AUTHOR INFORMATION

Section 1 of 12

Authored by Marjorie Lazoff, MD, Medical Editor, Medical Computing Today; Contributing Editor, MSR’s NetView

Marjorie Lazoff, MD, is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Edited by Edmond Hooker, MD, Assistant Clinical Professor, Department of Emergency Medicine, University of Louisville, Wright State University; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; J Stephen Huff, MD, Associate Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia Health System; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital

Author's Email:	Marjorie Lazoff, MD
Editor's Email:	Edmond Hooker, MD

eMedicine Journal, October 31 2005, VOLUME 6, Number 10

INTRODUCTION

Section 2 of 12

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

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

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

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

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

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

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

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

The group of idiopathic inflammatory demyelinating syndromes, including MS, is shown in Table 1 at the end of this article. Emergency physicians should be familiar with optic neuritis, acute transverse myelitis, and acute disseminated encephalitis. In any given patient, each syndrome may be unrelated to MS, or it may be a presenting symptom or an exacerbation of MS.

Not included in Table 1 are 2 other clinical syndromes that share features of MS and may represent 2 opposite ends of the MS spectrum.

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

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

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

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

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

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

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

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

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

Frequency:

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

• Internationally: Approximately 1 per 1,000,000 people acquire MS.

Mortality/Morbidity:

• MS affects quality of life rather than duration of life.

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

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

Race:

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

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

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

Sex:

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

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

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

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

CLINICAL

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

• Classic MS symptoms

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

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

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

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

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

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

• Depression is common, but euphoria is less common.

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

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

• Trigeminal neuralgia may occur.

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

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

• The 3 phenomena associated with ON or compressive/ischemic neuritis are as follows:
  • Phosphenes, or flashes of light, usually are precipitated by eye movements.

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

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

• Acute transverse myelitis

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

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

• Devic syndrome is acute transverse myelitis accompanied by bilateral ON.

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

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

• Aphasia or dysphasia

• Hemianopsia

• Seizures (5% of patients with MS)

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

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

• Eye

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

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

  • After several weeks, optic atrophy may be seen.

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

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

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

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

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

• Spinal cord involvement

• Acute transverse myelitis
  • Sphincter paralysis and unchanging level

  • Distinguish from Guillain-Barré syndrome

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

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

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

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

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

• Acute disseminated encephalitis

• Most commonly, altered mental status and/or personality changes

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

• Cranial nerve defects

• Ataxia

• Dysphasia

• Meningismus, usually less common and pronounced than in meningitis

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

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

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

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

Although no present studies support a connection between hepatitis B vaccination and MS, worldwide anecdotal reports prompted the Centers for Disease Control and Prevention (CDC) to investigate this possibility (see the CDC Web site Multiple Sclerosis and the Hepatitis B Vaccine).

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

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

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

DIFFERENTIALS

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

Other Problems to be Considered:

Behçet disease
Brainstem tumors
Central nervous system infections
Cerebellar tumors
Friedreich ataxia
Hereditary ataxias
Leukodystrophies
Neurofibromatosis
Pernicious anemia
Progressive multifocal leukoencephalopathy
Ruptured intervertebral disk
Small cerebral infarcts
Spinal cord tumors
Syringomyelia
Vasculitides

WORKUP

Section 5 of 12

Lab Studies:

• CBC with differential

• Serum glucose

• To rule out hypoglycemia and chronic hyperglycemia as causes of neurological findings

• Helps in CSF glucose interpretation

• Serum electrolytes: Determine abnormalities associated with neurologic, muscle, or systemic dysfunction (K⁺, Ca²⁺, P⁺, and Na⁺).

• Coagulation studies prior to lumbar puncture: These are indicated in patients with history of easy bleeding, liver disease, malnutrition, or alcoholism.

• Urinalysis and microscopy

Imaging Studies:

• CT scan of head with contrast

• This imaging study is indicated in the ED to assess focal neurological examination or acute changes in mental status prior to lumbar puncture.

