintensity is noted within the dentate nuclei, inferior colliculi, and splenium (as labeled).

Of note, there is restricted diffusion within the splenial lesion, which raises concern of an additional component of cytotoxic edema.

History: New onset encephalopathy in patient being treated for Clostridium difficile colitis.

centromedian thalamic nuclei

red nuclei

inferior colliculi

dentate nuclei

Metronidazole Induced Encephalopathy (2/3)

Before

After (1 month)

Left Side and Top Right Images:Although the splenium is spared, there is notable involvement of the centromedian thalamic nuclei (), red nuclei (), inferior colliculi (), and dentate nuclei ().

These findings were resolved after cessation of metronidazole, and supplemtation of thiramine and folate (Bottom Right Image).

History: Encephalopathy and seizures in a patient being treated for severe acute bacterial sinusitis.

Metronidazole (Flagyl) is a mainstay antibiotic for the treatment of obligate anaerobic bacterial infections.

These microbes reduce the metronidazole into its active form via the pyruvate:ferredoxin oxioreductase pathway.

This active form then covalently binds to the microbial DNA and subsequently inhibits DNA synthesis.

T2 FLAIRT2 FLAIR

Metronidazole Induced Encephalopathy (3/3)

dentate nucleus

red nucleus

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The pathophysiology of Flagyl-related neurotoxicity are not completely understood.

However, multiple mechanisms have been proposed, such as: binding of nucleic acid moeities, axonal and Purkinje cell swelling, and interference of GABA-receptor binding.

These effects are typically reversible upon cessation of the drug and supplementation with thiamine and folate.

Wernicke’s encephalopathy can be a radiologic and clinical mimic of metronidazole induced encephalopathy, especially when one considers that the toxic effects of metronidazole are potentiated by liver disease and alcohol consumption.

The Guillan-Mollaret Triangle

The Guillain-Mollaret Triangle can be affected by metronidazole toxicity:Also known as the dentato-rubro-olivary triangle, it is comprised of a set of efferent pathways connecting the:

1. Dentate nucleus contralateral red nucleus, via superior cerebellar peduncle fibers.

2. Red nucleus ipsilateral inferior olive, via the central tegmental tract.

3. Inferior olive contralateral dentate nucleus, via inferior cerebellar peduncle fibers.

Involvement of the first 2 arms of the triangle can lead to hypertrophic olivary degeneration, with symptoms including ataxia and palatal myoclonus.

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Levetiracetam Toxicity

T2 FLAIR DWI ADC

History: Altered mental status in an inpatient being treated with Keppra for worsening seizures.

Small irregular focus of T2 FLAIR hyperintensity within the splenium of the corpus callosum (), with subtle restricted diffusion ().

Signal abnormalities within the splenium of the corpus callosum is encountered in a wide variety of toxic, metabolic, and other inflammatory CNS conditions.

The differential includes metronidazole toxicity, antiepileptic drug overdose, extrapontine myelinolysis, viral infections, multiple sclerosis and ADEM, Marchifava-Bignami disease, and hypoglycemia.

Phenytoin

T2 FLAIR

CT

T1

Multiplanar, multisequence demonstrate marked diffuse atrophy of the cerebellar hemispheres and vermis ().

There is also marked hyperostosis of the calvarium evident on T1 weighted and CT imaging ().

Phenytoin (Dilantin) mediates blockage of voltage-gated sodium channels.

Even at therapeutic doses, chronic usage is associated with cerebellar atrophy, as well as a wide range of other systemic manifestations (hyperostosis and osteopenia, gingival hypertrophy, hypertrichosis, anemia, and drug-induced lupus.

case courtesy of Lindell Gentry

Immune Reconstitution Inflammatory Syndrome

T1+CT2 FLAIR

History: 49-year-old female with history of HIV.

Multiplanar T2 FLAIR weighted images demonstrate asymmetric confluent areas of hyperintense signal change throughout the bifrontal white amtter ().

There is an associated cavitary lesion within the left frontal lobe, with small amount of peripheral nodular enhancement ().

