Clinico-Pathological Conference Progressive multifocal leukoencephalopathy in patients with AIDS: detection ofJC virus DNA in CSF and brain

MRI Unit, Department of Imaging, Middlesex Hospital, London WlN 8AA R J S Chinn Correspondence to: Dr R F Miller, Department of Medicine, UCLMS, Middlesex Hospital, London WIN 8AA, UK. Accepted for publication 7 June 1994 Case presentations (Dr R F Miller) Case 1 A 56 year old right handed Caucasian homosexual unemployed laboratory technician was admitted as an emergency in March 1993 via the accident and emergency department, with the sudden onset of slurred speech, left facial weakness and falling to the right. On specific enquiry he denied loss of consciousness, visual disturbances or headache; he felt generally weak and tired and had no other symptoms. He was first found to be HIV-1 antibody positive in April 1987 and participated in the MRC Concorde Study until March 1992, at which point he developed oral candidiasis and a mild peripheral sensory neuropathy: his CD4 count had fallen to 190/mm.3 At this time he began co-trimoxazole as primary prophylaxis against pneumocystis pneumonia and "open label" zidovudine. This latter medication produced neutropenia and it was stopped; he began dideoxyinosine (ddl). On examination he was orientated in time and place but had a short attention span; he had dysarthria but no dysphasia. Neurological examination revealed left sided neglect, a left upper motor neuron seventh cranial nerve palsy and left sided weakness in both arm and leg. There was an extensor left plantar and also the palmar-mental and grasp reflexes were both brisk (suggesting a frontal lesion). Investigations revealed: haemoglobin = 12-7 g/dl, WBC = 4-1 (neutrophils = 3 3) x 109/1; Urea and electrolytes and liver function tests were normal. Serum toxoplasma and syphilis serology and cryptococcal antigen (CRAG) were negative. Culture of blood was negative for bacteria, mycobacteria and fungi. CT of the head showed a right frontal low attenuation lesion without enhancement and without mass effect. At lumbar puncture the cerebrospinal fluid (CSF) was clear and colourless; analysis showed protein = 1-82 g/l; no cells were seen. Gram, Auramine, India ink stains and culture for bacteria, mycobacteria, fungi and viruses were negative. DNA amplification, using the polymerase chain reaction (PCR) for Herpes simplex virus 1 and 2, cytomegalovirus (CMV) and varicella zoster virus DNA was negative. Empirical antitoxoplasma therapy was begun with sulphadiazine and pyrimethamine, but this produced a widespread maculopapular rash after 10 days of therapy and so it was stopped. MRI was performed. MRI scan (Dr R Jf S Chinn) This showed agenesis of the corpus callosum (an incidental finding). A focal region of high signal intensity was seen in the right frontal white matter on T2 weighted imaging (fig 1). This extended out into the gyral cores sparing the cortical grey matter. It also extended inferiorally along the white matter tracts through the internal capsule and crus cerebri into the right side of the pons. This lesion was of low signal intensity on TI weighted imaging (fig 2). It did not enhance after the administration of intravenous gadolinium-DPTA. There was no mass effect associated with this lesion. There were further similar small lesions in the right cerebellar hemisphere and in the right temporal lobe. These appearances were most likely to be due to progressive multifocal leukoencephalopathy.