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From:  "s_laliberte_2001" <http://health.groups.yahoo.com/group/= BreastImplants_MultipleSclerosis/post?postID=3DMwKEsXBx25EP0u3RudJ01FzcZA= s4H7XyLyoe951mO3Anmkg1yvivWHFtB0O4PKCEzU9oXys97lLoZpky739gIxwm>=20
Date: =20 Mon Dec 2, 2002  9:50 am
Subject:  Multiple=20 Sclerosis

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Multiple=20 Sclerosis

Last Updated: December 10, 2001
Rate = this=20 Article
Email to a Colleague




AUTHOR=20 INFORMATION
Section 1 of 11
Author Information = Introduction=20 Clinical Differentials Workup
Treatment Medication=20 Follow-up
Miscellaneous Pictures=20 Bibliography



Author: Marjorie Lazoff, MD, = Medical=20 Editor, Medical Computing Today;
Contributing
Editor, = MSR's=20 NetView
Marjorie Lazoff, MD, is a member of the following = medical=20 societies:
Alpha Omega
Alpha, American College of = Emergency=20 Physicians, and Society for
Academic
Emergency=20 Medicine
Editor(s): Edmond Hooker, MD, Assistant Clinical = Professor, Department
of
Emergency Medicine, = University of=20 Louisville, Wright State = University;
Francisco
Talavera,=20 PharmD, PhD, Senior Pharmacy Editor, Pharmacy, eMedicine;=20 J
Stephen
Huff, MD, Associate Professor of Emergency = Medicine=20 and Neurology,
Department of
Emergency Medicine, = University of=20 Virginia Health System; John
Halamka, MD, = Chief
Information=20 Officer, CareGroup Healthcare System, Assistant = Professor
of=20 Medicine,
Department of Emergency Medicine, Beth Israel = Deaconess=20 Medical
Center; Assistant
Professor of Medicine, = Harvard=20 Medical School; and Craig Feied, MD,
FACEP,
FAAEM, = Director of=20 Informatics, Department of Emergency=20 Medicine,
Washington
Hospital Center; Clinical = Associate=20 Professor, Department of Emergency
Medicine,
George = Washington=20 University; Director, National Center for=20 = Emergency
Medicine
Informatics


INTRODUCTION
Section=20 2 of 11
Author Information Introduction Clinical = Differentials=20 Workup
Treatment Medication Follow-up
Miscellaneous = Pictures=20 Bibliography



Background: Multiple sclerosis = (MS) is=20 an idiopathic inflammatory
demyelinating disease = of
the CNS.=20 Patients with MS commonly present with an individual mix=20 of
neuropsychological
dysfunction, which tends to = progress=20 over years to decades.

The diagnosis of MS is based = on a=20 classic presentation (ie, optic
neuritis, = transverse
myelitis,=20 internuclear ophthalmoplegia, paresthesias) and on=20 the
identification of other
neurologic abnormalities, = which=20 may be indicated by the patient
history and exam.=20 Typical
findings on an MRI also help establish a = diagnosis of=20 MS.

Patients with atypical presentations and/or a = normal or=20 atypical MRI
may require evoked
potential studies, to = uncover=20 subclinical neurologic abnormalities, or
cerebral spinal=20 fluid
(CSF) analysis, which also serves to exclude = treatable=20 disorders and
document MS-like
immune activity in the=20 CNS.

By convention, the confidence in the diagnosis = of MS is=20 described as
definite, probable, or
possible MS. It = includes a=20 classification with respect to clinical
presentation,=20 which
correlates somewhat with the prognosis and is = useful in=20 clinical
trials.

About 70% of patients present = with the=20 more favorable
relapsing-remitting (RR) type, which=20 is
characterized by acute exacerbations with full or = partial=20 remissions.

For patients with RR, the FDA has = approved the=20 long-term use of
beta-interferons and
glatiramer = acetate,=20 which is a synthetic form of myelin basic protein
(MBP) = that has=20 fewer
side effects than interferon. In rigorous trials = that had=20 different
end points, both demonstrated
reductions of=20 approximately 33% in both clinical disease activity=20 and
progression of MS
lesions on MRI. Opinions vary on = when in=20 the course of MS to initiate
treatment with = these
agents. The=20 literature favors beta-interferons, although = adverse
effects are=20 more troublesome
than with glatiramer acetate. Research = is active=20 and ongoing.