• T cell mediated encephalitis occurs in the setting of HIV/autoimmune disease• Occurs when restored immunity causes an exaggerated immune response to infectious/non infectious antigens• Low CD4 count (<50 cells/μL) is a risk factor

Unmasking IRIS:• Antiretrovirals Rx unmask a subclinical undiagnosed opportunistic infection. Tissue damage by pathogen

and immune response.Paradoxical IRIS:

• Patient deteriorates despite successful treatment of opportunistic infection. Tissue damage by immune response to antigens

Temozolomide & Glioma Pseudoprogression

T2 FLAIR T1+C CBV

case courtesy of Howard Rowley

There is a large area of confluent T2 FLAIR hyperintensity throughout the right frontal white matter (), surrounding a T2 hypointense mass lesion () that demonstrates marked peripheral enhancement (). These findings were noted to be increased from prior imaging (not shown) and therefore initially concerning for tumor progression. However, corresponding cerebral blood volume (CBV) map demonstrates the lesion to be non-hyperemic ().

History of high-grade glioma, status post chemoradiation therapy.

Temozolomide is a purine-methylating agent, which adds a methyl group to guanine and adenine derived bases, thereby inhibiting DNA synthesis. Its action is counteracted by the enzyme methylguanine methyltransferase (MGMT), but this enzyme can in turn be inhibited by methylation (“MGMT-methylated tumor status”).

Pseudoprogression mimics apparent increased size and enhancement of the tumor bed, but can actually denote a more favorable prognosis. It is more common in MGMT-methylated tumors, usually 1-3 months after chemoradiation therapy that utilizes temozolomide. Decreased CBV is an important distinguishing feature of pseudoprogression.

Bevacizumab and Pseudoresponse vs. Pseudoinfarction

T1+C DWI ADC

T1+C DWI ADC

Baseline

After Treatmentcase courtesy of Howard Rowley

Initial baseline images demonstrate enhancing tumor within the posterior right subinsular white matter (), although with intermediate diffusion characteristics on DWI/ADC ().

On follow-up imaging – after initiation of Avastin -- there appears to be decreased enhancement (), but there is markedly increased restricted diffusion in the tumor bed ().

History of high-grade glioma, with recent evidence of progression

Bevacizumab (Avastin) is an anti-VEGF-A (vascular endothelial growth factor A) monoclonal antibody that intercepts the protein before it can bind to the VEGF-receptor.

This results in decreased angiogenesis and vascularity, which can reduce the apparent size and enhancement of a tumor.

Avastin Related Hypoenhancement

T1+CT2 T2 FLAIR

History: 40-year-old female with widely metastatic ovarian cancer.

Large metastatic mass lesion centered in the left basal ganglia with intermediate T2 () and T2 FLAIR signal intensity (). There is notable absence of perilesional vasogenic edema, as well as little to no postcontrast enhancement (), which are considered out of proportion to the size of the mass.

Bevacizumab is utilized in the treatment of various malignancies, including ovarian cancer, lung cancer, renal cancer, breast cancer, and colorectal cancer.

Poor tumoral enhancement while on Avastin should be interpreted with caution, as actual progression can be masked.

2. CHEMOTHERAPEUTIC SIDE EFFECTS

Chemopharmaceuticals are often toxic by nature, intended to inhibit cellular growth and division in highly proliferative tissues, or significantly alter the patient’s immune system.

Although side effects related to chemotherapy are not intended, they are not unexpected.

The CNS imaging features of various chemotoxic agents often overlap, although several medications are associated with more specific radiologic findings.

Ipilimumab Hypophysitis

T1 T1+C T2 FLAIR

History: 65-year-old female with history of metastatic melanoma.

Top images: Mass-like enlargement and peripheral enhancement of the pituitary gland and stalk () are noted at presentation.Bottom Images: Findings show marked improvement (), 2 months after cessation of ipilimumab.

Ipilimumab is a monoclonal antibody that binds to cytotoxic T-lymphocyte antigen 4 (CTLA-4), thereby inhibiting the immunosuppressive effects of CTLA-4 . Unfortunately, CTLA-4 is also present in normal pituitary tissue, allowing for immune-mediated cross-reactivity.

