DECREASED MENTAL STATUS AND CENTRAL DEMYELINATING EMERGENCIES

Bradley Osterman

Pediatric neurology – R4

Summer lecture series 2012

PLAN

Introduction

Consciousness & impaired consciousness

Coma

Etiologies of coma

DD of coma-like states

Demyelinating emergencies

ADEM

NMO

Demyelinating w/u of a CIE

INTRODUCTION

Patient brought into the ER unconscious

First reflex

The « ABC »

But don’t forget about the « D » !

Disability

CONSCIOUSNESS

What does it mean to a neurologist?

Product of two basic brain functions (1) Arousal – wakefulness

ARAS (ascending reticular activating system)

(2) Awareness encompasses multiple functions - attention, memory & executive function

Impaired consciousness can result from derangement in :

(1) arousal,

(2) awareness,

(3) or both, in varying degress

IMPAIRED CONSCIOUSNESS

There is a wide spectrum

Avoid confusing, imprecise terms such as : Somnolence, stupor, obtundation, lethargy

Use specific statements to describe the patient’s LOC: Ex. « patient responds to painful sternal rub by grimacing & moving R arm »

GLASCOW COMA SCALE

Has its limitations.

Originally designed for TBI

GCS 12-14 – mild alteration of

consciousness

GCS 9-11 – moderate

GCS 8 and below – severe

COMA

The term « coma » is actually a specific state of consciousness

characterized by : A complete absence of both (1) arousal & (2) awareness

For ≥ 1 hour

Absence of normal sleep-wake cycle

No spontaneous or stimulus-induced eye-opening

No purposeful mvts

Be familiar with the DD of coma-like conditions

ETIOLOGIES OF COMA

(1) Direct insult to the CNS

Structural causes

Supratentorial (ie. Brain tumor, hemorrage, encephalitis)

Subtentorial (ie. Midbrain infarction, acute demyelination of brainstem )

Seizures (NC SE)

Hydrocephalus/raised ICP

Traumatic brain injury (TBI)

(2) Metabolic/toxic causes

DD OF COMA-LIKE CONDITIONS 

Condition Arousal Awareness Motor function Breathing Sleep-Wake

Locked-in syndrome N N

No (exc. eye blinking & vertical

eye mvt) N N

Akinetic mutism N partially present decreased mvts N N

Minimally conscious state N

partially present (minimally)

nonpurposeful (or very limited) N N

Vegetative state N absent nonpurposeful N N

Coma absent absent nonpurposeful N absent

Brain death absent absentNo (exc. spinal

reflexes) absent absent

LOCKED-IN SYNDROME

Occurs with brainstem injuries sparing the midbrain

Patients have normal (1) arousal & mostly intact (2) awareness,

but have a severely limited ability to communicate due to paralysis of voluntary muscles & anarthria

Can be seen with : Pontine glioma

Basilar artery occlusion

Profound neuromuscular dysfunction (GBS, SMA, botulism, organophosphate toxicity)

Trauma

AKINETIC MUTISM

State of profound apathy with partially intact awareness, and paucity and

slowness of voluntary mvts (1) Normal arousal, and (2) mostly intact awareness (normal attentive pursuit)

On the verge of initiating speech or motor activity (but never happens)

Seen with bilateral injuries to the midbrain, basal diencephalon, or inferior

frontal lobes, occuring in : Tumors or tumor resection (mainly posterior fossa)

TBI

Hydrocephalus

CNS infections

MINIMALLY CONSCIOUS STATE

Relatively new term

(1) Arousal present & (2) minimally present awareness

Patients capable of reproducible & purposeful (albeit very limited) motor

movements or affective behaviour Ex. following simple commands,

reaching accurately for an object,

crying or smiling in response to emotional stimuli

VEGETATIVE STATE

Arousal present

Awareness absent (self & environment)

No voluntary or purposeful mvts

Preserved respiratory function & sleep-wake cycles

Including periods of spontaneous eye-opening

Intact brainstem & hypothalamic function

Considered permanent if lasts :

> 12 months after TBI or

> 3 months after non-traumatic brain injury

BRAIN DEATH

Complete & irreversible loss of (1) brain and (2) brainstem

function, characterized by :

Loss of consciousness

Loss of cranial nerve function

Loss of motor function

Loss of breathing activity

Loss of sleep-wake cycle

Specific criteria – complete brain death exam

DD OF COMA-LIKE CONDITIONS 

Condition Arousal Awareness Motor function Breathing Sleep-Wake

Locked-in syndrome N N

No (exc. eye blinking & vertical

eye mvt) N N

Akinetic mutism N partially present decreased mvts N N

Minimally conscious state N partially present

nonpurposeful (or very limited) N N

Vegetative state N absent nonpurposeful N N

Coma absent absent nonpurposeful N absent

Brain death absent absentNo (exc. spinal

reflexes) absent absent

DEMYELINATING EMERGENCIES 

ADEM (ACUTE DISSEMINATED ENCEPHALOMYELITIS)

An autoimmune-mediated inflammatory episode involving the CNS Usually monophasic (5-20% cases are multi-phasic)

