MULTIPLE SCLEROSIS AND ALLIED

DEMYELINATIVE DISEASES
Dr. Oronce
Neurology

DEMYELINATIVE DISEASES
PATHOLOGIC CRITERIA:
Destruction of the myelin sheaths of
nerve fibers
Relative sparing of the other elements
of nervous tissue, i.e., of axis
cylinders, nerve cells, and supporting
structures
Infiltration of inflammatory cells in a
periventricular distribution
Particular distribution of lesions, often
perivenous and primarily in white
matter, either in multiple small
disseminated foci or in larger foci
spreading from one or more centers
Relative lack of wallerian
degeneration or secondary
degeneration of fiber tracts
CLASSIFICATION:
I. Multiple sclerosis (disseminated
sclerosis)
o Chronic relapsing encephalomyelitis
o Acute multiple sclerosis
o Diffuse sclerosis of Schilder and
concentric sclerosis of Balo
II. Neuromyelitis optica (Devic)
III. Acute disseminated
encephalomyelitis
o Post-infectious: chickenpox,
smallpox, mumps, rubella, influenza;
viral and bacterial infections
o Post-vaccinal: rabies or smallpox
IV. Acute and subacute necrotizing
hemorrhagic encephalitis
o Acute hemorrhagic
leukoencephalopathy
o Subacute necrotic myelopathy
MULTIPLE SCLEROSIS
Among the most venerable of
neurologic diseases and one of the
most important by virtue of its
frequency, chronicity and tendency
to attack young adults
Episodes of focal disorder of the
optic nerves, spinal cord and brain
which remit to a varying extent

and recur over a period of many

years
Classic features: motor weakness,
paraparesis, paresthesias,
impaired vision, diplopia,
nystagmus, intention tremor,
ataxia, impairment of deep
sensation, and bladder dysfunction
Long period of latency (1 to 10
years) between a minor initial
symptom
In most cases, the initial
manifestations improve partially or
completely, to be followed after a
variable interval by the recurrence
of the same abnormalities or the
appearance of new ones in other
parts of the nervous system
In as many as 50% of patients,
intermittently progressive or
sometimes, steadily progressive
Diagnosis of MS is not secure
unless there is a history of
remission and relapse and
evidence on examination of more
than one discrete lesion of the CNS

PATHOLOGIC FINDINGS:
Lesions (plaques) affect principally
the white matter of the brain and
spinal cord and do not extend
beyond the root zones of the
cranial and spinal nerves
Periventricular location: adjacent
to the bodies and atria of the
lateral ventricles
Other favored sites: optic nerves
and chiasm, spinal cord
Lesions destroy myelin sheaths but
leave the nerve cells essentially
intact
Recent lesions show a partial or
complete destruction and loss of
myelin
Variable but slight degeneration of
oligodendroglia, a neuroglial
(astrocytic) reaction, and
perivascular and para-adventitial
infiltration with mononuclear cells
and lymphocytes
Macrophages infiltrate the lesions,
and astrocytes in and around the
lesions increase in number and
size
Page 1 of 10

Long-standing lesions are

composed of thickly matted,
relatively acellular fibroglial tissue,
with only occasional perivascular
lymphocytes and macrophages
In old lesions with interruption of
axons, there may be descending
and ascending degeneration of
long fiber tracts in the spinal cord
Exceptionally, a few of the older
lesions undergo cavitation,
indicating that not only myelin and
axons have been affected but also
supporting tissues and blood
vessels as well

ETIOLOGY AND EPIDEMIOLOGY:

