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Progressive Multifocal Leukoencephalopathy (PML)

posted Aug 9, 2013, 6:50 PM by Purnema Madahar   [ updated Aug 9, 2013, 6:59 PM ]

Today's Monte Minute is brought to you by our 'Resident as Teacher' rotator, Matt Liakos.

On Thursday, we heard a case about a 54 M with AIDS and a low CD4 count presenting with 4 weeks of feeling “off-balance”.  He felt as if he was tripping over himself when walking and unsteady on his feet.  The symptoms started 4 weeks prior to presentation, was subtle at first but progressive.  He also complained of blurry vision over this time period, general weakness and difficulty opening jars in the house.  He denied fever, headache.  Physical exam showed normal mental status, no meningeal sings, dysmetria in the left arm, weakness in the right leg and a left upper quadrant homonymous quadrantanopia.

There were a few common diagnoses at the top of everyone’s lists: PML, toxoplasmosis and CNS lymphoma. 

Toxoplasmosis represents the most common neurologic infection in AIDS patients.  The main presenting symptoms for toxoplasmosis include altered mental status (75%), fever (10-72%), seizures (33%), headache (56%), focal neuro deficits (60%).  Patients often fit the picture of encephalopathy, meningoencephalitis.  In primary CNS lymphoma associated with AIDS, again, patients manifest symptoms of increased intracranial pressure, and seizures in addition to focal neurologic findings.   A good way to break this down is by diseases that present with mass effect and thus increased ICP (headache, nausea, vomiting, confusion, lethargy)  and those that do not.  The first group includes Toxo, CNS lymphoma and much less commonly brain abscesses, cryptococcomas, syphilitic gummas.  The latter includes PML, HIV encephalopathy, CMV encephalitis.  So, out of the three diagnoses on our differential, toxo and CNS lymphoma were less likely than PML based on the patients lack of signs/symptoms of increased ICP.

PML:

Progressive multifocal leukoencephalopathy is an infection of oligodendrocytes by JC virus which manifests in  multifocal areas of demyelination throughout the brain.  The disease spares the spinal cord and optic nerves.  45% of patients present with visual defects which is typically a homonymous hemianopia or quadrantanopia.  38% present with mental impairment (dementia, confusion, personality change).  Hemi or monoparesis is common, as is ataxia.  Seizures can occur in about 20% of patients.  

80% of patients diagnosed with PML have HIV and nearly all have underlying immunosuppression.  About 5% of patients with HIV develop PML.  Also, people receiving monoclonal antibodies, especially natalizumab (used for MS and Crohn’s disease), efalizumab (Raptiva for psoriasis), and rituximab can make patients more susceptible.

Diagnosis:

Diagnosis is based on MRI findings.  MRI shows multifocal asymmetric, coalescing white matter lesion in the periventricular, parietal-occipital region, cerebellum, and centrum semiovale (cerebral white matter).  Lesions only rarely show ring enhancement.  The lesions are not associated with edema or mass effect (which is why our patient did not experience headache, nausea, vomiting).


Management:

CSF cell counts are usually normal, but PCR amplification of JCV DNA is 92-100% specific for PML in the setting of MRI findings.  Sensitivity is 70-90% or lower if the patient is taking antiretrovirals. 

Right now, there is no therapy shown to benefit in randomized controlled trials.  There is an ongoing active trial looking at mefloquine.  Any intervention to restore immunocompetence should be explored.  Typical survival is 3-4 months in untreated patients.  If HAART is introduced in AIDS patients, about half of the patients with live to 1 year. 

Take Home Message:

  1. In patients with AIDS with low CD4 counts presenting with focal neurologic deficits, toxoplasmosis, CNS lymphoma and PML are the most common diagnoses.
  2. PML can be differentiated from the others by lack of symptoms suggesting increased ICP. 
  3. The diagnosis can be further supported by MRI.
  4. There are no good treatments beyond improving the patient’s immunocompromised state (HAART or stopping offending immunosuppressants).
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