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| Multiple Sclerosis |
| Overview |
 | Onset
 | 20 to 35 year old in female |
| 35 to 45 year old in male |
| rare before 14 or after 60 year old |
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| 70 to 75% of patients are female |
| Prevalence: female:male 2:1, more common in white |
| Genetic: first degree relative 10-20X increased risk |
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| Schumacher Committee Criteria for MS Diagnosis |
| 1. Age at onset 10–50 years of age |
| 2. Neurological examination shows objective signs |
| 3. Neurological signs and symptoms implicate CNS white matter |
| 4. Dissemination in time established by either
| two attacks (lasting > or =24 hours, separated by < or = one month)
or |
| 6 months progression |
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| 5. Dissemination in space (two or more separate lesions) |
| 6. No better clinical explanation |
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McDonald committee for Diagnosis of MS
DIS=disseminated in space, DIT=disseminated in time |
| 1. Definite MS on clinical grounds:
| DIS: 2 or more lesions |
| DIT: 2 or more attacks |
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| 2. Localized disease
| DIS: 1 lesion, need
 | MRI to prove DIS, or |
| MRI finding and positive CSF finding; or |
| further clinical attack at a different location. |
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| 3. Multifocal single attack, need
| 2nd attack to confirm diagnosis |
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| 4. Single attack, single lesion
| DIS: Need MRI prove of DIS, plus |
| DIT: Need MRI or clinical proof of second attack |
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| 5. Primary progressive disease
| DIS: Need MRI, Evoked potential and CSF |
| DIT:
| MRI proof of DIT, or |
| progression for over one year |
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| Types |
| 85% start out as relapsing remitting.
| About 10% remains benign at 20 years |
| 55% RR-MS: Relapsing remitting MS - attacks occurring
average once per year |
| 30% SP-MS: Secondary Progressive MS |
| About 50% of RR-MS will become
SP-MS. |
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| 10-15% starts as progressive disease.
| 10% PP-MS: Primary progressive MS. Most commonly first develop symptom at age 40-60. |
| 5% PR-MS: Progressive relapsing |
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| MRI |
| Determining Abnormal MRI. Need 3 out of 4 of the following (Barkhof et al and Tintore et al):
| 1 Gd+ lesion or 9 T2 hyperintense lesions |
| 1 infratentorial lesion |
| 1 juxtacortical lesion |
| 3 periventricular lesion(1 spinal cord lesion = 1 brain lesion) |
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| MRI as a prognostic indicator in clinically isolated syndromes:
| MRI normal at presentation
| 5 years follow-up: 6% with clinically definite MS |
| 10 years follow-up: 10% with clinically definite MS |
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| MRI with 1.2 cc or greater T2 involvement
| 5 years follow-up: 96% with clinically definite MS |
| 10 years follow-up: 86% with clinically definite MS (some patients in the
5 year cohort not included in 10 year cohort) |
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| Other Tests |
| Every patient:
| Lab: ANA, B12, CBC, ESR |
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| On selected patient:
| MRI of spinal cord to rule out AVM, tumor, disc
| Also useful in older patients, age related lesions do not
occur in the spinal cord. |
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| Serology for collagen vascular disease |
| Serology for Lyme, Syphilis, HIV, HTLV-1 |
| Anti-neuronal Abs for paraneoplastic syndromes, especially for
patient with cerebellar symptoms. |
| ACE, chest x ray, pulmonary function for sarcoidosis. |
| VLCFA for adrenoleukodystrophy. |
| Evoked potential studies, see below |
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| CSF Studies |
| Strongly suggestive of MS
| Normal RBC and glucose |
| Normal or mildly elevated protein |
| 5-20 mononuclear cells/ul |
| Intrathecal IgG synthesis
| Increased IgG index or 24 hour synthesis rate |
| Increased free kappa light chains |
| Oligoclonal bands |
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| Discussion
| Cell count: RBC usually none. WBC: 1/3 has 5 to 50 lymphocytes |
| Protein: 1/4 of patients has mild elevation |
| Myelin basic protein:
| presence indicates demyelination |
| can be found in first 2 weeks after a substantial exacerbation in 50-90%
of patients |
| can be seen in other neuro disease, such as infarct, infection etc |
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| Immunoglobulin: IgG synthesis rate
| Indicates activity of Plasma cells |
| >3 in 80-90% of MS |
| elevated in 12% of normal individual, and 30-50% of CNS infections |
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| Immunoglobulin: IgG index
| >0.7 in 86-94% of MS |
| first CSF abnormality in early MS |
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| Oligoclonal bands
| present in over 90% of definite MS |
| seen in other inflammatory diseases |
| seen in 7% of normal control |
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| Evoked potential |
| % prolonged in |
possible MS |
probable MS |
definite MS |
| VEP |
40 |
60 |
85 |
| SSEP |
50 |
70 |
80 |
| BAEP |
30 |
40 |
70 |
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| Variants of MS |
| Balo's concentric sclerosis
| rare, affect young adults, more common in
Philippines & China, lasts a few months |
| concentric bands of intact myelin and
demyelinated zones |
| Respond to steroid |
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| Devic's disease (neuromyelitis optica)
| spinal cord and optic nerves affected. Brain is
spared |
| MRI brain normal. MRI spine striking lesions. |
| CSF: pleocytosis w neutrophil, elevated protein. |
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| Marburg's disease
| Acute form of MS |
| fulminant & progressive |
| Extensive myelin destruction with axonal loss and
edema |
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| Schilder's disease
| rare, affect children |
| visual problems or cortical blindness, |
| seizures, headache, vomiting |
| Large bilateral hemisphere demyelination |
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| Monophasic syndromes
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| Further reading |
| Return to Neuroland MS information center |
| Treatment: symptomatic treatment, disease modifying agents |
| Paty DW, Noseworthy JH, Ebers GC. Diagnosis of multiple sclerosis.
In: Paty DW, Ebers GC, eds. Multiple Sclerosis. Philadelphia: FA
Davis; 1998:48-134. |
| Schumacher GA, Beebe GW, Kibler RF et al. Problems of experimental
trials of therapy in multiple sclerosis: Report by the panel on the
evaluation of experimental trials of therapy in multiple sclerosis.
Ann NY Acad Sci 1965;122:552-568. |
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