15% of MS patients have an
affected relative, with the highest
risk of concurrence (5%) observed
in the patients siblings
34% (monozygotic twins); 4%
(dizygotic twins)
Certain histocompatibility antigens
(HLAs) more frequent in patients
with MS: DR locus on the 6th
chromosome, HLA-DR2,-DR3,-B7,A3 (markers for an MS
susceptibility gene)
Two to three times higher in
women; incidence in children: 0.3
to 0.4%; age of onset between 2040 years old
Greater among rural than urban
dwellers, in the higher
socioeconomic groups
PATHOGENESIS:
1. Viral Infection
Alterations in humoral and cellmediated immunity to viral agents
though no virus has been isolated
from tissues of patients with MS
Chlamydia pneumoniae and herpes
virus 6 have been implicated but
their participation in the disease is
no more compelling than that for
any other infectious agent
Some secondary factor after the
viral or other infection must be
operative
This secondary mechanism is an
autoimmune reaction, attacking
some components of myelin and

destroying tissue elements,

including axons
Different viruses (rubeola, rubella
and varicella) could cause
autoimmunization of Tlymphocytes against myelin basic
protein (MBP)
This means that the T-lymphocyte
recognizes an identical structure in
the virus and myelin sheath
Molecular mimicry (a shared
antigen between the virus and CNS
myelin or the oligodendrocyte) has
been invoked as a mechanism
2. Humoral Factors
The presence in the CSF of
oligoclonal immune proteins, which
are produced by B-lymphocytes
within the CNS
Damage the myelin, inhibit
remyelination and block axonal
conduction
Antibodies to oligodendrocytes are
present in the serum of up to 90%
in patients
3. Cellular Factors
T-lymphocytes which regulate
humoral immune responses are
found in abundance within MS
plaques
They are either potentiators (Thelper cells) or inhibitors (Tsuppressor cells) of
immunoglobulin production by the
B-lymphocytes
T-cell receptors respond to
antigens presented by major
histocompatibility complex, or MHC
class II molecules and
macrophages and astrocytes
Such interaction is thought to
stimulate T-cell proliferation and
the secretion of cytokines
Breakdown of the blood-brain
barrier, destruction of
oligodendrocytes and myelin
A reduction in T-cells, both helper
and suppressor subsets, or an
increase in helper-suppressor
rations, appears to be associated
with increasing disability in
patients with MS

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MS as a T-cell-mediated disease is
supported by evidence that T-cells
initiate the lesions of experimental
allergic encephalomyelitis
Intense T-cell stimulation is in itself
sufficient to induce demyelination
Still, the immune mechanisms that
are operative in the genesis of MS
cannot as yet be specified

PHYSIOLOGIC EFFECTS OF
DEMYELINATION
Impedes saltatory electrical
conduction from one node of
Ranvier, where sodium channels
are concentrated, to the next node
Resulting failure of electrical
transmission underlies most of the
abnormalities of function from
demyelinating disease of both
central and peripheral nerve fibers
Extreme sensitivity of conduction
in demyelinated nerve fibers to
elevated temperature (temporary
reduction of symptoms by heat or
exercise)
Hyperventilation slows conduction
of the visual evoked potential;
smoking, fatigue are all capable of
briefly worsening neurologic
functioning and are easily confused
with relapses of MS

PRECIPITATING FACTORS:
Most common are infection,
trauma and pregnancy; however,
none has been convincingly related
to an increased risk of new attacks
of MS
Respiratory or gastrointestinal viral
infections that precede the onset
of exacerbations of MS varies from
5-50%
Endogenous infections (labial or
genital herpes) have regularly
preceded an attack of MS
No significant correlation between
traumatic episodes and
exacerbation of MS
CLINICAL MANIFESTATIONS:
Fatigue, lack of energy, weight loss
and vague muscle and joint pains
before the onset of neurologic
symptoms

