12.11.05 Clinic notes

MS

• • Course not thought to be related to relapse rate

  • EBV

    • Prevalence 90% in healthy population

    • Prevalence 100% in MS population

    • Mimicry?

  • 2 disease processes?

    • Inflammation

    • Neurodegeneration

  • Relapse rate 0.6-0.8 episodes per year

  • Subtype

    • RRMS

      • 85% of cases

      • No progression between relapses

    • PPMS

      • 10% of cases

      • No relapses

      • Continuous progression

    • PRMS

      • Clearly defined relapses

      • Disease progression between relapses

    • SPMS

      • Initial diagnosis is RRMS

      • But then continuous disease progression

  • DMT

    • IFNb

      • Blocks T-cell proliferation and tumor necrosis factor production

      • 3 different types

    • Glatiramer acetate

      • Immunomodulator

      • Inhibits T-cell activity

    • Mitoxantrone

    • Inhibits T-cell, B-cell, and macrophage proliferation

    • Decreases the secretion of pro-inflammatory cytokines and increases an anti-inflammatory response via promotion of the T-cell suppressor function

    • Inhibits macrophage-mediated myelin degradation

    • Natalizumab

      • Anti-alpha4-integrin

      • Inhibits the adhesion of leukocytes to their counter-receptor

    • Prevents cells crossing BBB

    • Fingolimod

      • First oral disease modifying drug

      • Sphingosine 1-phosphate receptor modulator

      • Sequesters lymphocytes in lymph nodes

Synamet

• • Combination of carbidopa and levodopa

  • Carbidopa is polar and so cannot cross the blood brain barrier

    • But prevents peripheral conversion of levodopa to dopamine

    • Thereby reduces the unwanted peripheral side effects of levodopa

      • Nausea + vomiting

    • Also increases the quantity of levodopa in the bloodstream that is available to enter the brain

Entacapone

• • Catechol-O-methyl transferase (COMT) inhibitor

  • Prevents COMT from metabolizing L-DOPA into 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the periphery, which does not easily cross the blood brain barrier (BBB)

  • May cause urine to turn reddish-brown

Stalevo

• • Anti-parkinsonian dopaminergic combination medication

  • Contains carbidopa, levodopa, and entacapone

Myotonic dystrophy

• • Army drink-drive guy

  • Chronic, slowly progressing, highly variable, inherited multisystemic disease

  • Trinucleotide expansion

  • Characterized by muscular dystrophy, cataracts, heart conduction defects, endocrine changes, and myotonia

  • Two types:

    • DM1, also called Steinert disease

      • Has a severe congenital form and a milder childhood-onset form

    • DM2, also called proximal myotonic myopathy (PROMM) or adult-onset form

      • Rarer than DM1 and generally manifests with milder signs and symptoms

  • Autosomal dominant inheritance

  • Presentation

    • Muscle wasting

    • Slow relaxation

    • Thenar tap test

    • Frontal hair loss

    • Hyporeflexia

    • Sunken face

  • A useful clinical clue for diagnosis is the failure of spontaneous letting go of the hands following strong handshakes due to myotonia

Notes

• • Leprosy is the most common global cause of neuritis

  • Sarcoidosis can have neurological manifestations

    • Neurologic findings are observed in about 5% of patients

    • Known as neurosarcoidosis

    • Cranial nerves are predominantly affected

      • Peripheral facial nerve palsy, often bilateral, is the most common neurological manifestation

  • Sildenafil-associated anterior ischemic optic neuropathy