The imaging and clinical features can mimic pituitary apoplexy, metastatic disease, or other forms of hypophysitis. Treatment often involves hormonal replacement and cessation of Ipilimumab.

At presentation

2 months later

Methotrexate Toxicity (Case #1)

T2 FLAIR

DWI

ADC

Multifocal areas of patchy T2 FLAIR hyperintensity and restricted diffusion are scattered throughout the periatrial and biparietal white matter () as well as the splenium of the corpus callosum ().

Methotrexate is a competitive inhibitor of dihydrofolate reductase, effectively blocking the pathway for conversion of folate into nucleic acid precursors. It is often used in the treatment of lymphoma and leukemia.

Methotrexate Toxicity (Case #2)

T2 DWI ADC

Focal T2 hyperintense signal changes and restricted diffusion are noted within the lateral margin of the right centum semiovale () and splenium of the corpus callosum ().

An example of intrathecal methotrexate use for the treatment of acute lymphoblastic leukemia.

Signal abnormalities within the centrum semiovale and splenium are often reported, and can be rather transitory and migratory; short term interval follow-up often demonstrates interval resolution or redistribution of signal abnormalities to different portions of the cerebral white matter.

Methotrexate Toxicity (Case #3)

T2 FLAIR

Large, symmetric, confluent T2 FLAIR hyperintense signal changes are seen throughout the majority of the cerebral white matter (), with relative sparing of the subcortical U-fibers, and notable involvement of the internal capsules.

More extensive white matter toxicity related to methotrexate use have been reported with an intrathecal route of delivery, younger age at the time of therapy, and combination with radiation therapy.

The neurotoxicity effects can have delayed onset, as with this patient who presented with confusion and seizures several weeks after treatment.

Cyclophosphamide

T2 FLAIR

Multiplanar T2 FLAIR images demonstrate symmetric patchy areas of hyperintense signal change within the bilateral periatrial white matter (), with indistinct borders that spare the subcortical U-fibers.

Cyclophosphamide is an alkylating agent that specifically alkylates guanine, thereby interference with DNA synthesis.

It is used in the treatment of various malignancies, including lymphoma, leukemia, and several primary CNS neoplasms.

History: Long-term follow-up in a patient previously treated for lymphoma.

CapecitabineT2 FLAIR

T1+C

Diffuse smooth pachymeningeal thickening is noted throughout the dural convexities on T2 FLAIR () and postcontrast T1-weighted () imaging, in this patient with confusion and lethargy, being treated for intestinal cancer.

Capecitabine is the oral prodrug of 5-fluorouracil (5FU), which undergoes a 3-step enzymatic conversion to its active form. The third step is catalyzed by thymidine phosphorylase, which is present in tumoral tissues and normal hepatocytes. Detoxification of 5FU is mediated by dihydropyrimidine dehydrogenase, which is absent in 2-4% of the patient population; the toxic effects of capecitabine are therefore potentiated in these individuals.

In addition to white matter T2 FLAIR changes similar to methotrexate toxicity, idiopathic intracranial hypotension with associated dural thickening has been reported with capecitabine toxicity.

Pazopanib -- Posterior Reversible Encephalopathy Syndrome

T2 FLAIR

T2 FLAIR

Presentation

1 month later

Top Images: Multifocal areas of cortical and subcortical T2 FLAIR hyperintensity (), scattered along the posterior cerebral margins.

Bottom Images: Findings have resolved on short-term interval follow-up, after cessation of pazopanib

Pazopanib is a tyrosine kinase inhibitor that has multiple molecular targets (including VEGF-R), resulting in inhibition of tumor growth and angiogenesis.

It is used in the treatment of renal cell carcinoma and various sarcomas.

History: Altered mental status in a patient being treated for renal cell carcinoma.

Cyclosporine Induced PRES

T2 FLAIRT2

Asymmetric areas of slightly expansile T2 and T2 FLAIR hyperintensity coursing along the parieto-occipital white matter and cortical ribbon (), consistent with PRES.