20%: neurologic symptoms fully

developed in a matter of hours
30%: symptoms evolve more
slowly (a day or more); another
30%: weeks to months; 10%:
insidious onset and slow, steady or
intermittent progression over
months and years
Relapsing-remitting pattern
appears in patients less than 40
years old
Early Symptoms and Signs:
o Weakness or numbness is the
initial symptom in 50%
o Tingling of the extremities,
tight band-like sensations
around the trunk or limbs
commonly associated
o Dragging or poor control of one
or both legs; spastic or ataxic
paraparesis
o Tendon reflexes become
hyperactive; abdominal
reflexes disappear
o Variable degrees of deep and
superficial sensory loss
o Symptoms in one leg but with
signs in both: adage in patients
with MS
o Weakness, incoordination, or
numbness or tingling in one leg
but with bilateral Babinski
signs
o Lhermitte sign: tingling,
electric-like feeling down the
shoulders, back and anterior
thighs on passive flexion of the
neck (increased sensitivity of
demyelinated axons to the
stretch or pressure on the
spinal cord)
o Dull, aching low back pain;
sharp burning, poorly localized,
or lancinating-radicular pain in
a limb or trunk
o Cerebellar ataxia and
brainstem symptoms (vertigo,
facial pain, numbness,
dysarthria, diplopia, disorders
of micturition)
Optic Neuritis:
o Initial manifestation in about
25% of all MS patients
o Partial or total loss of vision in
one eye; pain within the orbit,
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worsened by eye movement or

palpation of the globe
o Scotoma involving the macular
area and blind spot
(cecocentral) or other field
defects
o Evidence of swelling or edema
of the optic nerve head
(papillitis) in about half the
patients
o Papillitis:severe and acute
visual loss
o About 2/3 of patients with optic
neuritis recover completely;
improvement begins within 2
weeks of onset, perhaps sooner
with corticosteroid treatment
o 50% or more of adult patients
with optic neuritis will
eventually develop other signs
of MS (74% in women, 34% in
men by the 15th year after the
optic neuritis)
o Most do so within 5 years of
the original attack
o Uveitis and sheathing of the
retinal veins are other
disorders that have a higher
than expected incidence in
patients with MS
Acute Myelitis (Transverse
Myelitis)
o In MS, the spinal cord signs are
asymmetrical and incomplete
and involve only the long
ascending and descending
tracts
o Rapidly evolving paraparesis,
symmetrical or asymmetrical
paraparesis, a sensory level on
the trunk, sphincteric
dysfunction, and bilateral
Babinski signs
o 1/3 of patients report an
infectious illness in the weeks
preceding the onset of
neurologic symptoms
(monophasic postinfectious
demyelinating disease)
Other Patterns of MS:
o Unsteadiness in walking,
brainstem symptoms (diplopia,
vertigo, vomiting), paresthesias
or numbness of an arm or leg,

facial pain, disorders of

micturition
o Slowly progressive cervical
myelopathy with weakness and
ataxia: in elderly women
o Nystagmus and ataxia with or
without weakness and
spasticity of the limbs
o Cerebellar ataxia: scanning
speech, rhythmic instability of
the head and trunk, intention
tremor of the arms and legs,
incoordination of voluntary
movements and gait
o Charcots triad: nystagmus,
scanning speech, intention
tremors
o Diplopia: internuclear
ophthalmoplegia (involves the
medial longitudinal fasciculus);
paresis of the medial rectus on
attempted lateral gaze with a
coarse nystagmus in the
abducting eye
o Bilateral internuclear
ophthalmoplegia in a young
adult virtually diagnostic of MS
o Myokymia or paralysis of facial
mucles, deafness, tinnitus
o Transient facial hypesthesia or
anesthesia or of trigeminal
neuralgia in a young adult
should suggest the diagnosis of
MS
Established Stage of the
Disease:
o 50%: mixed or generalized
type (involves optic nerves,
brainstem, cerebellum, and
spinal cord)
o 30 to 40%: spinal form (spastic
ataxia and deep sensory
changes in the extremities)
o 5%: cerebellar or
pontocerebellar form
o Symptoms of bladder
dysfunction (hesitancy,
urgency, frequency and
incontinence) occur commonly
with spinal cord involvement;
in males, often associated with
impotence
o Abrupt attacks of neurologic
deficits (few seconds or
Page 4 of 10