• For all other investigations, MRI is unarguably more sensitive and specific in diagnosing MS and related disorders. In selected patients, MRI will be the preferred imaging study in the ED.

• MRI of head with gadolinium

• Typical MRI findings support the diagnosis (ie, 50% progress to clinically definite MS within 2 years), but 5% of suspected patients with normal MRI findings similarly progress to MS.

• T1 shows active lesions (2-6 weeks) reflecting perivascular inflammation and breakdown of blood-brain barrier (BBB). T2 most commonly shows old lesions in periventricular supratentorial white matter, but old lesions occasionally are seen in the cerebellum and brain stem.

• To visualize the optic nerve, a special MRI technique is required to suppress the fat signal.

• Acute disseminated encephalitis may be radiographically indistinguishable from MS.

• MRI of spine with gadolinium

• For patients with acute transverse myelitis, this is indicated to rule out a compressing lesion.

• For MS lesions of the spine, a special MRI technique is required to obliterate CSF signal on T2-weighted images.

• CT scan of the cervical vertebrae: This is used as a screening test for cervical radiculopathy secondary to trauma and for osteoarthritis.

Other Tests:

• CSF analysis is indicated if diagnosis is uncertain and neurological presentation or neuroimaging raises suspicion of CNS infection.

• Typical findings in MS and acute disseminated encephalitis include 0-50 mononuclear cells on cell count, 25% elevated protein, normal glucose level, selective increase in immunoglobulin G (eg, oligoclonal bands, free kappa chains), and an abnormal colloidal gold curve.

• Some patients with MS will have normal or atypical CSF findings.

TREATMENT

Section 6 of 12

Prehospital Care:

• Evaluate and treat for dehydration. Administer crystalloid infusion until patient is euvolemic.

• Consider airway protection in patients with altered mental status.

Emergency Department Care:

• Medical management goals are to delay onset of MS, slow disease progression, relieve symptoms, and ameliorate risk factors associated with an acute exacerbation. The last 2 goals are sometimes achievable in the ED.

• Fulminant MS or disseminating acute encephalitis

• Stabilize acute life-threatening conditions.

• Initiate supportive care and seizure precautions.

• Monitor for increasing intracranial pressure (ICP).

• Consider emergent plasmapheresis. (A recent study suggested it may be superior to intravenous [IV] steroids in patients with acute fulminant MS.)

• Identify and control known precipitants of MS exacerbation.

• Aggressively treat infections with antibiotics.

• In patients with a fever, normalize the body temperature with antipyretics. (Conduction through partially demyelinated fibers varies greatly with even small increases in temperature.)

• Provide urinary drainage and skin care, as appropriate.

• Preoperative considerations for emergency surgery in patients with MS

• Gastric emptying may be delayed secondary to autonomic GI dysfunction.

• Labile autonomic nervous system may precipitate hypotension during anesthesia and surgery.

• Spontaneous ventilation may be disrupted.

• Anti-inflammatory treatment may shorten an acute exacerbation of MS, but no evidence suggests that it changes the overall disease progression. Anti-inflammatory treatment may be more effective acutely in patients who have predominantly movement involvement rather than sensory involvement. Most common therapy is high-dose pulsed methylprednisolone.

• Anti-inflammatory treatment for ON is very controversial. A multicenter trial showed short-term recovery, but the overall disease course and progression to MS were unchanged after 2 years. Most common therapy is methylprednisolone, followed by oral prednisone. Oral prednisone alone was found to be ineffective and may increase the likelihood of future MS attacks; therefore, avoid prescribing only prednisone.

• Anti-inflammatory treatment for acute transverse myelitis and acute disseminated encephalitis is presented commonly in texts as an option; however, not many supporting data are given. Dexamethasone is a common treatment.