The remaining patients present with = chronic=20 progressive MS, which is
subdivided further into
(a)=20 primary-progressive (PP), (b) relapsing-progressive (RP), = which=20 is
a pattern combining
features of RR and RP and is=20 intermediate in clinical severity, and
(c)=20 secondary-progressive
(SP), which many patients with RR = progress=20 to over time.

Treatment for those with chronic = progressive MS=20 is less satisfying
than for those with RR.
Patients = with SP=20 type may respond to beta-interferons, and one study
found = modest=20 impact
on disease progression when the patients were = given a low=20 dose of
methotrexate.

The group of idiopathic = inflammatory=20 demyelinating syndromes,
including MS, is shown = in
Table 1 at=20 the end of this article. Emergency physicians should = be
familiar=20 with optic neuritis,
acute transverse myelitis, and acute = disseminated encephalitis. In any
given patient, = each
syndrome=20 may be unrelated to MS, or it may be a presenting symptom = or
an=20 exacerbation of
MS.Not included in Table 1 are 2 other = clinical=20 syndromes that share
features of MS and
may represent = 2=20 opposite ends of the MS spectrum.

Acute fulminant MS, = which=20 often results in death or extensive
morbidity within=20 days

A forme fruste or benign MS with = uncharacteristically=20 slow, if any,
disease
progression over the=20 decades

Patients with established MS may present to = the ED=20 because of a
relapse or because of
complications of MS = (eg,=20 bladder dysfunction, impaired swallowing or
cough reflex, = prolonged
immobilization, nutrition/hydration = complications,=20 adverse effects of
medication). Of those
that present = because=20 of a relapse, 80% have exacerbations of previous,
rather = than=20 new,
deficits.

ED assessment includes the = elimination of=20 other treatable etiologies
and a search for = known
precipitants=20 of relapses (eg, fever, exercise, infection). Ruling=20 out
asymptomatic urinary tract
infection (UTI) in = patients=20 with MS and distinguishing the flulike
symptoms that may=20 occur
with chronic interferon therapy from a true = infection are=20 important.
No firm correlation exists
between MS = exacerbations=20 and trauma, allergic responses, immunization,
or physical = or
emotional stress, but this remains especially=20 controversial.

The development of new focal deficits = in a=20 patient without known MS
can be a = diagnostic
challenge.=20 Patients who present with optic neuritis, = transverse
myelitis,=20 disseminated
encephalitis, or other signs and symptoms = that are=20 evocative of MS
require exclusion of
treatable = etiologies.=20 However, confirmation or exclusion of MS lies
outside the = scope=20 of ED
evaluation. Determining the extent of ED evaluation = and the=20 need for
admission versus
outpatient referral often is = a=20 judgment call.

Pathophysiology: MS is regarded as an=20 autoimmune disease. Most of what
is known about
MS is = derived=20 from its model in animal research, which is=20 experimental
allergic
encephalomyelitis.

The=20 autoantigen in MS most likely is one of several myelin=20 proteins
(eg, proteolipid protein
[PLP], myelin=20 oligodendrocyte glycoprotein [MOG], MBP). = Microglial
cells and=20 macrophages
perform jointly as antigen-presenting cells,=20 resulting in activation
of cytokines, complement,
and = other=20 modulators of the inflammatory process, targeting=20 specific
oligodendroglia cells
and their membrane=20 myelin.

The pathologic hallmark of MS is = multicentric,=20 multiphasic CNS
inflammation and
demyelination. = Originally,=20 each MS lesion was thought to evolve
through episodes=20 of
demyelination and remyelination into a chronic = burned-out=20 plaque with
relative preservation of
axons and = gliosis. Thus,=20 the neuropsychological dysfunction occurred,
despite an=20 essentially
intact neural network, until late in the = disease=20 course. However,
recent studies have
demonstrated that = axonal=20 transections do occur during acute
exacerbations;=20 furthermore,
axonal damage, as measured by magnetic = resonance=20 spectroscopy, was
found to correlate
with clinical = disability.=20 Clearly, more work is needed to understand
the = associations=20 among
inflammation-mediated demyelination, axonal injury, = and=20 clinical
disability.

For unclear reasons, lesions=20 characteristically involve the optic
nerve and = periventricular=20 white
matter of the cerebellum, brain stem, basal = ganglia, and=20 spinal cord.
Identifying MS lesions
in gross specimens = is=20 difficult, as is identifying MS lesions in gray
matter on = radiographic
images; hence, the predilection for white = matter may=20 not be disease
related. The peripheral
nervous system = rarely=20 is involved.

