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Published on January 4, 2008

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Multiple Sclerosis: Making the Diagnosis:  Multiple Sclerosis: Making the Diagnosis M. Wallin, MD, MPH Neurology Service VAMC, Washington, DC Multiple Sclerosis: Making the Diagnosis Topical Outline:  Multiple Sclerosis: Making the Diagnosis Topical Outline MS Background & Diagnostic Approach Diagnostic Criteria & Evaluation MS Variants Differential Diagnosis Clinical Cases Definition of Multiple Sclerosis:  Definition of Multiple Sclerosis An inflammatory demyelinating disease of the CNS where there is: Dissemination in space Dissemination in time No alternative neurologic disease MS is a clinical diagnosis Multiple Sclerosis Epidemiology (Wallin M, et al Baker Clin Neurol CD-2003):  Multiple Sclerosis Epidemiology (Wallin M, et al Baker Clin Neurol CD-2003) The most common progressive neurologic disease of young adults Affects 350,000 persons in the USA Risk Factors: Female sex White race Northern latitude (USA) High socioeconomic status Scandinavian ancestry Approach to the Diagnosis of MS (Modified from Fleming J, MS & Its Masquerades, AAN-2003):  Approach to the Diagnosis of MS (Modified from Fleming J, MS & Its Masquerades, AAN-2003) Treat for MS Close follow-up &/or Focused work-up Reassure & evaluate when appropriate Multiple Sclerosis Subtypes (Lublin F, et al Neurology 1996):  Multiple Sclerosis Subtypes (Lublin F, et al Neurology 1996) Asymptomatic Symptomatic Relapsing-remitting (85% at onset) Primary progressive (10%) Secondary Progressive (transitional form) Progressive Relapsing (5%) Multiple Sclerosis Subtypes (Coyle P, CNS News 2002; adapted from Lublin F, et al Neurology 1996):  Multiple Sclerosis Subtypes (Coyle P, CNS News 2002; adapted from Lublin F, et al Neurology 1996) Onset symptoms of MS (Weinshenker B, et al Brain, 1989):  Onset symptoms of MS (Weinshenker B, et al Brain, 1989) Clinical Features Suggestive of MS:  Clinical Features Suggestive of MS Onset between 15-50 years Blurred or double vision Lhermitte’s sign Fatigue Heat sensitivity Bladder symptoms Cognitive or affective changes MS Disease Timeline (Fox RJ, Sweeny PJ, Cleveland Clinic, May 2002):  MS Disease Timeline (Fox RJ, Sweeny PJ, Cleveland Clinic, May 2002) Schumacher Diagnostic Criteria (Schumacher G, et al. Ann NY Acad Sci 1965):  Schumacher Diagnostic Criteria (Schumacher G, et al. Ann NY Acad Sci 1965) The following 6 criteria are essential for a diagnosis of “definite MS”: Age between 10-50 yrs Objective abnormalities on exam Two or more separate lesions in the CNS CNS disease must reflect white matter involvement Consistent time course Attacks last > 24 hrs; spaced 1 mo apart Slow/stepwise progression > 6 mo No better explanation by a physician competent in clinical neurology Poser Diagnostic Criteria (Poser C, et al Ann Neurol, 1983) :  Poser Diagnostic Criteria (Poser C, et al Ann Neurol, 1983) McDonald Diagnostic Criteria Primary Progressive MS :  McDonald Diagnostic Criteria Primary Progressive MS Insidious course with steady progression of clinical deficits with paraclinical evidence: DIS by MRI in combination with VER & positive CSF DIT by MRI or continued progression for 1 yr McDonald Diagnostic Criteria MRI-High Specificity & Sensitivity for MS:  McDonald Diagnostic Criteria MRI-High Specificity & Sensitivity for MS Typical MS demyelinating lesions meeting at least 3 of the following 4 criteria: At least 1 Gd lesion or at least 9 T2 lesions At least one infratentorial lesion At least one juxtacortical lesion At least 3 periventricular lesions McDonald Diagnostic Criteria MRI-Dissemination in Space:  McDonald Diagnostic Criteria MRI-Dissemination in Space Stringent MRI Criteria At least 3 of the 4 criteria must be met: 1 Gd enhancing lesion or 9 T2 lesions > 1 Infratentarial lesion > 1 Juxtacortical lesion > 3 Periventricular lesions MRI + CSF Criteria Both of the following must be met: > 2 lesions consistent with MS CSF showing OCB or increased IgG index McDonald Diagnostic Criteria MRI-Dissemination in Time:  McDonald Diagnostic Criteria MRI-Dissemination in Time If the first MRI is performed 3 months after the clinical event, 1 of the 2 below must be found: > 1 Gd lesion not at site of original attack; or MRI 3 months later showing a new T2 or Gd lesion If the first MRI is performed < 3 months after the clinical event, then a second MRI done 3 months after the attack provides evidence for DIT if 1 of the 2 below must be found: New Gd lesion on the second MRI Later MRI showing new T2 or Gd lesion McDonald Diagnostic Criteria Correct Application:  McDonald Diagnostic Criteria Correct