What are the symptoms of Progressive Multifocal Leukoencephalopathy (PML)?

Symptoms of Progressive Multifocal Leukoencephalopathy (PML)

PML presents with subacute, progressive neurological symptoms developing over weeks, most commonly including aphasia, behavioral and cognitive changes, visual field deficits, hemiparesis, and seizures. 1

Core Clinical Features

Temporal Pattern

• Subacute onset with symptoms evolving over weeks (not hours to days) 1
• Progressive course without spontaneous stabilization or resolution 1
• Continuous worsening distinguishes PML from relapsing-remitting conditions like MS 1

Primary Neurological Manifestations

Cognitive and Behavioral Symptoms:

• Behavioral alterations and personality changes 1
• Neuropsychological dysfunction including confusion 1
• Memory impairment 2
• Altered mental status 3

Motor Deficits:

• Hemiparesis (weakness on one side of the body) 1, 4
• Progressive motor impairment 3
• Difficulty walking 1

Speech and Language:

• Aphasia (language dysfunction) 1, 4
• Dysarthria (difficulty speaking) 3
• Difficulty talking 1

Visual Disturbances:

• Retrochiasmal visual deficits (visual field cuts) 1, 4
• Vision problems 1
• Visual impairments 3

Other Neurological Features:

• Seizures 1, 4, 3
• Dizziness or loss of balance 1

Atypical Presentations

Less Common Symptoms (that may suggest alternative diagnoses):

• Fever is not typical of PML and suggests concurrent infection or immune reconstitution inflammatory syndrome 3
• Diplopia, paresthesia, paraparesis, optic neuritis, and myelopathy are more characteristic of MS than PML 1, 4

Critical Clinical Context

Risk Factors and Patient Population:

• PML occurs almost exclusively in immunocompromised patients 1, 4
• Most common in HIV/AIDS patients with CD4 or CD8 immunosuppression 1, 4
• Associated with immunomodulatory therapies (natalizumab, rituximab) 1, 5
• Seen in hematologic malignancies, organ transplant recipients, and rheumatic disease patients 4, 2

Prognosis:

• Usually fatal without treatment 1
• 3-month mortality rate of 20-50% 6
• High mortality risk necessitates prompt diagnosis 3

Key Diagnostic Pitfalls

Common Misdiagnosis Scenarios:

• PML vs MS differentiation is critical in natalizumab-treated patients, as symptoms can overlap but temporal patterns differ (subacute progressive vs acute relapsing) 1, 7
• Atypical presentations with fever and seizures can complicate diagnosis and suggest disease complexity 3
• Early disease may present with non-specific symptoms like isolated memory disturbance, delaying diagnosis 2
• Any new neurological symptoms beyond 18 months of natalizumab therapy should raise suspicion for PML 8, 4