Download MULTIPLE SCLEROSIS (MS)

Essentials of Clinical Neurology: Demyelinating Disease
LA Weisberg, C Garcia, R Strub
www.psychneuro.tulane.edu/neurolect/
21-1
CHAPTER 21
Demyelinating Disease
Demyelinating diseases are disorders of unknown cause characterized by focal breakdown of
previously normal central nervous system (CNS) myelin with relative preservation of axons. By
this definition, hypoxia, leukodystrophies, toxic-metabolic conditions—such as subacute
combined degeneration and central pontine myelinolysis—and other secondary lesions of CNS
myelin are excluded.
MULTIPLE SCLEROSIS (MS)
MS is characterized by disseminated multifocal deterioration of CNS myelin. It is a chronic
inflammatory demyelinating immune mediated (autoimmune) CNS disease.
There is
inflammatory demyelination, axonal loss and brain atrophy. The clinical presentation consists of
impairment of motor, sensory, cerebellar, visual function; however, MS may begin as clinically
isolated syndromes (CIS) including optic neuritis, transverse myelitis, brain stem disorder with
bilateral internuclear ophthalmoplegia and nystagmus, tremor, dysarthria with scanning speech,
ataxia. Fifty to 80% of patients with CIS show MRI evidence of occult demyelinating lesions
utilizing MRI. Fifty percent of patients with relapsing-remitting form develop secondary
progressive form in 10 years and 90% develop secondary progressive form in 25 years. MS
usually starts in early adulthood and is "the great crippler of young adults." It is the major cause
of disability in young patients. When physicians who initially evaluate patients with
neurological symptoms, including MS patients - e.g., ophthalmologists, primary care physicians,
emergency physicians, obstetricians-gynecologists - their image is that of a young woman in a
wheelchair; however, there is a much wider spectrum and many patients are fully functional,
leading active lives at home and in work-place. You would never recognize that these patients
have MS!
MS can have a varied course including relapsing-remitting course, relapsing-remitting
onset with secondary progressive neurologic impairment, primary progressive deterioration;
alternatively some patients may have no symptoms and diagnosis is established by MRI or
autopsy . The clinical manifestations vary from patient to patient and from attack to attack
without a predetermined pattern; however, initial symptoms recur more commonly than new
symptoms developing. Motor deficit in one or more extremities occurs in 50% of patients; it is
either isolated or associated with the sensation of numbness or tingling in one extremity or a
band-like numbness or pressure around the trunk. In 25% of patients the initial symptom is
monocular blindness as a result of retrobulbar neuritis or papillitis. Other symptoms include
unsteadiness of gait as a result of cerebellum or cerebellar tract lesions and brain stem deficits,
including impaired ocular motility (internuclear ophthalmoplegia, horizontal or vertical nystagmus), vertigo, or crossed sensorimotor findings. A tingling or electric shock-like feeling that
radiates down the back or thighs and is triggered by passive neck flexion (Lhermitte's sign) can
be seen in patients who have spinal cord lesions. The lower extremities are affected earlier and
more frequently than the upper extremities and consist of spasticity, flexor spasms, and
Essentials of Clinical Neurology: Demyelinating Disease
LA Weisberg, C Garcia, R Strub
www.psychneuro.tulane.edu/neurolect/
21-2
hyperreflexia. Two thirds of the patients show disturbance of sphincter control. Seizures can
occur rarely because this disorder does not extend to the cerebral cortex.
The recommended diagnostic criteria for MS used to include the terms "clinically
definite" and "clinically probable" (see Box 21-1). The Internal Panel on MS revised these
criteria to include the following (1) evidence of dissemination in time and space of typical MS
lesions; (2) objective clinical signs typical of MS on examination; (3) MRI, CSF and evoked
potential abnormalities consistent with MS. MRI is most sensitive sign and CSF shows evidence
of immunological and inflammatory disorder and is most specific sign of MS. Based upon these
features, the patient is classified as having MS or not having MS.
Cognitive impairment and behavioral disorders occur and are manifested by euphoria,
denial of illness, or depression and may occur in the early stages. Patients complain that their
thinking process is slowed. Fatigue is a complaint in most patients with MS and this may be
physical or mental type, and is due to demyelination and electrical conduction failure. It is
perhaps the most disabling feature of MS. Assessing neurologic impairment is also difficult but
was standardized by the Kurtzke Expanded Disability Status Scale.
