Progressive multifocal leukoencephalopathy

Background

• Progressive multifocal leukoencephalopathy (PML) is a rare, demyelinating CNS disorder
• Associated with reactivated JC virus
• Seen almost exclusively in immunosuppressed patients, usually due to:
  • AIDS
  • Leukemia, lymphoma, myeloproliferative disorders (with or without chemo)
  • Post solid organ or stem cell transplant
  • Autoimmune disorders (with or without immune-modulating medications)
  • Medications: Natalizumab, rituximab, infliximab, mycophenolate mofetil

Clinical Features

• Altered mental status
• Aphasia
• Ataxia
• Hemiparesis
• Hemiplegia and visual field disturbances
• Seizure
• Cranial nerve palsies (rare)
• Cervical spine involvement (rare)

Differential Diagnosis

Altered mental status

Diffuse brain dysfunction

• Hypoxic encephalopathy
• Acute toxic-metabolic encephalopathy (Delirium)
  • Hypoglycemia
  • Hyperosmolar state (e.g., hyperglycemia)
  • Electrolyte Abnormalities (hypernatremia or hyponatremia, hypercalcemia)
  • Organ system failure
  • Hepatic Encephalopathy
  • Uremia/Renal Failure
  • Endocrine (Addison's disease, Cushing syndrome, hypothyroidism, myxedema coma, thyroid storm)
  • Hypoxia
  • CO2 narcosis
• Hypertensive Encephalopathy
• Toxins
• TTP / Thrombotic thrombocytopenic purpura
• Alcohol withdrawal
• Drug reactions (NMS, Serotonin Syndrome)
• Environmental causes
  • Hypothermia
  • Hyperthermia
• Deficiency state
  • Wernicke encephalopathy
  • Subacute Combined Degeneration of Spinal Cord (B12 deficiency)
  • Vitamin D Deficiency
  • Zinc Deficiency
• Sepsis
• Osmotic demyelination syndrome (central pontine myelinolysis)
• Limbic encephalitis

Primary CNS disease or trauma

• Direct CNS trauma
  • Diffuse axonal injury
  • Subdural/epidural hematoma
• Vascular disease
  • Intraparenchymal hemorrhage
• SAH
• Stroke
  • Hemispheric, brainstem
• CNS infections
  • Encephalitis
  • Anti-NMDA receptor encephalitis
  • Meningitis
• Neoplasms
  • Paraneoplastic Limbic encephalitis
  • Malignant Meningitis
  • Pancreatic Insulinoma
• Seizures
  • Nonconvulsive status epilepticus
  • Postictal state
• Dementia
  • Alzheimer's
  • Lewy Body Dementia
  • Frontotemporal Dementia

Psychiatric

• Acute psychosis
• Catatonia
• Excited delirium
• Malingering
• Steroid induced psychosis

Evaluation

• Evaluate for other (especially easily treatable) causes of symptoms
• MRI brain: non-enhancing, multifocal areas of white matter demyelination
• PCR for JC virus (CSF, blood, urine)

Management

• Limit duration of immunosuppression
  • HIV/AIDS patients, antiretroviral therapy is key
• Cidofovir may be useful in non-AIDS patients