Consultations:

• Neurology

• Ophthalmology, if indicated

• Urology for urodynamics, if indicated

• Home care assessment, if indicated

MEDICATION

Section 7 of 12

Treatment of progressive disease or prevention of relapses may involve use of interferon, cyclosporine, azathioprine, methotrexate, or other immunomodulatory agents. Increasingly, treatment includes combination therapy using 2 or more of these agents. Note that natalizumab (Tysabri), a humanized monoclonal antibody approved in November 2004 to decrease the frequency of exacerbations in RR-MS, was suspended in February 2005 because of 2 postapproved cases of progressive multifocal leukoencephalopathy (PML) when used concomitantly with interferon beta-1a. Use of all these medications is beyond the usual scope of practice of emergency physicians, and they are not discussed further in this section.

Drug Category: Corticosteroids -- Solu-Medrol is used in treatment of acute exacerbations of MS and ON in adults. Dexamethasone is used in the treatment of acute transverse myelitis and acute disseminated encephalitis.

Drug Name	Methylprednisolone (Solu-Medrol) -- Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Adult Dose	High-dose pulsed: 500 mg IV for 5 d A very controversial recent study (Sellebjerg et al, 1998) supports PO regimen of 500 mg for 5 d; then taper over 10 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; viral, fungal, or tubercular skin lesions
Interactions	Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications

Drug Name	Dexamethasone (Decadron) -- Used in treatment of various autoimmune disorders. By suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability, may decrease autoimmunity.
Adult Dose	10 mg IV q6h
Pediatric Dose	0.15 mg/kg IV q6h
Contraindications	Documented hypersensitivity; untreated active infection
Interactions	Barbiturates, phenytoin, and rifampin decrease effects; decreases effects of salicylates and vaccines used for immunization
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Increases risk of multiple complications, including severe infections; monitor adrenal insufficiency when tapering drug; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections are possible complications

FOLLOW-UP

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Further Inpatient Care:

• Patients with fulminant MS or acute disseminated encephalitis usually are admitted to neurologic ICU.

• Consider arranging for emergency plasmapheresis.

• Patients with MS exacerbations may be admitted (eg, neurology, medicine) or discharged, depending on presentation, confidence in diagnosis, and therapy.

Further Outpatient Care:

• Arrange for follow-up with neurology and/or ophthalmology in 1-2 days.

In/Out Patient Meds:

• As with any chronic condition, medication administration ideally is coordinated with primary care physician or others involved in the patient's long-term care.

• Spasticity

• Baclofen (Lioresal), in severe cases, intrathecally

• Tizanidine (Zanaflex)

• Diazepam (Valium)

• Clonazepam (Klonopin)

• Dantrolene (Dantrium)

• Trigeminal neuralgia - Carbamazepine (Tegretol)

• Intense tingling and burning sensations - May respond to antidepressant medication or may require narcotics

• Depression/fatigue

• Amantadine (Symmetrel)

Deterrence/Prevention:

• Consider postvoid residual urine volume test if a patient with known MS and no prior urinary assessment has UTI.

• If residual is greater than 100 mL, risk of recurrent UTIs is significant.

• Refer patient to urology and consult patient education/visiting nurse to instruct patient on self-catheterization.

Complications:

• Coma

• Delirium

• Emotional lability

• Nystagmus

• Optic nerve atrophy

• Paraplegia

• Sexual impotence in men

• UTIs

• Complications from chronic disability (eg, pneumonia, pulmonary embolism, infected decubiti)

Prognosis:

• Approximately 20-35% of patients with MS who have RR pattern experience complete or nearly complete recovery of acute exacerbation within 8 weeks, particularly when the exacerbation occurs early in disease course.

• About 90% of patients with ON experience complete recovery of visual acuity within 8-12 weeks. Even so, residual impairment of color vision and abnormal depth perception are common. Recurrence in either eye can be expected in 20-35% of ON patients.

Patient Education:

• Educate patients to always treat fevers aggressively with around-the-clock antipyretics.

• Support groups and organizations may be excellent patient resources.

• Discuss referral to research centers, especially for patients with more aggressive forms of MS.