o
o

o
o

minutes) many times daily are

well-recognized features of MS
The attacks occur during the
relapsing and remitting phase
of the illness
Consists of dysarthria and
ataxia, paroxysmal pain,
dysesthesia in a limb, flashing
lights, paroxysmal itching or
tonic seizures
Attributed to ephaptic
transmission (cross-talk)
between adjacent
demyelinated axons within a
lesion
Severe fatigue, often transient,
is more likely to occur in febrile
states or with evidence of
disease activity
Typical tic douloureux in young
patients; bibrachial, thoracic or
lumbosacral pain (thermal and
algesic dysesthesias)
3% have focal seizures; coma
during relapse
Confusional psychosis with
drowsiness; slow intellectual
decline with slight cerebellar
ataxia
Rapid onset of ascending
paralysis of legs, bladder and
bowel and trunk with severe
pain in sacral parts and
areflexia

VARIANTS OF MS:
1. Acute Multiple Sclerosis:
o Combination of cerebral,
brainstem, and spinal
manifestations
o Few weeks: stupor, coma, or
decerebrate posturing with
prominent cranial nerve and
corticospinal abnormalities
o Has typical of the acute
plaques of MS, however,
many plaques are of the same
age and the confluence of
many perivenous
demyelination is more
obvious
o Main consideration in
differential diagnosis is a CNS
vasculitis
2. Neuromyeltis Optica

Devic Disease; Necrotic

Myelopathy
o Simultaneous or successive
involvement of optic nerves
and spinal cord
o An acute to subacute onset of
blindness in one or both eyes,
preceded or followed by a
transverse or ascending
myelitis
o Spinal cord lesions often
necrotizing rather than purely
demyelinative
o Stands apart from MS: failure
to develop brainstem,
cerebellum or cerebral
demyelinative lesions and
normal MRI of the cerebral
white matter
o Stands apart from MS: almost
uniform absence of
oligoclonal bands and other
abnormalities of IgG in the
spinal fluid; necrotizing and
cavitary nature of the spinal
cord lesion, affecting white
and gray matter alike, with
prominent thickening of
vessels but without
inflammatory infiltrates
o Differential diagnosis:
arteriovenous malformation
and infarction of the cord
o Treatment has been largely
unsuccessful despite
aggressive therapy with
corticosteroids and
cyclophosphamide
3. Diffuse Cerebral Sclerosis of
Schilder
o Schilder Disease; Encephalitis
Periaxialis Diffusa
o Cerebrum is the site of
massive demyelination
occurring in multiple foci or as
a single large focus
o More frequent in childhood
and adolescence
o Case report of a 14-year-old
girl with progressive mental
deterioration and signs of
increased intracranial
pressure, that terminated
fatally in 19 weeks
o

Page 5 of 10

Nonfamilial; runs a
progressive course. either
steady and unremitting or
punctuated by a series of
episodes of rapid worsening
o Dementia, homonymous
hemianopia, cerebral
blindness and deafness,
varying degrees of
hemiplegia, and pseudobulbar
palsy
o CSF without oligoclonal
bands; instead, large
quantities of myelin basic
protein in the CSF
o Large, sharply outlined,
asymmetrical focus of myelin
destruction often involving an
entire lobe or cerebral
hemisphere
o Concentric sclerosis of Balo:
variant of Schilder disease;
resembles in its clinical
aspects and the overall
distribution of lesions
4. Concentric Sclerosis of Balo:
o Distinguishing feature:
alternating bands of
destruction and preservation
of myelin in a series of
concentric rings
5. MS in Conjunction with
Peripheral Neuropathy
o Polyneuropathy or
mononeuropathy multiplex
o An autoimmune
demyelination incited in both
spinal cord and peripheral
nerve
o Takes the form of a chronic
inflammatory
paolyradiculoneuropathy
(CIDP)
o

