Contributed by Alexander Easton, MBBS, PhD
Department of Laboratory Medicine and Pathology, Walter C Mackenzie Health Sciences Centre, Edmonton, Alberta, Canada, T6G 2R7
Published on line in October 2005
CLINICAL HISTORY AND RADIOLOGY:
This 48 year old male presented in October 2000 with sudden (<12 hours) right sided weakness. His admission blood pressure was 178/107. Nervous system examination found reduced visual acuity but no double vision or visual field defects. Right sided power was reduced to 0/5 (right arm) and 3/5 (right leg), with normal tone, reduced bulk and increased reflexes. Plantars were bilaterally up-going with ankle clonus. Admission CT scan showed a 3cm (transverse) x 2cm (sagittal) deep left intracerebral hematoma with surrounding edema. The occipital horns of the lateral ventricles were compressed by bilateral hypointense white matter lesions (figure 1). The patient became unresponsive the day after admission, with bilateral fixed pupils and a repeat CT showed hematoma expansion with new onset left uncal herniation. The bilateral white matter hypointensities were unchanged. Despite further treatment, on this day, with family consent, the patient was extubated and expired. Consent was given to perform a complete autopsy.
In 1995 he underwent liver transplantation for end stage cirrhosis from ethanol and hepatitis C, and was placed on cyclosporin. Hepatic artery stenosis developed and warfarin was commenced in 1999. In 1996 type 1 diabetes mellitus was diagnosed and treated with insulin. In June 2000 he developed microangiopathic hemolytic anemia with thrombocytopenia, secondary to thrombotic thrombocytopenic purpura (TTP), attributed to cyclosporin. In July 2000, acute renal failure led to dialysis and a kidney biopsy showed membranoproliferative glomerulonephritis superimposed on diabetic nephropathy with focal arteritis. From August 2000 significant hypertension developed (clinic values: 181-200/100-118) which was resistant to drug therapy. The patient had failing vision for several months, attributed to diabetic retinopathy.
From the general autopsy, the kidneys showed a thrombotic microangiopathy superimposed on end-stage diabetic nephropathy. The spleen showed red pulp expansion from immunosuppressive treatment. The transplanted liver showed no rejection features.
The formalin fixed brain weighed 1675g. There was bilateral hemispheric swelling and expansion of the left uncus. Coronal sections revealed a left sided hemispheric hematoma, extending from the frontal pole to the hippocampus. Beginning at the caudal limit of the calcarine sulcus, diffuse softening and grey-green discoloration of white matter was found in the occipital lobes bilaterally, extending to the occipital poles. This spared subcortical regions. Scattered petechial hemorrhages (up to 5mm) were noted in the occipital cortex overlying these regions (figure 2).
Microscopy showed an acute left frontal hematoma with early tissue infarction. Hypertensive arteriopathy was absent in the basal ganglia. The occipital white matter showed zones of diffuse pallor that spared the subcortical zones. Pallor was present on sections stained with Bielschowsky/silver (for axons) and Luxol fast blue (for myelin; figure 3). There was therefore, compared to normal brain, a reduced density of both axons and myelin with no loss of oligodendrocytes. Focal acute hemorrhages were noted in the parenchyma and around small arterioles, but vessels were structurally normal. In addition, perivascular spaces were expanded with small parenchymal cysts (figure 3). Cortical lesions consisted of scattered parenchymal hemorrhages associated with intraluminal microvascular thrombi and perivascular fibrin exudates (figure 4). A single cortical microinfarct was found, aged over 1 week. These cortical changes were confined to the occipital lobes.