BOX 21-1
Clinically definite MS (CDMS)
Two attacks and clinical evidence of two separate lesions
Two attacks; clinical evidence of one lesion and paraclinical evidence of another, separate lesion
Laboratory-supported definite MS (LSDMS)
Two attacks; either clinical or paraclinical evidence of one lesion; and CSF oligoclonal bands
(OB) or increased CNS synthesis of IgG
One attack; clinical evidence of two separate lesions; and CSF OB/IgG
One attack; clinical evidence of one lesion and paraclinical evidence of another, separate lesion;
and CSF OB/IgG
Clinically probable MS (CPMS)
Two attacks and clinical evidence of one lesion
One attack and clinical evidence of two separate lesions
One attack; clinical evidence of one lesion and paraclinical evidence of another, separate lesion
Laboratory-supported probable MS (LSPMS)
Two attacks and CSF OB/IgG
Essentials of Clinical Neurology: Demyelinating Disease
LA Weisberg, C Garcia, R Strub
www.psychneuro.tulane.edu/neurolect/
21-3
Etiology
MS is an immune-mediated (autoimmune) disease. In certain genetically susceptive individuals,
there is a heightened immunological response. When this individual is infected by certain
common and widespread bacteria or viruses, the exuberant immunological response to these
foreign invaders does not allow a distinction of "non-self" (virus, bacteria) from "self" (myelin)
and the inflammatory demyelination in CNS occurs. The inability to distinguish "self" from
"non-self" is called "molecular mimicry". This immunological boosting response may cause
multiple relapses. Environmental factors may explain why the disease is more prevalent in
temperate than in tropical areas. High risk persists if migration from high-risk areas to low-risk
areas occurs after the fifteenth birthday, implying that risk factors have their effect during
childhood. About 10% of patients with MS have an affected relative. The concordance rate in
monozygotic twins is 20% to 40% and in dizygotic twins 15%. Genetic factors are related to the
human lymphocyte antigen (HLA) complex, primarily HLA-A3 and B7. There are genetically
susceptible individuals in whom the enhanced immunological response occurs with certain
environmental exposures. Precipitating factors for relapses may be nonspecific triggers trauma, lumbar puncture, pregnancy, multiple types of infection.
Elevation of antibodies against measles, rubella, mumps, and herpes viruses has been
found in the serum and CSF of some MS patients; however, the significance of these findings
has not been established. Although the role of environmental factors is not certain, there may be
an infective agent acquired in childhood, which after years of latency evokes or contributes to the
causation of the immune response. This infective agent can be a modified virus which can infect
genetically susceptible persons. Finally immunocytochemical studies indicate that the
inflammatory cells found in the acute lesions are T4 (helper-inducer) and T8 (suppressorcytotoxic) lymphocytes, suggesting a strong immunologic mechanism of myelin destruction in
which the oligodendrocyte may be the primary target. There is also extensive literature
suggesting that abnormalities in the immune system have an important role in mediating MS
attacks. There is also evidence of good therapeutic response to immunomodulatory therapies
which can reduce number of relapses, burden of white matter disease detected by MRI, slow
disease progression, and disability.
Pathology
The lesions of MS consist of scattered, multiple, sharply delineated areas of demyelination found
anywhere in the CNS white matter but predominantly in the periventricular areas, spinal cord,
brain stem, optic nerves, and optic chiasm. When observed under the microscope there is loss of
myelin with relative preservation of axons and degeneration and absence of myelin producing
cells (oligodendroglia). The amount of mononuclear perivascular cell reaction and edema (acute
lesions) and glial proliferation (chronic lesions) varies with the age of the lesion. Lesions can
occur in major pathways without recognizable clinical symptoms.
Laboratory Tests
Although the diagnosis is usually established on a clinical basis, confirmatory laboratory tests
can assist in some MS cases. CSF studies: In fewer than one third of the patients there can be
Essentials of Clinical Neurology: Demyelinating Disease
LA Weisberg, C Garcia, R Strub
www.psychneuro.tulane.edu/neurolect/
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some modest mononuclear pleocytosis in the CSF, usually fewer than 50 cells/mm3 in the acute
phase of the illness. One third of the patients have a mild increase in CSF protein content,
usually not more than l00mg/dl. In 60% of patients, quantitation of gamma globulin by radioimmunodiffusion shows an increase in the percentage of total CSF protein (normal 12%).