• With patients on chronic therapy, confirm their familiarity with common adverse effects of interferon-beta-1B (Betaseron) and, to a lesser extent, interferon-beta-1A (Avonex).

• Flulike symptoms

• Pain and inflammation at the injection site

• Less frequently, abnormal liver function tests and severe (even suicidal) depression

• For patient education resources, visit eMedicine's Muscle Disorders Center. Also, see eMedicine's patient education article, Multiple Sclerosis.

MISCELLANEOUS

Section 9 of 12

Medical/Legal Pitfalls:

• Avoid the temptation to diagnose new MS in ED and/or counsel patients prior to diagnosis.

• Diagnosis of MS progression or new symptoms when another reversible lesion, such as mechanical spinal cord compression, might be causing new symptoms

• Advocates of medical marijuana believe that MS symptoms can be improved with consumption or use of cannabis. Evidence in the medical literature is anecdotal at present to support patients' subjective sense improvement in spasticity. No studies demonstrate an objective improvement in muscle tone.

Special Concerns:

• Pregnancy

• Symptoms of MS may stabilize or remit during pregnancy, but 20-40% of patients have relapse within 3 months after delivery.

• No evidence suggests that pregnancy affects long-term course of MS.

• Pediatric: MS is an unlikely diagnosis in those younger than 16 years.

• Geriatric: MS is an unlikely diagnosis in those older than 50 years.

• Be aware of the controversy surrounding long-term MS therapy with respect to cost-effectiveness, lack of outcomes research, and the impact on future clinical trials.

TEST QUESTIONS

Section 10 of 12

CME Question 1: Which of the following is not a known precipitant of multiple sclerosis (MS) exacerbations?

A: A bee sting
B: An asymptomatic urinary tract infection
C: A symptomatic urinary tract infection
D: Hyperthermia from any cause
E: Exercise

The correct answer is A: Hyperthermia is a well-documented precipitant of MS, as are infections independent of fever production. Urinary tract infections, whether symptomatic or asymptomatic, are important causes of exacerbations; emergency physicians also should look for infections of the respiratory system and decubiti. While most physical disabilities improve with exercise, MS patients often have a deleterious effect from it. Nonspecific activation of the immune system by bee venom, a popular alternative medical therapy for MS, is unproved clinically, but it has not been implicated in clinical deterioration. In fact, antigen-specific activation of the immune system is thought to explain the benefits of copolymer I, which together with beta-interferons represents an FDA-approved application of immunotherapy.

CME Question 2: Which of the following is not a likely initial presentation of multiple sclerosis (MS)?

A: Optic neuritis
B: Charcot triad (dysarthria, ataxia, tremors)
C: Acute total transverse myelitis
D: Paresthesias
E: Internuclear ophthalmoplegia

The correct answer is C: Almost all cases of acute transverse myelitis attributed to MS involve partial functional loss below the level of the lesion. Note that the inverse is not necessarily true, so patients who present with a partial deficit still require ED assessment to rule out a compressive lesion.

Pearl Question 1 (T/F): Multiple sclerosis (MS) is the most common cause of chronic disability among young adults.

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

Pearl Question 2 (T/F): The effects of pregnancy on multiple sclerosis (MS) are short term.

The correct answer is True: MS may stabilize or remit during pregnancy, but 20-40% of patients have a relapse within 3 months of delivery. No evidence indicates that pregnancy affects the long-term course of MS.

Pearl Question 3 (T/F): Multiple sclerosis (MS), in most cases, can be diagnosed easily in the ED.

The correct answer is False: MS is not diagnosed in the ED. Diagnosis is made by a neurologist who is familiar with the myriad presentations and radiographic, electrophysiologic, and cerebrospinal fluid (CSF) findings. Emergency evaluation of these patients focuses on identifying treatable conditions, particularly those that require prompt antimicrobial therapy or neurosurgical intervention.