Frequency:

In the US: MS is the = most=20 common debilitating illness among young
adults. = The
incidence=20 is 0.5-1 per 1000 people, and the general population has = a
0.2%=20 lifetime
risk of acquiring MS. Approximately 25,000 new = cases are=20 diagnosed
each year.

Internationally: = Approximately 1 per=20 1,000,000 people acquire = MS.

Mortality/Morbidity:

MS=20 affects quality of life rather than duration of=20 life.

Worsening disability from any cause is strongly = associated with
increased = mortality
rate.

Deaths=20 attributable to MS are the result of fulminant MS, which = is
rare;=20 complications
from chronic disability (eg, pneumonia, = pulmonary=20 embolism, infected
decubiti);=20 and
suicide.

Race:

Incidence is higher in=20 Caucasians than in other races for which
incidences are=20 known.
The incidence may be twice as high in Caucasians = as in=20 other races.

MS essentially is unknown among Eskimos = and=20 Bantus, and it is rare
among Native
Americans and=20 Asians.

MS is 5 times more prevalent in temperate = climates=20 than in the
tropics, but the risk
seems to be = associated=20 entirely with childhood years spent in a
temperate=20 climate.
The risk of acquiring MS is higher in those who = have=20 lived in a
temperate climate
before age 15, but not in = those=20 who move to a temperate climate after
age=20 15.

Sex:

Throughout adulthood the = female-to-male ratio=20 is 2:1.

The sex ratio is more pronounced in those = younger=20 than 16 years (ie,
approaches
3:1), but it is less = pronounced=20 in those older than the fifth decade.

On average, men = present=20 1-2 years later than women, and men have = a
greater
tendency=20 for having the progressive disease at onset.

Age: MS = rarely=20 occurs in those younger than 20 years or those older
than = 50=20 years. The
occurrence of MS is even more rare in those = younger=20 than 15 years and
in those older than
60=20 years.

CLINICAL
Section 3 of 11
Author = Information=20 Introduction Clinical Differentials Workup
Treatment = Medication=20 Follow-up
Miscellaneous Pictures=20 Bibliography



History: The review of systems = should=20 concentrate on the evidence of
bladder, kidney, = lung,
or skin=20 infection and irritative or obstructive bladder=20 symptoms.

Classic MS symptoms

Sensory loss = (ie,=20 paresthesias) usually is an early complaint.

Motor = (eg,=20 muscle cramping secondary to spasticity) and autonomic=20 (eg,
bladder, bowel, sexual dysfunction) spinal cord = symptoms may=20 be
present.

Cerebellar symptoms (eg, Charcot triad = of=20 dysarthria, ataxia, = tremor)
may
occur.

Constitutional=20 symptoms, especially fatigue (which occurs in 70%=20 of
cases)
and dizziness, may be = present.

Subjective=20 difficulties with attention span, concentration,=20 memory,
and
judgment may be noted any time during the = disease=20 course.

About 50% of patients with MS have = impairment,=20 usually mild, in
information
processing on = neuropsychological=20 testing.

Depression is common, but euphoria is less=20 common.

Over the course of the disease, 5-10% of = patients=20 develop an overt
psychiatric
disorder (eg, manic = depression,=20 paranoia, major depression) or
dementia.

Eye = symptoms,=20 including diplopia on lateral gaze, occur in 33%=20 of
patients.

Trigeminal neuralgia may = occur.

Optic=20 neuritis (ON) (ie, inflammation or demyelination of optic=20 nerve)
is the initial
presentation of 15% of patients = with MS.=20 Fifty percent of all patients
who present with
ON have = MS.=20 Isolated episodes of ON, even if they are recurrent, = do
not=20 represent
MS.

Acute onset (ie, occurring over = minutes or=20 hours, rarely days) of
single eye
visual blurring, = decreased=20 acuity (ie, usually scotoma), = decreased
color
perception,=20 and/or discomfort of the moving eye(s) are symptoms=20 that
are
indicative of ON.

The 3 phenomena = associated=20 with ON or compressive/ischemic neuritis
are=20 as
follows:

Phosphenes, or flashes of light, = usually are=20 precipitated by eye
movements.

Uhthoff phenomenon = or=20 deterioration of vision is induced by exercise,
a
hot = meal, or=20 a hot bath.