LABORATORY FINDINGS:
1. Cerebrospinal Fluid:
o With acute onset or
exacerbation, moderate
mononuclear pleocytosis
o Increased CSF protein
o Increased CSF gamma
globulin (IgG): > 12% of the
total protein
o Presence of oligoclonal bands
(abnormal discrete

populations of gamma
globulin)
o Presence of oligoclonal bands
in a first attack of MS is
predictive of chronic relapsing
MS
o Myelin Basic Protein (MBP):
increased during acute
exacerbations of MS, normal
in slowly progressive MS and
during remissions
2. MRI in MS:
o Most helpful ancillary
examination in the diagnosis
of MS (ability to reveal
asymptomatic plaques in
cerebrum, brainstem, optic
nerves, and spinal cord)
o MS plaques are hypointense
(white) on T2-weighted
images and more strikingly
obvious on FLAIR images
o T2 weighted image: several
asymmetrical, welldemarcated lesions
immediately adjacent to the
ventricular surface
o Diagnostic: oval or linear
regions of demyelination,
oriented perpendicular to
the ventricular surface and
corresponding to the radially
oriented fiber bundles of the
white matter and
periventricular veins

3. Evoked Potentials and Other

Tests:
Page 6 of 10

o
o
o

Abnormal visual evoked

responses in 70% of patients
with the clinical features of
definite MS and in 60% with
probable or possible MS
Somatosensory evoked
responses: 69% (definite MS);
51% (probable or possible MS)
Brainstem auditory evoked
responses: 47% (definite MS);
20% (possible or probable MS)
CT scan may also
demonstrate cerebral lesions;
acute plaques may simulate
abscess or tumor and some
contrast-enhanced
periventricular lesions
become radiologically
inevident after steroid
treatment

CLINICAL COURSE AND PROGNOSIS:

Some patients will have a complete
clinical remission after the initial
attack, or rarely, a series of
exacerbations each with complete
remission
Relapse rate: 0.3 to 0.4
attacks/year; interval between the
opening symptom and the first
relapse is highly variable: 1, 2, 5-9,
10-30 years
After a number of years, there is an
increasing tendency for the patient
to enter a phase of slow, steady or
fluctuating deterioration of
neurologic function
In about 10% of cases, the clinical
course is almost evenly progressive
from the beginning.
Pregnancy does not have an
adverse effect on MS; typically
associated with clinical stability or
even with improvement
There appears to be an increased
risk of exacerbation in the first few
months postpartum
Duration of the disease varies; may
survive up to 25 years (average
duration of the disease is in excess
of 30 years)
TREATMENT:
Corticosteroids:

On the basis of clinical trials, only

adrenocorticotropic hormone
(ACTH), methylprednisolone,
prednisone, cyclophosphamide and
beta-interferon have proved to have
a beneficial effect on the disease
and on MRI lesions
IV administration of massive doses
of methyprednisolone: bolus of 5001000 mg/day for 3-5 days
Then, prednisone 60-80 mg/day,
tapering the dosage over a 12-day
period: generally effective in
aborting or shortening an acute or
subacute exacerbation of MS or of
optic neuritis
If impractical to use parenteral
methylprednisolone, may substitute
oral: 48 mg/day for 1 week, followed
by 24 mg/day for 1 week, then, 12
mg/day for 1 week
Alternate-day steroid treatment
offers little benefit
Pulses of high-dose intravenous
steroids administered once each
month seem to keep some patients
from having relapses and are better
tolerated than the continuous
administration of oral medications

