Progressive Multifocal Leukoencephalopathy in an Immunocompetent Patient?
A 72-year-old female was admitted to her local hospital because of right-sided hemiparesis and dysphasia. She had a history of well-regulated hypertension and total alopecia at age 40 years with spontaneous improvement. She had no known risk factors for immunosuppression. Her mother had suffered a stroke at the age of 70 years and no other family history of disease was reported. Three months prior to admission, the patient noted fluctuating small, red, itchy skin eruptions without fever or other accompanying infection signs. CT of the brain showed a hypodense lesion in the left parietal region, considered to be of vascular genesis. Acetylsalicylic acid and simvastatin were added to her antihypertensive medication.\nOne month later, a gradual worsening occurred. Three months after the initial neurological signs, a new CT scan revealed an enlarged hypodense lesion in the left parietal region and a minor lesion in the right dorsal parietal region. The patient's condition deteriorated considerably with increasing neurological symptoms, personality changes, aphasia, apraxia and right-sided hemiplegia.\nLaboratory tests showed a normal hemoglobin level and white blood cell and neutrophil counts. The lymphocyte count was low (12–15%; normal range 21–43) with low levels of serum IgG (4.7 g/l; normal range 6.1–14.9) and IgM (0.2 g/l; normal range 0.4–2.1), but a normal IgA level and no monoclonal component were seen. C-reactive protein, SR level, antinuclear antibodies, antineutrophil cytoplasmic antibody, double-stranded DNA, cardiolipin antibodies and rheumatoid factors were normal. No kidney, liver or thyroid abnormalities were observed. Cancer marker tests were normal. Serological tests for Epstein-Barr virus, cytomegalovirus, borrelia and syphilis were all negative. An HIV test was not performed. CSF analysis revealed a normal cell count and normal protein and glucose levels; there was no sign of intrathecal immunoglobulin synthesis. PCR for neurotropic viruses (herpes simplex virus, varicella zoster virus, cytomegalovirus, Epstein-Barr virus and enterovirus) and borrelia were negative. The electroencephalogram showed bilateral theta and delta waves, but no epileptic activity.\nA whole-body CT scan revealed bilateral kidney cysts, but no sign of malignancy or other pathological findings. MRI of the brain showed widespread white-matter lesions in both hemispheres, more extensively on the left side involving the frontal, parietal and occipital lobes (fig. ). The lesions were localized in the subcortical white matter. Examination revealed several small foci on contrast-enhancement in the right parietal lobe. Restricted diffusion was not noted. Magnetic resonance spectroscopy performed with multivoxal chemical shift technique over the right frontoparietal lobe showed unspecific changes with an elevated choline-to-creatine ratio and reduced N-acetylaspartate levels.\nThe patient deteriorated and the planned stereotactic brain biopsy was not performed because of her poor condition. She gradually progressed to a vegetative state. She passed away from the cardiopulmonary complications of bilateral bronchopneumonia 5 months after the first signs of disease.\nThree days later an autopsy was performed. The bilateral bronchopneumonia, moderate coronary atherosclerosis, bilateral kidney cysts and cholecystolithiasis were confirmed. A 13-mm tumor in the ileum without atypia was detected on histopathological examination. The brain was macroscopically atrophic, most prominently in the frontal and parietal lobes. Multiple confluent demyelination foci were described in both hemispheres, but not in the brainstem or the cerebellum. The microscopic examination revealed areas with demyelination, a variable number of macrophages, enlarged purple-stained oligodendroglial nuclei and massive gliosis with gemistocytic astrocytes, some with bizarre nuclei (fig. ). Electron microscopy showed intranuclear inclusions, and the in situ hybridization confirmed JC virus. The autopsy diagnosis was consistent with PML.