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Updated: Sep 25 2021

Diseases of Myelination

  • Snapshot
    • A 32-year-old man presents to the emergency department with worsening lower extremity weakness. The patient was in his usual state of health until approximately one week prior to presentation, where he developed increased difficulty climbing the stairs. Now he is unable to stand. A few weeks ago he developed bloody diarrhea, which he attributes to drinking unpasteurized milk. On physcal examination, he has bilateral lower extremity 1/5 strength with absent patellar reflexes. (Guillain-Barre syndrome)
  • Guillain-Barré Syndrome
    • Introduction
      • acute inflammatory demyelinating polyradiculopathy (AIDP)
        • most common presentation
        • decreased axonal conduction speed
      • inflammatory demyelination of peripheral nerves
      • autoimmune attack of peripheral Schwann cells due to molecular mimicry
        • previous Campylobacter jejuni and Mycoplasma pneumoniae
          • may have an association with Zika virus infection
    • Presentation
      • symptoms
        • symmetric weakness usually begins in distal limbs and moves proximally
          • can begin proximally or a combination of proximally and distally
      • physical exam
        • decreased or absent deep tendon reflexes
        • cranial nerve involvement common resulting in facial paralysis
        • autonomic dysfunction resulting in cardiac irregularities and fluctuations in blood pressure
    • Evaluation
      • LP
        • albuminocytologic dissociation
          • ↑ CSF protein with normal cell count
    • Treatment
      • almost all patients survive and achieve complete recovery in several weeks
      • respiratory support is critical until recovery
        • pulmonary function testing
      • plasmapheresis or IV immunoglobulin
        • equal efficacy; no additive benefit
    • Prognosis, prevention, and complications
      • prognosis
        • low mortality
      • complications
        • respiratory failure
  • Progressive Multifocal Leukoencephalopathy (PML)
    • Introduction
      • widespread CNS demyelination due to destruction of oligodendrocytes
      • associations
        • latent JC virus reactivation
        • ↑ risk with natalizumab
        • ↑ risk with rituximab
      • seen in the immunosuppressed
        • HIV infection
          • < 200 per mm3
        • organ transplant patients
    • Presentation
      • subacute neurological deficits
        • e.g., hemiparesis, monoparesis, ataxia, altered mental status
    • Evaluation
      • clinical diagnosis with MRI imaging
        • MRI
          • symmetric or asymmetric lesions in multifocal areas
      • PCR of CSF for JC virus
      • brain biopsy
    • Treatment
      • patients with HIV
        • antiretroviral therapy
      • natalizumab-associated
        • stop agent
        • initiate plasma exchange
    • Prognosis, prevention, and complications
      • prognosis
        • HAART therapy improves survival in patients with HIV
      • prevention
        • improving CD4+ count in patients with HIV
      • complications
        • death
  • Acute Disseminated (Postinfectious) Encephalomyelitis
    • Introduction
      • autoimmune inflammatory demyelination of the CNS secondary to infection or vaccination
        • via infection
          • e.g., chickenpox and measles
        • via vaccinations
          • e.g., rabies and smallpox
    • Presentation
      • symptoms
        • acute and rapidly progressive development
          • multifocal neurological deficits
            • altered mental status
            • motor deficits
            • cranial nerve neuropathy
            • ataxia
            • sensory deficit
    • Evaluation
      • clinical diagnosis
    • Treatment
      • high-dose corticosteroids
        • IVIG or plasma exchange if poor response
      • acyclovir
    • Prognosis, prevention, and complications
      • prevention
        • no small pox vaccine before 12 months of age
      • complications
        • neurologic impairment
  • Metachromic Leukodystrophy
    • Introduction
      • autosomal recessive lysosomal storage disease due to deficient arylsulfatase A
      • inability to degrade sulfatides → sulfatide build up → myelin breakdown
    • Presentation
      • symptoms
        • diverse neurological impairment depending on subtype
          • e.g., motor skill regression in late infantile subtype
    • Evaluation
      • arylsulfatase enzyme activity in leukocytes
        • decreased
      • biopsy
        • neural tissue metachromatic lipid deposits
    • Treatment
      • no curative treatment
  • Charcot-Marie-Tooth Disease
    • Introduction
      • also known as hereditary motor and sensory neuropathy (HMSN)
      • group of disorders negatively affecting peripheral nerves and/or myelin
        • genetically distinct disorders
    • Presentation
      • symptoms
        • peroneal nerve neuropathy
          • lower leg atrophy
            • "inverted bottle" appearance
        • diminished or absent reflexes
        • decrease vibration and proprioception sense
        • pes cavus
    • Treatment
      • supportive
  • Central Pontine Myelinolysis (CPM)
    • Introduction
      • pontine demylination
        • loss of corticospinal and corticobulbar tracts
          • due to rapid correction of hyponatremia
          • can result in "locked-in syndrome"
    • Presentation
      • symptoms
        • pseudobulbar palsy with spastic quadriparesis
          • locked-in like presentation
            • can move eyes and blink
        • may also include cognitive function changes
    • Prognosis
      • often fatal
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