Makindo Medical Notes

Related Subjects: |Neurological History taking |Motor Neuron Disease (MND-ALS) |Miller-Fisher syndrome |Guillain Barre Syndrome |Multifocal Motor Neuropathy with Conduction block |Multiple Sclerosis (MS) Demyelination |Transverse myelitis |Acute Disseminated Encephalomyelitis |Progressive Multifocal Leukoencephalopathy (PML) |Inclusion Body Myositis |Cervical spondylosis |Anterior Spinal Cord syndrome |Central Spinal Cord syndrome |Brown-Sequard Spinal Cord syndrome |Spinal Cord Compression |Spinal Cord Haematoma |Spinal Cord Infarction

🧠 Progressive Multifocal Leukoencephalopathy (PML) is a rare but devastating JC virus encephalopathy seen in immunocompromised patients. ⚠️ Always consider it in patients who have received Natalizumab or Rituximab therapy.

🔎 Introduction

• PML is caused by reactivation of the JC Virus (a human polyomavirus).
• Commonly associated with AIDS, advanced cancers, bone marrow transplantation, and immunosuppressive drugs.
• JC virus infects oligodendrocytes → causes patchy CNS demyelination.
• Most people (40–90%) carry latent JC virus asymptomatically, but reactivation occurs in immunosuppression.

⚠️ Aetiology

• JC Virus infection targeting oligodendrocytes → progressive demyelination.
• Triggered by:
  • Severe immunosuppression (e.g., HIV with CD4 < 200).
  • Immunosuppressive therapies: monoclonal antibodies, chemotherapy, steroids.

💊 Drug-Associated Causes

• Natalizumab (anti-α4 integrin, MS & Crohn’s).
• Rituximab (anti-CD20, haematological malignancies, autoimmune disease).
• Fingolimod (MS, sphingosine-1P modulator).
• Dimethyl fumarate (MS immunomodulator).
• Efalizumab (anti-CD11a).
• TNF inhibitors (adalimumab, infliximab, etanercept).
• Ruxolitinib (JAK 1/2 inhibitor).

🩺 Clinical Features

• Highly variable, depends on white matter lesion sites:
• ⚡ Focal weakness or sensory loss
• 🎯 Ataxia, brainstem signs
• 🧩 Cognitive impairment, confusion
• 👀 Visual disturbances
• Seizures can occur

🔍 Differential Diagnoses

• Multiple Sclerosis
• Susac Syndrome
• Glioma / CNS lymphoma
• In AIDS patients:
  • Toxoplasmosis
  • CNS Lymphoma
  • Cryptococcal meningitis
  • HIV encephalopathy
  • CMV or HSV infection

🧪 Investigations

• Bloods: FBC, U&E, CRP; HIV serology, syphilis screen.
• MRI Brain: T2 hyperintense white matter lesions, often asymmetrical, involving parietal-occipital lobes, corpus callosum. May mimic MS or tumour.
• CSF: PCR for JC virus (diagnostic gold standard).
• Brain Biopsy: Rare but definitive when imaging/CSF inconclusive.

🖼️ Imaging

💊 Management

• HIV Patients: Start/optimise HAART → some recover if CD4 >200.
• IRIS (immune reconstitution inflammatory syndrome): Seen in 10–20% post-HAART, may worsen oedema. Steroids sometimes used.
• Drug-induced PML: Stop causative drug (e.g., Natalizumab, Rituximab).
• Antivirals / chemotherapy: Limited evidence for agents like Cidofovir or Cytarabine (ara-C).
• Supportive Care: Seizure control, neurorehab, ICP monitoring.

📉 Prognosis

• Without treatment: median survival ~6 months.
• With HAART: some long-term survival possible.
• Drug-associated PML: prognosis varies, depends on immune recovery after drug withdrawal.

📚 References

• Progressive Multifocal Leukoencephalopathy: New Concepts
• Clifford DB, et al. Neurology. 2010 – Natalizumab-associated PML risk factors.
• D'Souza A, et al. Lancet Neurology. 2019 – PML in immunotherapy.