The Pulfrich effect occurs when latencies = between=20 the eyes are
unequal,
resulting in a sense of = disorientation=20 in moving traffic.

Acute transverse = myelitis

Partial=20 acute transverse myelitis, rather than total, usually is=20 a
manifestation of
MS. Strongly consider mechanical=20 compression in the differential
diagnosis.

Acute = partial=20 loss of motor, sensory, autonomic, reflex, and=20 sphincter
function
below the level of the lesion = indicates=20 acute transverse myelitis.

Devic syndrome is acute = transverse=20 myelitis accompanied by bilateral
ON.

Acute = disseminated=20 encephalitis is pathophysiologically and
radiographically = identical
to MS. It is characterized by acute onset of = motor,=20 sensory,
cerebellar, and cranial
nerve dysfunction = with=20 encephalopathy, progressing to coma and
eventual death = in
30%=20 of such cases.

MS as a sole symptom is unusual, but = MS may=20 present with many other
typical MS
presentations, = including=20 the following:

Aphasia or=20 dysphasia

Hemianopsia

Seizures (5% of patients = with=20 MS)

Significant motor complaints without sensory = deficits or=20 dysautonomia
(eg,
bladder)

Physical: Classic MS = findings on neurologic examination include=20 the
following:

Eye

Optic = neuritis

Acutely,=20 50% of patients present with retrobulbar involvement;=20 hence,
funduscopy results are normal. "The patient sees = nothing=20 and the
doctor
sees nothing."

Anterior = involvement=20 causes papillitis, and differentiating this = from
papilledema is=20 important. When inflammation involving the retina = is
extensive,=20 look for presence of a macular star.

After several = weeks,=20 optic atrophy may be seen.

An afferent pupillary = defect may=20 be seen in the affected eye.

Visual acuity usually is = impaired (ie, subtle to total blindness).

The classic = finding=20 is bilateral (unilateral much less=20 common)
internuclear
ophthalmoplegia (INO), a lesion = in the=20 median longitudinal fasciculus
(MLF)
resulting in a = weakness=20 in adduction of the ipsilateral eye with
nystagmus=20 on
abduction of the contralateral eye, an incomplete or = slow=20 abduction of
the
ipsilateral eye upon lateral gaze, = with=20 complete preservation of
convergence.

Other eye = findings=20 include abnormal pupillary responses,=20 acquired
pendular
nystagmus or sinusoidal involuntary=20 oscillations of one or both eyes,
and/or
loss of = smooth eye=20 pursuit.

Regardless of the stage or classification, = most=20 authorities question
the
diagnosis of MS in a patient = without=20 at least one of these findings.

Spinal cord=20 involvement

Acute transverse = myelitis

Sphincter=20 paralysis and unchanging level

Distinguish from=20 Guillain-Barr=E9 syndrome

Paralysis, spasticity, and=20 hyperreflexia are indicative of upper = motor
neuron
dysfunction=20 (ie, lateral corticospinal tracts). Decreased = joint
position=20 and
vibration sense (ie, dorsal columns) are common=20 findings.

Decreased pain and temperature (ie, lateral = spinothalamic tracts) are
less
common. The sparing of = these=20 symptoms may be diagnostically helpful.

The degree of = corticospinal tract findings tends to correlate = with
bladder,=20 bowel,
and sexual dysautonomias.

Cerebellar = findings:=20 Disequilibrium, truncal or limb ataxia, scanning
(ie,=20 monotonous)
speech, intention tremor, and saccadic = dysmetria are=20 common cerebellar
findings.

Lhermitte sign: Neck = flexion=20 results in an electric shocklike feeling
in the torso=20 or
extremities

Acute disseminated = encephalitis

Most=20 commonly, altered mental status and/or personality=20 changes

Focal findings (eg, cranial nerve defects,=20 hemiparesis, focal
seizures,
autonomic=20 dysfunction)

Cranial nerve=20 defects

Ataxia

Dysphasia

Meningismus, = usually=20 less common and pronounced than in meningitis

Unusual = findings in MS include the absence of eye findings = and
isolated=20 motor,
sensory, cerebellar, and cranial nerve=20 lesions.

Causes: MS commonly is believed to result = from an=20 autoimmune process.
What triggers the
autoimmune = process is=20 not clear, but the nonrandom nature of its
geographic=20 distribution
suggests an isolated or additive = environmental=20 effect and/or
inadvertent activation and
dysregulation = of CNS=20 immune processes by a retroviral infection that
was = perhaps=20 acquired
in childhood. On the basis of bench research = findings,=20 some
authorities implicate human
herpesvirus-6 (HHV-6) = variant=20 B group 2, while others implicate
Chlamydia=20 pneumonia.