Application Clinical & lab findings typical of MS No better explanation of patient’s findings Unusual cases require close follow-up Criteria may be applied flexibly but not casually Revisions to criteria may be needed in future McDonald Diagnostic Criteria Prospective Performance (Dalton, et al Ann Neurol 2002):  McDonald Diagnostic Criteria Prospective Performance (Dalton, et al Ann Neurol 2002) Diagnosis of MS by McDonald Diagnostic Criteria in CIS patients at one year after presentation compared to reanalysis of these patients by Poser criteria at three years: Sensitivity: 83% Specificity: 83% PPV: 75% NPV: 89% Focused Neurologic Exam (Adapted from Whitney D, Int J MS Care, 2001):  Focused Neurologic Exam (Adapted from Whitney D, Int J MS Care, 2001) MSt: Attention, psychomotor slowing CN: VA, fundoscopic exam, VFs, swinging flashlight, EOM evaluating for paresis (INO) & nystagmus Reflexes: asymmetries, Babinski sign Motor: spasticity, pyramidal pattern of weakness Sensory: Thoracic or cervical level Gait: integrates many functions, 25’ timed walk Bladder: PVR (if symptomatic) Imaging & Lab Work-up for MS (Modified from Fleming J, MS & Its Masquerades, AAN-2003):  Imaging & Lab Work-up for MS (Modified from Fleming J, MS & Its Masquerades, AAN-2003) Brain MRI with Gd VERs CBC, Chem 7, Liver enz, UA Lyme serology (based on exposure history) ANA, RPR, ESR B12 TSH HIV CSF (based on clinical and MRI) C & T Spine MRI (if Brain MRI nl or indicated clinically) CXR MRI: FLAIR & T1 with Gadolinium (Noseworthy J, et al NEJM, 2000):  MRI: FLAIR & T1 with Gadolinium (Noseworthy J, et al NEJM, 2000) MRI: T1 “Black Holes”:  MRI: T1 “Black Holes” MRI: Sagittal Views:  MRI: Sagittal Views MRI: Spinal Imaging:  MRI: Spinal Imaging Visual Evoked Potentials (Baker’s Clin Neurol 2003):  Visual Evoked Potentials (Baker’s Clin Neurol 2003) Oligoclonal Bands:  Oligoclonal Bands Baker's Clinical Neurology, CDROM-2003 MS Variants:  MS Variants Marburg variant Balo’s Concentric Sclerosis Schilder’s Disease Disseminated subpial demyelination Mass Lesion Other Disorders:  Other Disorders Neuromyelitis Optica (Devic Syndrome) Relapsing (55%), monophasic (35%) MRI: cord lesions, chiasmal signal changes CSF: generally >100 wbc,  protein, rare OCB Postinfectious encephalomyelitis or ADEM Monophasic with preceeding event common (70%) Most common in children Altered LOC and seizures common MRI: bilateral symmetric lesions Clinically Isolated Syndromes:  Clinically Isolated Syndromes Optic Neuritis Risk factors for MS (60-75%) History of minor neurologic sxs Unilateral optic neuritis Brain MRI lesions Abnormal CSF Abormal VERs Clinically Isolated Syndromes :  Clinically Isolated Syndromes Transverse Myelitis Risk factors for MS Incomplete transverse myelitis Asymmetric motor or sensory findings Brain MRI lesions Abnormal CSF Abnormal VER and SSEPs Others (Brainstem, Cerebellum) Differntial Diagnosis in MS (Frohman E, et al Neurology, 2003):  Differntial Diagnosis in MS (Frohman E, et al Neurology, 2003) Red Flags for Misdiagnosing MS :  Red Flags for Misdiagnosing MS MRI changes without clinical correlate Known psychiatric disease Normal neurologic examination Atypical clinical features Disease onset at the extremes of age Extraneural systemic disease Prominent gray matter symptoms Case #1:  Case #1 31 year old Asian female presents with subacute onset of right sided trunk numbness (T4 level) and asymmetric leg weakness. No prior neurologic symptoms or signs. MRI of cord shows patchy upper thoracic T2- signal lesion. CSF: 100 wbc, increased protein & negative OCBs. Case #2:  Case #2 18 year old male high school senior presents with 48 hours of blurred vision, bilateral leg weakness with right arm ataxia. He appears to be alert but is a bit slow to respond to questions. No recent illnesses or significant PMH. MRI shows bilateral brainstem, occipital and cerebellar T2-lesions some of which enhance. His family is extremely concerned and ask your opinion on his diagnosis and prognosis. Breaking the news of an MS diagnosis:  Breaking the news of an MS diagnosis Communicate with the patient face-to-face Explain prognosis and treatment using lay terms Give hope to the patient by: encouraging pursuit of personal/career goals Correcting pessimistic impressions of MS Provide information on future follow-up and patient support resources MS Patient Information:  MS Patient Information National MS Society www.nmss.org Consortium of MS Centers www.mscare.org Multiple Sclerosis Association of America www.msaa.com Paralyzed Veterans of America www.pva.org VA MS Centers of Excellence (East & West) www.va.gov/ms

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