Usually following an infection (or vaccination; 3-6% of cases) Up to 4 weeks prior to sx (gen. 1-20 days)

Children > adults (peak ages 5-8 y/o) Incidence 8/1,000,000; seasonal increase in spring & winter months

Described equally in all racial, ethnic groups and genders (unlike MS)

Mortality rate – 5% Full recovery – 50-75%

Average time to recovery – 6 months

ADEM – CLINICAL PRESENTATION

Abrupt onset

With rapid progression – maximum deficits < 1 week (average 4.5 days)

Encephalopathy

Mild to severe alteration in mental status (irritability to coma)

Convulsive seizures (25%)

Focal neuro aN

Weakness, ataxia, visual aN, sensory aN, cranial nerve aN, sphincter dysfunstion

Constitutional sx

H/A, No/Vo, malaise

ADEM – PHYSICAL EXAM

Alteration in mental status (>90%)

Cranial nerve aN (35-50%) (w/ possible brainstem dysfunction)

Meningeal signs (20%)

Weakness (50-75%)

Hemiparesis, diaparetic, generalized

Long tract signs (80%)

Clonus, increased DTR, upgoing toes

Ataxia (35-60%)

Sensory deficits (15-20%) (w/ possible sensory level)

ADEM – MRI

ADEM – axial T2-weighted images

Large, T2-hyperintense, patchy, poorly circumscribed

ADEM – MRI

ADEM – sagittal cervical spine & axial T2-weighted brain images

Large, T2-hyperintense, patchy, poorly circumscribed

ADEM – MRI

Typically involves the gray-white junction

ADC map – consistent w/ vasogenic edema

Gado-enhancing (30-90%)

Compared to MS

Periventricular lesions (30-45%) and corpus callosum

lesions (20-25%) are less common in ADEM

Additional lesions found in:

optic nerves, basal ganglia (30-40%), the thalamus (30-

40%), the brainstem (45-55%), the cerebellum (30-40%) &

spinal cord

ADEM – INVESTIGATIONS

Lumbar puncture

leukocytosis (80%); N/elevated OP, protein often > 1.0; N glucose; absent OCB

CSF cultures, serologies typically negative

EEG – diffuse slowing

Work-up for other Demyelinating disorders & Mimics

ADEM – TREATMENT

1st line tx – high-dose IV corticosteroids

Methylprednisolone (Solumedrol) – 30 mg/kg/day x 5 days

Up to max 1 G Solumedrol daily x 5 days (ie. Like in adults)

Followed by 3-6 weeks of tapering prednisone

Less than 3 week taper has a higher risk of relapse

2nd line – IVIG

and/or plasma exchangev(PLEX)

ADEM – EVOLUTION/CLASSIFICATION Monophasic (same acute episode)

With fluctuating/subsequent sx as long as the relapse is : < 3 months of onset < 1 month following steroid tx

Recurrent ADEM Relapse with identical sx ≥ 3 months or ≥ 1 month following steroid tx

Multi-Phasic Relapse with new features and change in mental status ≥ 3 months or ≥ 1 month of steroid tx MRI must show new areas of involvement & partial resolution of previous lesions

ADEM – FLOWCHART

NMO – NEUROMYELITIS OPTICA

NMO or Devic’s disease

Idiopathic, inflammatory, necrotizing demyelination of the CNS

Simultaneous or successive involvement of :

optic nerves & spinal cord

Mediated by anti-NMO-IgG antibodies

Unlike MS, not T-cell mediated

Targets the protein aquaporin 4 in the cell membrane of astrocytes

Impaired water transport across the membrane leading to inflammatory demyelination

NMO – CLINICAL PRESENTATION

Visual loss (painful & subacute)

Optic neuritis (ON)

Spinal cord dysfunction

Transverse myelitis (TM)

weakness

sensory deficits (w/ level)

sphincter dysfunction

Unilateral ON (45%); simultaneous & bilateral ON (25-30%)

Isolated TM (10-15%)

Simultaneous ON & TM (10-15%)

NMO – DIAGNOSTIC CRITERIA

NMO – TREATMENT

High-dose glucocorticod therapy

IVIG/PLEX

Obtain sample for anti-NMO ab prior

Immunosuppressant therapy

Ex. Imuran

NMO – PROGNOSIS

High rate of recurrence (> 90%)

Relapse within first year (50%), and within 5 years (90%)

Relapse interval generally < 3 months

Deficits (ON/TM) tend to be severe & recovery incomplete

Permanent leg paralysis and/or blindness in > 50%

DEMYELINATING (CIS) WORK-UP – AT MCH

Serum

CBC, Glucose, Lactate, TSH, T4, vit B12, IgG index, VLCFA

ESR, CRP, ANA, dsDNA, APLA, ACE (vasculitic w/u)

Viral serologies (HIV, VDRL, HSV)

Lyme (serology +/- PCR)

CSF

Cell count (WBC), Glucose, Protein, Lactate (on ice)

OCB (w/ serum IgG index)

Viral culture (enterovirus, CMV), Bacterial culture

Herpes PCR, Mycoplasma PCR

QUESTIONS?