Polygene inheritance accounts for a = familial rate=20 of 10-20%; yet, most
studies confirm that = a
monozygotic twin=20 has only a 30% risk of acquiring MS, suggesting a
genetic = predisposition
to an environmental viral agent.

As = in=20 systemic lupus erythematosus (SLE), human leukocyte = antigen
(HLA)=20 patterns of
patients with MS tend to differ from those of = the=20 general population.

Although no present studies = support a=20 connection between hepatitis B
vaccination and = MS,
worldwide=20 anecdotal reports prompted the Centers for Disease = Control
and=20 Prevention (CDC)
to investigate this possibility (see CDC = web=20 site
http://ww= w.cdc.gov/nip/vacsafe/concerns/MS/default.htm).

Optic=20 neuritis is attributable to MS in 50% of cases; the = remaining
50%=20 of cases are
probably postinfectious. Ischemic optic = neuropathy,=20 arteriovenous
malformations,
tumors, and other = compressive=20 lesions usually present more gradually
with=20 additional
symptoms or atypical features, but these = complications=20 should be
pursued
aggressively in any patient = presenting with=20 ON.

Acute transverse myelitis, when not attributable = to MS,=20 most likely is
infectious (eg,
Epstein-Barr virus = [EBV], Lyme=20 [rare]) or postinfectious. An important
ED exclusion = in
these=20 patients is mechanical compression by tumor, abscess,=20 or
aneurysm.

Acute disseminated encephalitis = involves a=20 poorly defined
immune-mediated
demyelinating=20 process.


DIFFERENTIALS
Section 4 of = 11
Author=20 Information Introduction Clinical Differentials = Workup
Treatment=20 Medication Follow-up
Miscellaneous Pictures=20 Bibliography



Amyotrophic Lateral = Sclerosis
Bell=20 Palsy
Brain Abscess
Guillain-Barr=E9 Syndrome
HIV = Infection=20 and AIDS
Lumbar (Intervertebral) Disk Disorders
Neck=20 Trauma
Sarcoidosis
Spinal Cord Infections
Spinal = Cord=20 Injuries
Stroke, Hemorrhagic
Stroke, = Ischemic
Subdural=20 Hematoma
Syphilis
Systemic Lupus = Erythematosus
Tick-Borne=20 Diseases, Lyme
Transient Ischemic Attack
Trigeminal=20 Neuralgia


Other Problems to be = Considered:

Beh=E7et=20 disease
Brainstem tumors
Central nervous system=20 infections
Cerebellar tumors
Friedreich = ataxia
Hereditary=20 = ataxias
Leukodystrophies
Neurofibromatosis
Pernicious=20 anemia
Progressive multifocal = leukoencephalopathy
Ruptured=20 intervertebral disk
Small cerebral infarcts
Spinal = cord=20 tumors
Syringomyelia
Vasculitides
Quick = Find
Author=20 = Information
Introduction
Clinical
Differentials
Workup
Tre= atment
Medication
Follow-up
Miscellaneous
Pictures
Bibliog= raphy

Click=20 for related
images.


Related = Articles
Amyotrophic=20 Lateral
Sclerosis

Bell Palsy

Brain=20 Abscess

Guillain-Barr=E9
Syndrome

HIV = Infection=20 and
AIDS

Lumbar
(Intervertebral)=20 Disk
Disorders

Neck=20 Trauma

Sarcoidosis

Spinal=20 Cord
Infections

Spinal Cord = Injuries

Stroke,=20 Hemorrhagic


Stroke, Ischemic

Subdural=20 Hematoma


Syphilis

Systemic=20 Lupus
Erythematosus

Tick-Borne
Diseases,=20 Lyme

Transient Ischemic
Attack

Trigeminal=20 Neuralgia

http://www.emedicine= .com/EMERG/topic321.htm







  Replies Name/Email = Yahoo! ID = Date  
787 Multiple=20 Sclerosis s_laliberte_2001=20 <S_laliberte_2001@yahoo. s_laliberte_2001 = Sun  12/8/2002  
1276 Multiple=20 Sclerosis s_laliberte_2001 s_laliberte_2001 = Sun  4/20/2003  =20

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