Case 697 -- A progressive multifocal neurological syndrome in a 42 year old woman

Contributed by Jane Cryan and Francesca M Brett
Department of Neuropathology, Beaumont Hospital, Dublin 9, Ireland.


A 42 year old female presented with transient new onset dizziness. She had a past history of a right posterior cerebral artery aneurysm in 1989 which was clipped and she had a residual left homonymous hemianopia. On examination at the time of her first presentation there were no additional findings. One year later she described intermittent headache, vertigo, difficulty speaking and her family noticed she occasionally used the wrong word. Now on examination she had mild dysarthria and a wide based ataxic gait. Plantars were down-going. There was no sensory abnormality and Romberg's test was negative.

Baseline blood tests showed a normocytic normochromic anemia which was explained by menorrhagia. ESR and CRP were normal, as was B12, folate, U&E, LFT's, TFT's, serum ACE, serum ANCA and a full autoantibody screen. A faint monoclonal IgG band was seen on serum protein electrophoresis but urine was negative for Bence Jones protein and there were no other features of multiple myeloma. CSF analysis showed no cells, and no oligoclonal bands. Testing for visual evoked responses was normal. The aneurysm clip was not MRI-compatible and so brain imaging was confined to CT. CT brain, which was repeated on a number of occasions during her illness, showed mild cerebellar atrophy, post surgical change in the region of the previous craniotomy site, as well as a right frontal wedge-shaped hypointensity which was felt to be consistent with an infarct (FIGURE 1). Vaginal ultrasound was normal. She was treated at various stages with plasma exchange and intravenous steroids and appeared to respond to same.

Her clinical course was progressive and she developed cognitive impairment with some features of frontal dementia. It was noted that her cognition fluctuated on a day to day basis such that her mini-mental state examination ranged from 16-26/30. She became progressively stiff and was unable to care for herself. She was transferred to a nursing home where she remained until her death which occurred 4 years after her first presentation. There was no diagnosis at the time of her death. The clinical differential diagnosis included multiple system atrophy, spinocerebellar ataxia, CJD, paraneoplastic syndrome among others. A complete autopsy was performed.


At autopsy the body was that of a very thin female with numerous contractures. The lungs showed focal bronchopneumonia. The heart, gastrointestinal and genitourinary systems, and breasts were normal. Specifically there was no evidence of tumour. Gross examination of the brain showed mild frontal atrophy. Serial coronal slices through the cerebral hemisphere showed striking abnormalities in the white matter with grayish discoloration of the white matter (FIGURE 2). The abnormality appeared to be predominantly in the white matter except in the region of the inferior horn of the lateral ventricle particularly on the left hand side where there was definite involvement of the grey matter (FIGURE 3). This discoloration was also seen in the brainstem, cerebellum and spinal cord. The most striking abnormality on microscopic examination is the presence of blood vessels in the leptomeningeal areas and throughout the grey and white matter which are filled with large atypical cells (FIGURE 4). These cells have large nuclei and prominent nucleoli (FIGURE 5). Mitotic figures are identified in these cells. Adjacent grey and white matter shows numerous small infarcts - some of which appeared quite recent with rarefaction of the neuropil. Others appear older with accumulation of hemosiderin- laden macrophages (FIGURE 6). Brain stem, cerebellum and spinal cord similarly show accumulation of malignant cells in the vessels with focal areas of infarction. Immunohistochemical stains of these cells were positive with B lymphoid markers, CD20 (FIGURE 7) and CD79a, whereas only a small number of small normal appearing CD3 positive T cells were identified in the region of some of these blood vessels (FIGURE 8). CD29 was negative in tumour cells.


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