Electro-immunodiffusion shows that IgG is elevated out of proportion to the albumin in CSF in
90% of MS patients. High-resolution agarose electroimmunodiffusion shows that migration
patterns of IgG segregate into discrete bands, known as oligoclonal IgG bands, very early in the
disease in 85% to 95% of patients with definite MS. Although elevation of CSF gamma globulin
with normal CSF protein content is not specific for MS and can be seen in systemic lupus
erythematosus, sarcoidosis, subacute sclerosing panencephalitis, neurosyphilis, and chronic CNS
infections, it can be helpful in establishing the diagnosis when found in a patient who has a
normal serum protein electroimmunodiffusion and clinical evidence of the disease. Myelin basic
protein and anti-myelin oligodendrocyte glycoprotein have been detected in the CSF of MS
patients during acute attacks. Electrophysiologic studies: These are helpful in the diagnosis of
MS and include pattern shift visual (PSVER), brain-stem auditory (BAER), and short latency
somatosensory (SER) evoked potentials. All these tests measure impulse conduction times in the
white matter tracts, which are prolonged or delayed in 60% of MS patients. These tests can also
detect subclinical lesions and can provide additional evidence for diagnosis of multiple lesions.
Imaging studies: Computerized tomography (CT) scans (Figure 21-1) in acute MS can reveal
periventricular and deep white matter contrast-enhanced lesions that evolve into low density
"old" lesions or resolve to normal white matter density. Magnetic resonance imaging (MRI) is
far more sensitive than CT in detecting MS lesions (Figure 21-2). Important MRI criteria
include: (1) multiple periventricular and juxtacortical lesions seen on T-2 weighted image; (2)
infratentorial and corpus callosal lesions: (3) gadolinium enhancing lesions. Although none of
the tests described above are specific for the diagnosis of MS, one or several abnormal results
along with the clinical features can help in reaching an accurate diagnosis. Also, diagnostic
studies should exclude other conditions that might offer a better explanation for the clinical
symptoms and signs in the individual case.
Differential Diagnosis
In the differential diagnosis of MS with lower extremity motor dysfunction, hyperactive reflexes,
Babinski signs, spasticity with autonomic and sensory dysfunction, spinal cord lesions, including
tumors, myelopathy caused by cervical spondylosis, and spinocerebellar degeneration, have to be
considered. Chiari malformation type I and platybasia with basilar impression of the skull with
compression of the brain stem and upper spinal cord should be considered. All of these diseases
can be diagnosed by clinical findings and ancillary laboratory tests. Probably one of the most
important diseases that is difficult to differentiate from MS is systemic lupus erythematosus
involving the CNS. Cerebral, spinal cord, or optic nerve microinfarcts caused by arteriolar
fibrinoid necrosis with multifocal involvement can also be the first manifestation of lupus.
Ancillary laboratory tests including erythrocyte sedimentation rate and antinuclear antibodies
may be needed to differentiate lupus from MS.
Treatment
Treatment with immunomodulating medication is the most effective therapy. The spontaneous
remitting nature of the disease makes evaluation of therapy somewhat difficult. However, the
Essentials of Clinical Neurology: Demyelinating Disease
LA Weisberg, C Garcia, R Strub
www.psychneuro.tulane.edu/neurolect/
21-5
important role that the immune system has mediating relapses of the disease has prompted
several immunomodulating and immunosuppressive therapy trials. These medications used to
treat MS include interferon-beta 1b (Betaseron), beta-1a interferon (Avonex, Rebif), glatiramir
acetate (Copaxone) and high dose intravenous methylprednisolone. Immunosuppressive
medications include mitoxantrone, azathioprine, cytoxan, cyclosporine.
The goals of therapy include: (1) reducing frequency of attacks in relapsing-remitting
condition; (2) reducing severity of neurological impairment; (3) decreasing disease burden as
seen on MRI; (4) preventing evolution to secondary progressive MS and reducing disability of
neurological impairment.