TREATMENT OF OPTIC NEURITIS

Intravenous methylprednisolone
followed by oral prednisone speeds
the recovery from visual loss
Although at 6 months interval,
there is little difference between
patients treated in this way and
those treated with placebo
Methylprednisolone 500 mg orally
for 5 days has beneficial effect on
visual functions at 1 and 3 weeks;
at 8 weeks, no effect could be
shown
Interferon Beta and Copolymer 1:
For relapsing-remitting MS
Interferon beta-1b (Betaseron):
subcutaneous injection every
second day for up to 5 years;
decreases the frequency and
severity of relapses and the
number of new or enlarging MRI
lesions
Treatment with interferon beta-1a
(Avonex) equally effective: 6.6
Page 7 of 10

million units, intramuscular, once a

week
Copolymer 1 (mimics the action of
MBP): 20 mg/day, subcutaneous
Side effects: flu-like symptoms,
sweating and malaise

Immunosuppressive Drugs:
Agents that modify immune
reactivity with limited success
Azathioprine, cyclophosphamide,
total lymphoid irradiation seem to
have improved the clinical course
Burdensome and potentially
serious toxicity risk of neoplastic
change
Other Therapies:
No valid studies for the value of
synthetic polypeptides, hyperbaric
oxygen, low-fat and gluten-free
diets, linoleate supplementation of
the diet
Plasma exchange and
immunoglobulin in fulminant
cases: monthly infusions of IVIG
(0.2 g/kg) for 2 years
General Measures:
Adequate bed rest, prevention of
excessive fatigue and infection,
rehabilitative measures to
postpone the bedridden stage
Fatigue during acute attacks:
Amantadine 100 mg morning and
noon; pemoline 20-75 mg
In urinary retention: bethanecol
chloride; intermittent
catheterization
Urinary urgency and frequency
(spastic bladder): propantheline or
oxybutynin may relax the detrusor
muscle
Constipation: laxatives, properly
spaced enemas
With spastic paralysis and painful
flexor spasms of the legs:
intrathecal infusion of baclofen
Selective injection of botulinum
toxin into the most hypertonic
muscles
For severe and disabling tremor:
isoniazid 300 to 1200 mg/day plus

pyridoxine 100 mg/day;

carbamazepine, clonazepam
Enlist the support of physical and
occupational therapists, visiting
nurses and social workers

ACUTE DISSEMINATED
ENCEPHALOMYELITIS (ADEM)
Postinfectious, Postexanthem,
Postvaccinal Encephalomyelitis
Represents an acute demyelinative
disease, distinguished
pathologically by numerous foci of
demyelination scattered
throughout the brain and spinal
cord
Perivenular inflammatory reaction;
perivascular spaces are infiltrated
with lymphocytes and
mononuclear cells
Adjacent regions of white matter
are invaded by polymorphic
microglia corresponding to the
zones of demyelination
A few days of onset of the
exanthem of measles, rubella,
smallpox and chickenpox; rarely
occurs after influenza and mumps
At present, ADEM appears to
develop after infections with
Epstein-Barr, cytomegalovirus, and
Mycoplasma pneumoniae
Grave: significant rate of
neurologic defects in patients who
survive
In children, recovery from the
acute stage is followed by a
permanent disorder of behavior,
mental retardation or epilepsy
Cerebellitis and ataxia that follow
chickenpox and other infections
are more benign and normally
clear over several months
PATHOGENESIS:
The disorder represents an
immune-mediated complication of
infection rather than a direct
infection of the CNS
An experimental allergic
encephalomyelitis has been
produced by inoculating animals
with sterile brain tissue and
adjuvants: perivenular
demyelinative and inflammatory
Page 8 of 10

lesions that one observes in the

human disease
Presumably, the lesions are the
result of T-cell-mediated immune
reaction to components of myelin
or oligodendrocytes

