Symptoms of Progressive Multifocal Leukoencephalopathy (PML)
PML presents with subacute, progressive neurological symptoms developing over weeks, most characteristically including aphasia, behavioral and neuropsychological alterations, retrochiasmal visual deficits, hemiparesis, and seizures. 1, 2
Clinical Onset and Evolution
- Subacute onset is the hallmark, with symptoms evolving progressively over weeks rather than the acute onset (hours to days) seen in multiple sclerosis 1
- Symptoms are continuously progressive without the spontaneous stabilization or resolution that occurs in MS relapses 1
- The progressive nature distinguishes PML from other demyelinating conditions that typically stabilize even without treatment 1
Core Neurological Symptoms
The characteristic symptom constellation includes:
- Aphasia (language impairment) 1, 2
- Behavioral and neuropsychological alterations (personality changes, cognitive decline) 1, 2
- Retrochiasmal visual deficits (visual field cuts, cortical blindness) 1, 2
- Hemiparesis (unilateral weakness) 1, 2
- Seizures 1, 2
Additional Neurological Manifestations
- Movement impairment and motor deficits 3
- Cognitive disability beyond behavioral changes 3
- Dysarthria (speech difficulties) 3
- Visual impairments beyond retrochiasmal deficits 3
Important Clinical Distinctions
PML rarely presents with symptoms typical of MS, which helps differentiate the two conditions 2:
- Diplopia (double vision) is uncommon in PML 1, 2
- Paresthesias (sensory symptoms) are rare 1, 2
- Paraparesis is atypical 1, 2
- Optic neuritis does not occur 1, 2
- Myelopathy (spinal cord involvement) is rare 1, 2
Atypical Presentations
While less common, some patients may present with:
- Fever (though not typically associated with PML, suggests diagnostic complexity) 3
- Altered behavior as the primary presenting feature 3
- Widespread tonic-clonic seizures at presentation 3
Critical Clinical Pitfalls
- Do not dismiss PML based on a single negative CSF JCV PCR test, as viral loads may be below detection threshold in early disease 2
- In patients on natalizumab beyond 18 months, any new neurological symptoms warrant high suspicion for PML 2, 4
- The absence of fever or seizures does not exclude PML, though their presence may indicate a more complex or aggressive course 3
- Symptoms progress continuously without spontaneous improvement, unlike MS relapses that typically stabilize 1