Remember, multiple exacerbations can lead to progressive
neurological impairment and disability. There is evidence that initiating therapy with interferonbeta 1a during the first demyelinating episode of clinically isolated syndromes in which patients
have brain or spinal cord MRI evidence of demyelination delays conversion to clinically definite
MS, even if patient's clinical symptoms and signs show no evidence of dissemination of lesions
in space. In patients with relapsing-remitting MS, interferon and copolymer are effective in
reducing number of attacks, neurological burden of disability and MRI abnormalities. In patients
with acute worsening of neurological symptoms, high-dose methylprednisolone is effective in
reducing neurological disability; however, this should be short course to avoid corticosteroid side
effects. There is evidence that monthly infusions of anti-neoplastic medication, mitoxantrone, is
effective in reducing relapses; however, risk of cardiac toxicity, alopecia, leukopenia must be
considered. In patients with primary progressive MS, which may have different mechanism
(more axonal atrophy than demyelination), no therapy has been shown to be effective. In
patients with relapsing-remitting MS who convert to secondary progressive MS, the role of
therapy has not been demonstrated to be effective, although interferon, mitoxantrone and other
immunosuppressive medication has shown promise in treatment. The role of restorative,
neuroprotective, remyelination, and repair strategies including neurotrophic factors, glutamate
antagonists, bone marrow, stem cell transplantation are undergoing investigation.
Complications of MS include fatigue, spasticity, ataxia, tremor, pain, bowel, bladder, and
sexual dysfunction. Fatigue is the feeling of exhaustion following activity; this exceeds what
might be expected for the level of activity and severity of neurological impairment. It is the most
common symptom of MS, and patient's report it is their worst problem. Fatigue is most common
problem to interfere with vocational capability and is the major reason for vocational disability.
Fatigue is exacerbated by heat. Fatigue may be worsened by several factors - complicating
medical conditions, medication effect, depression, and sleep disorders. Therapy with
amantadine, pemoline, or modafinil have been effective, but medication effect rapidly wears off.
Spasticity with muscle hypertonia reduces functional muscular activity; this frequently interferes
with gait; treatment includes active physical therapy, correct limb positioning, and medication
(tizanidine, baclofen, dantrolene, diazepam, botulinum toxin A). Ataxia and tremor due to
cerebellar functional impairment may affect limbs and trunk and may be worsened by weakness
and spasticity. Treatment with medication is ineffective and management depends upon
physiotherapy techniques. It is believed that MS is a "painless" disease; however, pain may be
serious problem due to demyelination of pain-conducting pathways, e.g., trigeminal neuralgia,
painful tonic spasms. Pain is neuropathic and best treated with antiepileptic and tricyclic
antidepressants. Following urinary tract infections, painful tonic spasms can develop in neck and
back. Bladder problems related to urine storage and emptying are common in MS; urinary
urgency is due to detrusor hyperreflexia. Treatment with anti-cholinergic medication
(tolterodine, oxybutynin, propantheline) are most effective.
Bowel problems include
Essentials of Clinical Neurology: Demyelinating Disease
LA Weisberg, C Garcia, R Strub
www.psychneuro.tulane.edu/neurolect/
21-6
constipation and may be due to immobility, reduced water intake, side effects of other
medication. Management includes attempts to regularize bowel function, enhancing dietary
fiber, and lastly, medication. Sexual dysfunction is related to behavioral factors, and physical
disability (weakness, spasticity, erectile dysfunction) and in certain cases, responds to sildenafil
(Viagra).
NEUROMYELITIS OPTICA (DEVIC'S DISEASE)
Neuromyelitis optica is a transverse or ascending myelitis followed or preceded by acute or
subacute blindness in one or both eyes. It is a rare form of demyelination usually seen in young
patients. The spinal cord, most often at the upper thoracic level, is usually necrotic, with nerve
cell and axon destruction. The necrosis is probably produced by a demyelinating process with
edema and circulatory impairment. Identical lesions have been found in typical cases of MS, and
the optic nerve demyelination is indistinguishable from that in MS. Typical MS plaques have
been found outside the spinal cord and optic nerves in typical cases of neuromyelitis optica, and
some patients have clinical manifestations and autopsy findings of chronic relapsing MS. All
these features suggest that neuromyelitis optica is an acute form of MS. The treatment consists of
high dose methylprednisolone.
OPTIC NEURITIS
In optic neuritis, there is diminution of vision, scotomata, or complete blindness that is usually
sudden and unilateral. Rarely both optic nerves are involved at different time. It usually affects
young patients. Frequently there is ocular or retroocular pain. If the demyelinating lesion is
limited to the optic nerve and the optic disk and retina appears normal, the process is known as
retrobulbar neuropathy or, less appropriately, retrobulbar neuritis. If the demyelinating lesion is
near the nerve head, the disc margins can be blurred and surrounded by hemorrhage so-called
papillitis. Decreased visual acuity differentiates this lesion from papilledema. Papillitis and
retrobulbar neuropathy are frequently associated with painful eye movements. Resolution of the
lesion occurs in most patients. In some patients there is progression to MS; conversely, most
patients with established MS have optic nerve involvement. If surrogate markers of MS activity
such as MRI, CSF and evoked potentials (other than visual) are abnormal, it is highly likely that
these patients will develop signs of MS. Simultaneous occurrence of bilateral optic neuritis
usually suggests a toxic-nutritional cause rather than MS. Gradual, rather than acute onset of
visual symptoms, suggest optic nerve mass lesion or alternative etiology such as Leber's optic
atrophy.
