In this case, his aunt did provide the information that he was in multiple same-sex sexual relationships.

Test results obtained are as follows. The patient is human immunodeficiency virus (HIV)-positive with a viral load of 750,000 and a cluster of diff erentiation 4 (CD4) count of 61. Cerebrospinal fluid (CSF) analysis yielded protein level of 105. Polymerase chain reaction (PCR) for JC-virus was negative. CSF immunoglobulin G (IgG) index was high with nine oligoclonal bands (probable markers of demyelination and blood–brain barrier leakage).

• MRI of the brain shows extensive periventricular demyelination with some degree of atrophy. On the contrast images (not shown), there was no enhancement.

• Differential diagnosis is broad and includes the following¹:
  
  
  
  • Multiple sclerosis (lesions should typically enhance with contrast)
    
  • Acute disseminated encephalomyelitis (ADEM)
    
  • Progressive multifocal leukoencephalopathy (PML)
  
  
• Other less likely diagnosis include
  
  
  
  • Neoplasms (primary or metastatic – atypical as there is no enhancement, no mass eff ect, and lesions are diffuse)
    
  • Infectious causes (herpes encephalitis – atypical location)
    
  • Vascular (small vessel disease – also atypical location)
    
  • Medication or vitamin deficiencies (vitamin B6 [pyridoxine] deficiency)

• Important history facts to seek include
  
  
  
  • Medical and surgical history
    
  • Medications taken
    
  • Family history
    
  • Other social history
    
    
    
    • Drugs, alcohol, smoking
      
    • Diet history
      
    • Sexual contacts and relationships

• Toxicology screen
  
• HIV panel
  
• CSF analysis, including
  
  
  
  • Usual tests (cell count, cytology, cultures, glucose, protein)
    
  • Viral analysis – particularly PCR for JC-virus²
    
  • CSF immunoglobulin G index
    
  • Toxoplasmosis titers

• A brain biopsy may be considered if the tests remain inconclusive.
  
  
  
  • This is particularly useful in patients with AIDS who have intracerebral lesions and negative toxoplasmosis titers.³
  
  
• There is no focal lesion or mass effect. Therefore, there are no further indications for surgical intervention (aside from obtaining a diagnostic biopsy).⁴

• Overall yields range from 67–92%.^3,5–7
  
• In a study on 246 patients with AIDS, a definitive diagnosis was obtained in 92.3% of patients who underwent a biopsy.³
  
  
  
  • Lymphoma was the most frequent diagnosis (52.9% of patients).
    
  • This was followed by progressive multifocal leukoencephalopathy (18.9% of patients).
    
  • After lymphoma, toxoplasmosis (8.1% of patients) was the most frequently diagnosed.
  
  
• Of note, however, is that a contrast-enhancing lesion will yield a diagnosis more frequently than a non-contrast-enhancing lesion.
  
  
  
  
  • In a study on 25 AIDS patients, the proportion of biopsies of contrast-enhancing lesions that were diagnostic and contributing to the patients’ therapeutic management was 87.5%. However, only 67% of the biopsies of nonenhancing lesions were diagnostic, and none of these lesions were treatable.⁵

• HIV with AIDS
  
• Probable PML8
  
  
  
  • PML is a rare subacute demyelinating disease caused by an opportunistic papovavirus called JC-virus (JCV) or in some cases by the SV-40 strain.
    
  • It occurs in patients with defective cell-mediated immunity (2–5% of patients with AIDS), 9 in 1 in 1000 patients treated with Tysabri (Natalizumab; biogen idec, Cambridge, MA; immunosuppressant used in the treatment of multiple sclerosis),10 in patients with carcinoma and sarcoidosis, and in therapeutically immunosuppressed patients (e.g., transplant patients).
    
  • A few cases have been reported in the absence of underlying disease.
    
  • Pathology reveals eosinophilic intranuclear inclusions of papovavirus causing destruction of the oligodendroglia with relative sparing of axons.
    
  • Demyelination is most prominent in the subcortical white matter, with involvement of cerebellum, brainstem, or spinal cord white matter being less common.
    
  • With disease progression, the demyelinated areas coalesce to form large lesions.
    
  • Clinical manifestations are diverse and related to the location and number of lesions.⁹
    
    
    
    
    • Onset is subacute to chronic with focal or multifocal signs (hemiplegia, sensory abnormalities, visual field cuts, and other focal signs of lesion in the cerebral hemisphere).
      
    • Cranial nerve lesions, ataxia, and spinal cord involvement are less common.
      
    • Dementia ensues as the number of lesions increase.
    
    
  • A definitive diagnosis of PML can be made by brain biopsy.
    
  • CSF is usually normal.
    
  • JC virus DNA can be detected in CSF by nested PCR (n-PCR).¹¹

• There is no definitive treatment available for PML.
  
• Highly active antiretroviral therapy should be initiated with the goals as follows:¹²
  
  
  
  • Improvement of CD4 count
    
  • Normalization of viral load
    
  • Neurologic stabilization of PML symptoms

• The diagnosis of PML has an overall grim outlook.¹¹
  
• The course of PML usually lasts months with 80% of patients dying within 9 months.
  
• Rarely, survival may be several years, with the longest verified course being 6 years.