History: Status post renal transplant, now with seizures and confusion

Cyclosporine is a cyclic peptide that inhibits T-cell growth and interleukin-2 transcription via a complex set of interactions with the calcineurin-mediated signaling pathway. It is used as an immunosuppressive agent in the setting of organ transplantation. It has been reported with wide variety of systemic side effects, including PRES, presumably by disrupted autoregulation of cerebrovascular tone.

Tacrolimus Induced PRES (Case #1)

T2 FLAIR T2 FLAIR

Asymmetric areas of slightly expansile T2 and T2 FLAIR hyperintensity coursing along the parieto-occipital white matter and cortical ribbon (), that resolved on follow-up imaging (right most image), consistent with PRES.

Presentation 1 month later

Tacrolimus (Prograf) is a macrolide lactone inhibitor of the calcineruin signaling pathway in T-cell lymphocytes, resulting in decreased IL-2 transcription and lowered T-cell activity.

It has been associated with PRES, electrolyte/metabolic derangement, hypertension, nephrotoxicity, liver disease, skin disorders, and non-Hodgkins lymphoma.

In immunosuppressed patients, the differential includes viral infection, progressive multifocal leukoencephalopathy, and acute disseminated encephalomyelitis.

Tacrolimus Induced PRES (Case #2)T2 T2Before After

Patchy areas of T2 hyperintense signal are noted throughout the central pontine belly and pontine tegmentum (), which resolves on follow-up imaging (right image) after correction of hypertension was achieved.

Posterior reversible encephalopathy syndrome (a.k.a. reversible posterior leukoencephalopathy syndrome) has a predilection for the posterior cerebral white matter, but can also involve the cortical ribbon, basal nuclei, and brainstem. Patchy postcontrast enhancement can also be an associated finding.

3. ILLICIT/RECREATIONAL DRUGS & POISONS

In our last section, we will visit the imaging findings associated with recreational drug use, alcohol consumption, and exposure to non-pharmacologic toxins.

Unfortunately, many of these uncontrolled substances are highly addictive, inconsistently prepared, and/or contain toxic additives – this can worsen clinical outcomes and confound the radiologic presentation.

Cocaine Induced PRES

T2

T2 FLAIR T1+C

Symmetric areas of expansile confluent T2 hyperintensity are noted throughout the bilateral peri-Rolandic white matter ().

There is associated T2 FLAIR hyperintensity that involves the overlying cortical ribbon (), as well as robust postcontrast enhancement ().

Cocaine is a highly addictive tropane alkyloid derived from the coca plant.

In the CNS, it acts primarily as a potent sympathomimetic, by inhibiting reuptake of synaptic serotonin, dopamine, and catecholamines.

It can lead to severe hypertension and tachycardia, as well as vasospasm and prothrombotic effects throughout the cerebrovascular system.

More Cocaine, with Hemorrhage and Aneurysm

CT TOF MRA

Spontaneous intraparenchymal hematoma with peri-hemorrhagic edema (), in this patient with cocaine induced hypertension.

3D time-of-flight MRA acquisition demonstrates a large aneurysm projecting posterolaterally off of the proximal left cavernous internal carotid artery ().

Consequences of cocaine intake include intracranial hemorrhage, stroke, aneurysm formation, moyamoya, vasculitis, and chronic cerebral atrophy.

Inhalational Heroin Leukoencephalopathy

ADC

T2T2 FLAIR

DWI

History: Found down, after “chasing the dragon.”

Patchy, symmetric areas of T2 hyperintensity and restricted diffusion are noted within the posterior centrum semiovale () and splenium of the corpus callosum ().

Heroin is an extremely addictive recreational opiate, which exerts its effect by binding μ-opioid receptors throughout the CNS and cerebrovascular system.

It is usually either injected intravenously, or the vapors are inhaled as the heroin is heated over metal foil; the heated heroin adopts a flowing serpiginous appearance, hence referred to “chasing the dragon.”

More “Chasing the Dragon”

CT T2 DWI ADC

Consequences of heroin use include stroke and cytotoxic edema, secondary to a combination of: vasospasm, vasculitis, suppressed central respiratory drive, and decreased cardiovascular tone.

Inhalation of heated heroin vapor is suspected to confer additional toxic effect, possibly secondary to the presence of lipophilic additives and impurities, which may either be used to cut the heroin or the product of the heating process.