The Longitudinal Optic Neuritis Study showed that 250 mg of intravenous
methylprednisolone four times daily for 3 days, followed by oral prednisone 1 mg/kg for 11 days
and tapered over 3 days gives a 57% reduction of new clinical neurologic attacks. The study also
showed that oral prednisone alone was of no benefit. Certain cases of optic neuritis are
associated with corticosteroid-responsive autoimmune disorders including systemic lupus
erythematosus.
ACUTE DISSEMINATED ENCEPHALOMYELITIS
Acute disseminated encephalomyelitis is a rare demyelinating disease that is usually monophasic
and self-limiting and preceded or accompanied by some viral exanthematous infection such as
chickenpox, measles, smallpox, rubella, or a nonspecific respiratory infection (so-called
Essentials of Clinical Neurology: Demyelinating Disease
LA Weisberg, C Garcia, R Strub
www.psychneuro.tulane.edu/neurolect/
21-7
postinfectious or parainfectious encephalomyelitis). The same type of disease can be precipitated
by vaccination against rabies or smallpox (so-called postvaccinal or allergic encephalomyelitis).
Although a viral infection precedes or is associated with the disease, no virus has been isolated
from the CSF or brain tissue, and the histopathologic changes are different from those in viral
encephalomyelitis and most closely resemble the central nervous system lesions seen in
experimental allergic encephalomyelitis. An immune-mediated complication of infection seems
most likely. Foci of demyelination around veins, which are cuffed by lymphoreticular cells, are
disseminated throughout the cerebrum, brain stem, cerebellum, and spinal cord. Clinically there
is an acute onset of somnolence, confusion, and meningeal signs followed by ataxia, involuntary
movements, convulsions, or coma. Paraplegia or quadriplegia can occur when the spinal cord is
involved. The mortality varies from 10% to 50%. Complete recovery occurs in some patients;
others can have permanent sequelae such as epilepsy, behavioral problems, or permanent motor
deficit. Treatment with corticosteroids (see earlier protocol) seems to reduce the severity of the
disease. Anticonvulsants should be used when needed. Atypical cases that are "transitional"
between acute disseminated encephalomyelitis and MS have been observed, probably implying
some common immune mechanism. It is impossible to differentiate clinically between acute MS
and acute disseminated encephalomyelitis.
SUMMARY
Demyelinating diseases are a group of acquired disorders of unknown cause that affect the CNS
myelin. They should be differentiated from other disorders that also affect the myelin as a
secondary phenomenon, such as some genetic metabolic disorders (leukodystrophies), toxicmetabolic conditions (sub-acute combined degeneration and central pontine myelinolysis),
hypoxia, and so on. The acute forms include acute disseminated encephalomyelitis, optic
neuritis, and neuromyelitis optica. Some patients with the acute forms respond to high dose
steroid treatment. The chronic form, or MS, has a relapsing-remitting course with progressive
neurologic impairment and poor response to treatment. The important role that the immune
system has mediating relapses of the disease has prompted several immunosuppressive therapy
trials that have lessened the frequency of MS attacks.
Suggested Readings
Multiple Sclerosis—General
Compston A: Multiple Sclerosis. Lancet 359:1221 2002.
Constant CF: Pathogenesis of multiple sclerosis. Lancet 343:271, 1994.
O'Connor P: Key issues in 2002: The diagnosis and treatment of MS. Neuro (suppl 3)59:S-1,
2002.
Poser CM: Trauma to CNS may result in formation or enlargement of MS plaques. Arch Neuro
57:1074, 2000.
Simon JH, Thompson AJ: Is MS still a clinical diagnosis? Neurology 61:596, 2003.
Sobel RA: The pathology of multiple sclerosis. Neurol Clin North Am 13:1, 1995.
