Contributed by David C. Spencer* and Lysia S. Forno+
*Department of Neurology and Neurological Sciences Stanford University and Hospitals
and the +Department of Pathology, VA Palo Alto Health Care System, Palo Alto, CA, USA.
Published on line in February 2000
This 77-year-old Hispanic-American man with a history of alcoholism and hepatitis C infection suffered severe bouts of recurrent hepatic encephalopathy. His liver disease came to attention six years prior to his death, with elevated serum transaminases, esophageal and rectal varices, and gastrointestinal bleeding. The episodes of hepatic encephalopathy partially responded to treatment with lactulose and neomycin. Initial neurologic evaluation revealed mild cognitive deficits, dysarthria, resting tremor of the right thumb and intention tremor bilaterally. Deep tendon reflexes were initially normal but subsequently became increased. Plantar responses were flexor on the right and extensor on the left. Gait was wide-based. His neurologic status declined over several years; he became unable to walk, and neuropsychological testing demonstrated severe global cognitive dysfunction. He died from end-stage liver disease and hepatocellular carcinoma. Laboratory testing revealed normal serum tests for B12, syphilis, thyroid function, and normal CSF studies for syphilis, cell count, glucose, and protein. CT scan of the head was normal.
GROSS AND MICROSCOPIC DESCRIPTION:
The only gross abnormalities were slight dilation of the lateral ventricles and a gray discoloration near the junction of cortex and white matter near the motor cortex. On microscopic examination there was striking vacuolation of the deep fronto-parietal cortex and adjacent white matter. (Fig. 1a, Luxol fast blue-PAS x 2.5). This change was seen to a varying degree in other cortical areas. Prominent pale vesicular astrocyte nuclei (Alzheimer type II glia) were seen in these regions of deep cortex, but were also present in other cortical areas and in the basal ganglia. Some Alzheimer type II glia in the deep cortex contained PAS positive intranuclear inclusions (Fig. 1b, arrows, Luxol fast blue-PAS x 550, oil immersion). These inclusions were demonstrated to be composed of glycogen by digestion with diastase. Some well-preserved Betz cells were seen adjacent to the vacuolated tissue. Electron microscopy (EM) from the deep sensorimotor cortex demonstrated focal vacuolation that sometimes could be seen within the cytoplasm of astrocytes (Fig 1c, arrows, x 7,500). The vacuolation appeared to be due mainly to disruption of astrocytes.
The spinal cord was severely affected, with loss of myelinated axons in the lateral corticospinal tracts, but also to a lesser extent in the posterior columns (Fig. 2, arrows, luxol fast blue-cresyl violet, x 7). These changes were seen from the cervical to lumbosacral levels of the cord, with sparing of corticospinal tracts above the level of the spinal cord. No Alzheimer type II glia were seen in the spinal cord. Sections from the thoracic cord showed two areas of vacuolation near the anterior horn that were separate from the tract degeneration (Fig. 2, arrowheads).