Arthur W. Clark

The Axonal Pathology in Chronic IDPN Intoxication

Neurofilamentous axonal swellings occur in a number of degenerative and toxic disorders of the nervous system. In one of these, experimental intoxication with β,β-irninodiproprionitrile (IDPN), accumulation of neurofilaments has been shown to result from a defect in slow axonal transport. The consequence of this functional abnormality is a series of changes in axonal morphology: Neurofilaments accumulate in the proximal axon; the proximal axon becomes swollen; the distal axon loses volume (axonal atrophy). These studies indicate that axonal atrophy occurs secondary to an impairment of slow axonal transport and suggest that a similar abnormality may underlie the pathological changes in certain other degenerative and toxic diseases of the nervous system.

Neurologic complications of bone marrow transplantation

Among 78 patients who died after bone marrow transplantation, neurologic complications were present in 55 (70%) and were the cause of death in 5 (6%). Metabolic encephalopathy occurred in 29 patients (37%). CNS infections included aspergillosis (3), herpes simplex encephalitis (2), and Listeria monocytogenes meningitis (1). Six additional patients had neuropathologic changes possibly due to cytomegalovirus infection. Cerebrovascular complications occurred in five patients (two hemorrhages and three infarcts). All infarcts were associated with endocarditis. The rate of nonbacterial thrombotic endocarditis was significantly higher (p < 0.001) than in the general autopsy population. CNS leukemia and therapy-induced injury were rare. There was no evidence of graft-versus-host disease involving the CNS.

Alzheimer's Disease and Down's Syndrome*

DONALD L . PRICE, t

Cortical degeneration with swollen chromatolytic neurons: Its relationship to Pick's disease

j PETER J . WHITEHOUSE,I ROBERT G. STRUBLE,t j JOSEPH T. COYLE,I[ ARTHUR W. CLARK,t

The nucleus basalis in Huntington's disease

MAHLON R. DELONG,

Paraplegia following intrathecal chemotherapy neuropathologic findings and elevation of myelin basic protein

LINDA C. CORK,t ( ( and J O H N C . HEDREENtj t Department of Pathology 1 Department of Neurology

Diaphragmatic paralysis in motor neuron disease Report of two cases and a review of the literature

Neuropathology Laboratory 7 Departments of Neuroscience, Psychiatry and Pharmacology and Experimental Therapy I( Division of Comparative Medicine The Johns Hopkins University School of Medicine Baltimore, Maryland 21205

Ocular Clinicopathologic Correlation of Hallervorden-Spatz Syndrome with Acanthocytosis and Pigmentary Retinopathy

We report two cases of dementia in which cortical degeneration with widespread swollen chromatolytic neurons (SCN) was the dominant pathologic feature. Each patient had received the diagnosis of Alzheimers disease on the basis of clinical findings. There was no deficit of cortical choline acetyltransferase activity, assayed in one case, or lesions of the nucleus basalis of Meynert. The brains had moderate to marked frontal atrophy. Comparison of SCN with several other cerebral degenerative disorders indicates a similarity with certain features of the transmissible spongiform encephalopathies and with corticodentatonigral degeneration. The pathologic features of our cases are those of a number of other cases reported as “Picks disease,” and may represent an earlier stage in the pathogenetic process than the severe, sharply circumscribed atrophy with “nonspecific” cell loss and gliosis as the only microscopic residuals. Our findings re-emphasize the need to search for pathogenetically distinct subgroups which have been wholly or partially subsumed into the concept of Picks disease.

Brainstem findings in Huntington's disease. Possible mechanisms for slow vertical saccades.

The nucleus basalis of Meynert (nbM) provides most of the cholinergic input to the cerebral cortex. The loss of cortical choline acetyltransferase (CAT) activity in Alzheimers disease (AD) and senile dementia of the Alzheimers type (SDAT) appears to be related to a severe depopulation of the nbM in this dementia. In Huntingtons disease (HD), by contrast, there is no loss of cortical CAT activity. The present quantitative study indicates that (1) there is no significant loss of neurons from the nbM in HD, and (2) that the previously described cytologic changes in the neurons of this nucleus in HD patients do not differ significantly from controls. These findings are consistent with the working hypothesis that the types of dementia associated with reductions of neocortical CAT activity are characterized by dysfunction or death of neurons in the nbM, but dementing disorders with normal neocortical CAT activity manifest no major abnormalities in this cholinergic nucleus of the basal forebrain.

Nonbacterial thrombotic endocarditis in bone marrow transplant patients

An 11‐year‐old boy developed a severe myelopathy after an eight‐year history of acute lymphoblastic leukemia and numerous courses of intrathecal chemotherapy. Myelin basic protein in the cerebrospinal fluid (CSF) was elevated. Neuropathologic examination disclosed extensive microvacuolar changes in the white matter of the spinal cord. The pathogenesis of myelopathy following intrathecal chemotherapy administered by lumbar puncture includes an early effect on the myelin sheath. Serial assessment of CSF myelin basic protein levels in patients receiving intrathecal chemotherapy may be useful in the early diagnosis of this disorder.