Essentials of Clinical Neurology: Demyelinating Disease
LA Weisberg, C Garcia, R Strub
www.psychneuro.tulane.edu/neurolect/
21-8
Optic Neuritis
Beck RB, Cleary PA, Anderson MN: A randomized controlled trial of corticosteroids in
treatment of optic neuritis. N Engl J Med 326:581, 1992.
Beck RW: The effect of corticosteroids for acute optic neuritis on the subsequent development of
multiple sclerosis. N Engl J Med 329:176, 1993.
Optic Neuritis Study Group: The 5-year risk of MS after optic neuritis. Neurology 49:1404,
1997.
Transverse Myelitis
Transverse Myelitis Consortium Working Group: Proposed diagnostic criteria and nosology of
acute transverse myelitis. Neurology 59:499, 2002.
Multiple Sclerosis—Clinical
Birk K: The clinical course of MS during pregnancy and puerperium. Arch Neurol 47:738,
1990.
Filippi M, Grossman RI: MRI techniques to monitor MS evolution. Neurology 58:1147, 2002
Kujalaj P, Portin R, Ruutiainen J: The progress of cognitive decline in MS. Brain 120:289,
1997.
Kurtzke JF: Rating neurologic impairment in multiple sclerosis: an Expanded Disability Status
Scale (EDSS). Neurology 33:1444, 1983.
McDonald WI: Recommended Diagnostic Criteria for Multiple Sclerosis: Guidelines from the
International Panel on the Diagnosis of MS. Ann Neuro 50:121, 2001.
O'Riordan JI, Thompson AJ: The prognostic value of brain MRI in clinically isolated syndromes
of MS. Brain 121:495, 1998.
Poser CM: New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann
Neurol 13:227, 1983.
Multiple Sclerosis—Treatment
Ebers GC: Treatment of multiple sclerosis. Lancet 343:275, 1994.
Hunter SF: Rational clinical immunotherapy for Multiple Sclerosis. Mayo Clin Proc 72:765,
1997.
Jacobs LD, Beck RW: Intramuscular interferon-beta 1a therapy initiated during a first
demyelinating event in MS. NEJM 343:898, 2000.
Report of the Quality Standards Subcommittee of the American Academy of Neurology:
Practice advisory on selection of patients with multiple sclerosis for treatment with Betaseron.
Neurology 44:1537, 1994.
Rudick RA, Cohen JA: Management of MS. NEJM 337:1604, 1997.
Rudick RA: Disease modifying drugs for relapsing-remitting MS and future directions for MS
therapeutics. Arch Neuro 56:1079, 1999.
Silverberg DH: Multiple sclerosis: approaches to management. Ann Neurol 36(suppl):l, 1994.
The IFNB MS Study Group: Interferon-beta 1b is effective in relapsing-remitting MS.
Neurology 43:655, 1993.
Tselis AC, Lisak RP: Multiple sclerosis: therapeutic update. Arch Neuro 56:277, 1999.
Essentials of Clinical Neurology: Demyelinating Disease
LA Weisberg, C Garcia, R Strub
www.psychneuro.tulane.edu/neurolect/
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Neuromyelitis Optica
Wingerchuck DM, Hogancamp WF: The clinical course of neuromyelitis optica. Neurology
53:1107, 1999.
Acute Disseminated Encephalomyelitis
Kepes JJ: Large focal tumor-like demyelinating lesions of the brain: intermediate entity between
MS and acute disseminated encephalomyelitis. Ann Neuro. 33:18, 1993.
Complications of MS
Logsdail SJ: Psychiatric morbidity in patients with MS. Psychol Med 18:355, 1988.
Mohr DC: Course of depression during interferon therapy in MS. Neurology 56:1263, 1999.
Sadovaick AD: Depression and MS. Neurology 46:629, 1996.
Sheean GL, Murray NMF: An electrophysiological study of mechanisms of fatigue in MS.
Brain 120:299, 1997.
Essentials of Clinical Neurology: Demyelinating Disease
LA Weisberg, C Garcia, R Strub
www.psychneuro.tulane.edu/neurolect/
A
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B
FIGURE 21-1.
CT scan shows bilateral periventricular (A) and subcortical white matter (B) hyperdense lesions
(arrows) consistent with demyelination of the MS type.
A
B
C
FIGURE 21-2.
MRI scan shows multiple high-signal intensity periventricular (A) and subcortical white matter
(B) lesions consistent with MS. There is also a right pontine lesion (arrow) (C) not seen on the
CT scan. See legend.