Large areas of confluent expansile edema replacing the near-entirety of the centrum semiovale, with associated restricted diffusion and relative sparing of the subcortical U-fibers ().

Oxycontin Overdose

T1 T1+CT2

CT

T2*

Necrosis of the globus pallidi that is marginated by edema () and postcontrast enhancement (), with additional edema tracking along the left posterior limb internal capsule ().

Pallidal necrosis is a relatively common consequence of overdose related brain injury, particularly in cases that are associated with periods of anoxia.

Delayed Reversible Hypoxic Leukoencephalopathy

T2 FLAIR DWI ADC

History: Spastic quadriparesis and decreased neurologic response, following benzodiazepine overdose complicated by episode of PEA arrest several days before.

Indistinct, symmetric areas of T2 FLAIR hyperintensity are noted within the periatrial white matter and retrolenticular internal capsular regions (), with associated restricted diffusion ().

Delayed reversible hypoxic leukoencephalopathy is a clinical entity that is sometimes encountered in cases of hypoxia/anoxia that is secondary to overdose or other toxic exposure. These patients develop slow-onset clinical deterioration that is associated with signal abnormalities in the deep white matter tracts, although sparing the cortical ribbon. These findings can be near-completely reversible over the course of several weeks to months of rehabilitation.

Benzodiazepine and Hypoxia

T2 T2 FLAIR

DWI ADC CT

Symmetric areas of cytotoxic edema are seen throughout the bilateral globus pallidi (), bifrontal white matter (), periatrial white matter (), splenium, and centrum semiovale ().

History: Found down several days after intentional overdose.

Carbon Monoxide Poisoning

CT T2 FLAIR DWI

case courtesy of Dick Latchaw

History: Hunter found down in shed next to running propane heater

Focal necrosis of the globus pallidi () and demyelination of the bilateral periatrial white matter ().

Carbon monoxide covalently binds to hemoglobiin with an affinity that is several hundred times stronger the oxygen. Saturation of hemoglobin with carbon monoxide therefore leads to severe hypoxic brain injury.

Ethylene Glycol Toxicity

T2 FLAIR

T2 DWI ADC

Extensive cerebral edema is noted throughout the basal ganglia (), thalami (), brainstem (), and temporal lobes ().

History: Auto mechanic found down in garage.

Ethylene glycol is metabolized by alcohol dehydrogenase into glycolic acid, which is subsequently converted to oxalic acid. This leads to an anion gap acidosis that results in cerebral edema and nephrotoxicity.

Alcohol Related Callosal Demyelination

“Marchifava-Bignami disease” is a demyelinating disorder initially described in patients who consumed large quantities of red wine in Italy.

It is associated with chronic alcoholism.

Acute demyelination of the corpus callosum is characteristic of the disease, which may show restricted diffusion

Up to half of the cases occur in combination with Wernicke’s encephalopathy

The treatment is alcohol cessation and supplementation with thiamine and folate.

T2 FLAIR

Focal T2 FLAIR hyperintense lesion centered within the splenium of the corpus callosum (), in this patient with known alcohol abuse.

Marchiafava-Bignami Disease

ADCDWI T2 FLAIR T2

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Top Row: Images demonstrate focal restricted diffusion within the splenium of the corpus callosum (), also known as “the boomerang sign”.Bottom row: Residual T2-shine through is seen throughout the splenium after initation of treatment (), associated with improving neurologic findings.

Another Case of Marchiafava-Bignami

T2 FLAIR

T2 FLAIR T1

DWI ADC

At Presentation

3 weeks laterTop Row: Images demonstrate focal edema within the splenium (), with associated restricted diffusion ().

Bottom row: Interval follow-up demonstrates central cavitation of the lesion (), compatible with necrosis and peripheral gliotic changes

IN SUMMARY

• CNS imaging abnormalities are associated with the toxic and therapeutic effects of both pharmaceutical and non-pharmacologic agents.

• The clinical and imaging features of drug toxicity can share a high degree of overlap.

• In many cases, the imaging and clinical features of CNS drug toxicity may be reversible if recognized early enough.

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