Pearl Question 4 (T/F): The eye exam is invariably abnormal in multiple sclerosis (MS).

The correct answer is True: Look for abnormal pupillary response, uncoordinated eye movements, nystagmus, and/or loss of smooth finger pursuit.

PICTURES

Section 11 of 12

Caption: Picture 1. Multiple sclerosis. The spectrum of idiopathic inflammatory demyelinating diseases of the CNS.
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BIBLIOGRAPHY

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• Confavreux C, Hutchinson M, Hours MM, et al: Rate of pregnancy-related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group. N Engl J Med 1998 Jul 30; 339(5): 285-91[Medline].
• De Stefano N, Matthews PM, Fu L, et al: Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study. Brain 1998 Aug; 121 ( Pt 8): 1469-77[Medline].
• Edlich RF, Hammarskj M: Multiple sclerosis. In: Tintinalli JE, ed. Emergency Medicine. 4th ed. [CD-ROM]. McGraw-Hill; 1997:chap 197.
• Fazekas F, Deisenhammer F, Strasser-Fuchs S, et al: Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Austrian Immunoglobulin in Multiple Sclerosis Study Group. Lancet 1997 Mar 1; 349(9052): 589-93[Medline].
• Francis GS, Evans AC, Arnold DL: Neuroimaging in multiple sclerosis. Neurol Clin 1995 Feb; 13(1): 147-71[Medline].
• Johnson KP, Brooks BR, Cohen JA, et al: Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology 1995 Jul; 45(7): 1268-76[Medline].
• Kelley J, ed: Demyelinating diseases. In: Textbook of Internal Medicine. 3rd ed. [CD-ROM]. Lippincott-Raven; 1996:chap 437.
• Little N: Special neurologic problems: demyelinating disease. In: Rosen P, ed. Emergency Medicine. 3rd ed. [CD-ROM]. Mosby; 1992:chap 95.
• Lublin FD, Whitaker JN, Eidelman BH, et al: Management of patients receiving interferon beta-1b for multiple sclerosis: report of a consensus conference. Neurology 1996 Jan; 46(1): 12-8[Medline].
• Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG: Multiple sclerosis. N Engl J Med 2000 Sep 28; 343(13): 938-52[Medline].
• PRISMS Studfy Group: Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet 1998 Nov 7; 352(9139): 1498-504[Medline].
• Pryce G, Baker D: Emerging properties of cannabinoid medicines in management of multiple sclerosis. Trends Neurosci 2005 May; 28(5): 272-6[Medline].
• Rodriguez M, Karnes WE, Bartleson JD, et al: Plasmapheresis in acute episodes of fulminant CNS inflammatory demyelination. Neurology 1993 Jun; 43(6): 1100-4[Medline].
• Sellebjerg F, Frederiksen JL, Nielsen PM, Olesen J: Double-blind, randomized, placebo-controlled study of oral, high-dose methylprednisolone in attacks of MS. Neurology 1998 Aug; 51(2): 529-34[Medline].
• Thompson AJ, Polman CH, Miller DH, et al: Primary progressive multiple sclerosis. Brain 1997 Jun; 120 ( Pt 6): 1085-96[Medline].
• Trapp BD, Peterson J, Ransohoff RM, et al: Axonal transection in the lesions of multiple sclerosis. N Engl J Med 1998 Jan 29; 338(5): 278-85[Medline].
• Tullman MJ, Lublin FD: Combination therapy in multiple sclerosis. Curr Neurol Neurosci Rep 2005 May; 5(3): 245-8[Medline].
• Vastag B: Not so fast: research on infectious links to MS questioned. JAMA 2001 Jan 17; 285(3): 279-81[Medline].
• Weiner HL, Hohol MJ, Khoury SJ, et al: Therapy for multiple sclerosis. Neurol Clin 1995 Feb; 13(1): 173-96[Medline].
• Weinshenker BG: The natural history of multiple sclerosis. Neurol Clin 1995 Feb; 13(1): 119-46[Medline].

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