Multiple sclerosis

• i. Most common demyelinating disease of the CNS; more common in North America, northern Europe, southeast Australia and New Zealand; causes focal demyelination of optic nerves, spinal cord and brain
• ii. Migration before age 15 from a high to low incidence area reduces the likelihood of developing MS while migration before age 15 from a low to high incidence increases the risk for developing MS; migration after age 19 does not affect the risk
• iii. Risk of developing MS is increased 15-20 fold in first degree relatives of MS patients with a higher concordance rate of monozygotic twins than dizygotic twins
• iv. Associated particularly with HLA-DR2
• v. Symptoms: commonly presents with weakness (proximal and distal), paresthesia, and sensory loss of one or more limbs; also commonly presents with optical findings; is often relapsing and remitting but can be progressive; loss of reflexes is common
• vi. Plaques of MS are often located in the white matter at the junction between the cerebral gray and white matter or cerebellar white matter and peduncles or adjacent to the lateral ventricles
• vii. Microscopically see sheets of foamy (lipid droplets) macrophages (which exhibit major histocompatibility complex class II antigens) toward the margin of an active plaque; may also see lymphocytic inflammation in regions of active demyelination
  • 1. inactive plaques have obvious loss of oligodendrocytes with most of the cells in the plaque being astrocytes
• viii. neuromyelitis optica (Devic’s disease – a variant of MS)
  • 1. characterized by development of optic neuritis and acute transverse myelitis within weeks of each other; most go on to develop other manifestations of MS
• ix. Usually associated with oligoclonal bands of immunoglobulins on electrophoresis of the CSF (IgG bands are present in about 90% of MS patients and is considered the most reliable test for diagnosing MS) (bands also occur in syphilis and subacute sclerosing panencephalitis); Remember: syphilis and sclerosis are ‘band’ groupies
  • 1. proportion of IgG is increased in about 2/3rds of MS patients
    • a. formula: CSF IgG/serum IgG  CSF albumin/serum albumin; a ratio of more than 1.7 indicates a high probability of MS
  • 2. 1/3rd of MS patients have a slight to moderate mononuclear pleocytosis (a measure of the activity of the disease); IgM is most commonly associated with a polyradiculopathy
  • 3. 40% of MS patients have an increased protein count in the CSF
  • 4. high concentration of myelin basic protein (MBP) is present in acute exacerbations of MS
  • 5. slight to moderate pleocytosis may also be present
• x. More than 85% of MS patients have periventricular lesions (Dawson’s finger) that are oriented perpendicularly to the long axis of the brain and lateral ventricles; next most common site is the corpus callosum where 50-90% of patients have such lesions
• xi. CT: lesions are usually iso or hypodense with brain; enhancement following contrast administration is variable with some enhancing and some not; some have a ring-like contrast enhancement
• xii. MRI is 85% sensitive in detecting MS plaques; most of the plaques are clinically silent; most lesions are iso or hypointense on T1 scans and hyperintense on T2 scans; diagnostic criteria for MS: 3 or more lesion of 5 mm or greater in size with clinical correlation; enhancement following contrast administration represents blood brain barrier disruption and is usually only seen during the active demyelinating stage but does occur and makes the lesion look like a low grade glioma in some cases
• xiii. EMG and nerve conduction
  • 1. MS is a demyelinating neuropathy and thus has decreased conduction velocities (compared to axonal neuropathies that have normal conduction velocities), distal latencies and F wave latencies
• xiv. MS patients are evaluated with the Kurtzke scale which reflects the ability to care for acitivities of daily living