CLINICAL FEATURES:
Abrupt onset of confusion,
somnolence, and often convulsions
with headache, fever and varying
degrees of neck stiffness
Ataxia, myoclonic movements and
choreoathetosis less frequent
In the more severe cases, stupor,
coma and decerebrate rigidity
occur in rapid succession
In the myelitic form (postinfectious
myelitis): partial or complete
paraplegia or quadriplegia,
diminution or loss of tendon
reflexes, sensory impairment and
varying degrees of paralysis of
bladder and bowel
In postexanthem
encephalomyelitis (2-4 days after
the rash): convulsions, stupor, and
sometimes, coma
Less commonly, hemiplegia or a
virtually pure cerebellar syndrome
and occasionally, a transverse
myelitis, sphincteric disturbance
In less severe cases of
postexanthem encephalitis:
headaches, confusion and signs of
meningeal irritation
CSF: increase in lymphocytes and
protein; MRI shows bilateral
confluent white matter lesions in
both cerebral hemispheres and in
the subcortical white matter as
well

DIFFERENTIAL DIAGNOSIS/
TREATMENT:
Viral meningoencephalitis
Infectious mononucleosis
Herpes simplex
Mycoplasmal infections
Cerebrovascular disease
(thrombophlebitis)
Hypoxic encephalopathy
Acute toxic hepatoencephalopathy
(Reye syndrome)
High-potency steroids the best
choice of treatment
Plasma exchange and IV
immunoglobulin successful in some
fulminant cases
POSTVACCINAL
ENCEPHALOMYELITIS:
Complicates the injection of old
rabies vaccine
Evolution of symptoms: subacute
(2-4 weeks), demyelinative lesions
are macroscopic, composed of
confluent perivenous lesions
Encephalomyelitis following
vaccination against smallpox has
now disappeared
Combination of encephalitic and
myelitic features; may involve
nerve roots and peripheral nerves
Mortality rate: 30-50%; residual
neurologic signs, intellectual
impairment, behavioral
abnormalities
ACUTE NECROTIZING HEMORRHAGIC
ENCEPHALOMYELITIS
Acute Hemorrhagic
Leukoencephalitis of Weston Hurst
Page 9 of 10

Most fulminant form of

demyelinative disease; mainly in
young adults and children
Almost invariably preceded by a
respiratory infection (Mycoplasma
pneumoniae)
Headache, fever, stiff neck and
confusion; followed by focal
seizures, hemiplegia or
quadriplegia, pseudobulbar
paralysis and progressively
deepening coma
CSF under increased pressure;
lymphocytes to a
polymorphonuclear pleocytosis of
up to 3000 cells/cu mm; increased
protein, normal sugar
Most fulminant form of
demyelinative disease; mainly in
young adults and children
Almost invariably preceded by a
respiratory infection (Mycoplasma
pneumoniae)
Headache, fever, stiff neck and
confusion; followed by focal
seizures, hemiplegia or
quadriplegia, pseudobulbar
paralysis and progressively
deepening coma
CSF under increased pressure;
lymphocytes to a
polymorphonuclear pleocytosis of
up to 3000 cells/cu mm; increased
protein, normal sugar
CT scan and MRI: bilateral but
asymmetrical large, confluent
edematous lesions in the cerebral
white matter

Terminates fatally in 2-4 days

Differential diagnosis: brain
abscess, subdural empyema, local
embolic encephalomalacia, herpes
simplex virus encephalitis
Pathologic features:
white matter of one or both
hemispheres destroyed almost to
the point of liquefaction
tissue flecked with multiple small
hemorrhages
changes also found in the
brainstem, cerebellar peduncles,
spinal cord
Histologic examination:
widespread necrosis of small blood
vessels and brain tissue around the
vessels; intense cellular infiltration,
multiple small hemorrhages and an
inflammatory reaction in the
meninges
Histologic features similar to ADEM
but with more widespread necrosis
and tendency of lesions to form
large foci
Etiology: lymphocytes undergo
transformation to lymphoblasts in
response to a pure
encephalitogenic MBP
Delayed hypersensitivity
mechanisms are operative
Treatment: corticosteroids,
plasma exchange, IV
immunoglobulin
__END__

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