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

Be aware of the relationship between Progressive Multifocal Leukoencephalopathy (PML) and patients who have received Natalizumab or Rituximab therapy.

Introduction

• PML is a JC Virus Encephalopathy commonly seen in immunocompromised patients.
• It is often associated with AIDS and other immunocompromised states.
• Oligodendrocytes, the CNS cells responsible for myelination, are preferentially infected by JC Virus (JCV).
• JC virus is a widespread human polyomavirus.

Aetiology

• The cause is attributed to JC virus, which is a common infection in the general population.
• Approximately 40-90% of people have been exposed to JC virus, usually asymptomatically, unless immunocompromised.
• The infection targets oligodendrocytes, leading to CNS demyelination.
• Associated with advanced cancers, bone marrow transplants, and severe immunosuppression (e.g., HIV with low CD4+ counts).

Drug Causes

• Natalizumab (Tysabri): Anti-α4 integrin
• Fingolimod (Gilenya): Sphingosine 1-phosphate receptor modulator
• Dimethyl fumarate (Tecfidera): Immunomodulator
• Rituximab: Anti-CD20
• Efalizumab: Anti-CD11a
• TNF Inhibitors: Adalimumab, Infliximab, Etanercept
• Ruxolitinib: JAK 1 and 2 inhibitor

Clinical Features

• Focal neurological signs vary by lesion site and size within white matter.
• Common symptoms include weakness, sensory loss, ataxia, brainstem signs, altered cognition, and visual disturbances.

Differential Diagnoses

• Multiple Sclerosis
• Susac Syndrome
• PML itself if presenting atypically

Differential Diagnoses in AIDS Patients

• Toxoplasmosis
• CNS Lymphoma
• AIDS Dementia Complex
• Cryptococcal Meningitis
• HIV Encephalopathy
• Cytomegalovirus (CMV) Infection
• Herpes Virus Infections

Investigations

• Blood Tests: FBC, U&E, CRP; HIV test, syphilis serology
• MRI Brain: Shows T2-weighted lesions in white matter, potentially involving the corpus callosum. May resemble glioma or lymphoma.
• CSF Analysis: Lumbar puncture with PCR for herpes viruses, JC virus, cell count, and protein.
• Brain Biopsy: May be required in ambiguous cases to confirm diagnosis.

Imaging

Management

• Diagnosis is based on clinical presentation, MRI, CSF changes, and serology.
• In HIV patients with low CD4 counts, initiate HAART (Highly Active Antiretroviral Therapy); however, 10-20% may experience immune reconstitution inflammatory syndrome (IRIS), which can lead to brain swelling and herniation.
• Cytosine Arabinoside (ara-C, Cytarabine): Administered intrathecally through a shunt in selected cases.
• Cidofovir: Initially showed promise for treating PML but lacks consistent efficacy data.
• Some patients with CD4 > 200 recover without additional treatment beyond antiretroviral therapy.
• Steroids may be considered, especially in cases with significant IRIS.

References

• Progressive Multifocal Leukoencephalopathy: New Concepts