Third ventriculostomy for internal hydrocephalus complicated by unrecognized subdural hygroma and hematoma: a case report of a patient treated by Dr. Walter Dandy.

The authors review the case of a patient treated by Dr. Walter Dandy. When the patient was a young child he underwent two right transtemporal third ventriculostomies during which he sustained an unrecognized contralateral subdural hygroma and a chronic subdural hematoma with a mild infantile hemiparesis. He was able to complete high school, albeit at a slower pace than usual. As an adult he held several limited employment positions, lived at home for several decades, and was later cared for at a nursing home for a short time. The patient died when he was 66 years of age.

Central diabetes insipidus due to cytomegalovirus infection of the hypothalamus in a patient with acquired immunodeficiency syndrome: a clinical, pathological, and immunohistochemical case study.

We report a case of central diabetes insipidus (CDI) in a patient with AIDS due to cytomegalovirus (CMV) infection of the vasopressin-producing areas of the hypothalamus. The clinical diagnosis is established by definitive clinical and laboratory evidence of CDI. Detailed histopathological and immunohistochemical studies establish CMV as the causative agent and demonstrate the deficit of vasopressin in the synthesizing neurons. Physicians caring for patients with AIDS should be aware of CDI and adipsic hypernatremia as potential complications of CMV infection. The case also demonstrates that patients with diabetes insipidus do not have polyuria when glucocorticoid deficiency coexists.

The neuropathology observed in wild-type mice inoculated with human poliovirus mirrors human paralytic poliomyelitis.

Human paralytic poliomyelitis results from the destruction of spinal cord anterior horn motor neurons by human poliovirus (PV). CNS disease pathology similar to human poliomyelitis has been observed in experimentally infected chimpanzees, monkeys and wild-type mice. In this study we present a detailed examination of the clinical and histopathological features in the wild-type mouse after intracranial (i.c.) and novel intramuscular (i.m.) injection of poliovirus. Either route of poliovirus administration results in a clinical disease characterized predominately by flaccid paralysis. The observed histopathological features are compared with the histopathology reported for human paralytic poliomyelitis, experimentally infected chimpanzees, monkeys and transgenic mice expressing the human poliovirus receptor (hPVR). The observation of flaccid paralysis and anterior horn motor neuron destruction mirrors what is observed in human paralytic poliomyelitis. Our results suggest that the neuropathology observed in the wild-type mouse model is similar to what has been observed in both the human disease and in other experimental animal models, with the possible exception of the transgenic mouse model. The observed neuropathology of the wild-type mouse model more closely reflects what has been observed in human poliomyelitis, as well as in experimentally infected chimpanzees and monkeys, than does the hPVR transgenic mouse model. The previously reported poliovirus-induced white matter demyelinating disease was not observed.

Association between conformational mutations in neuroserpin and onset and severity of dementia.

BACKGROUND: The aggregation of specific proteins is a common feature of the familial dementias, but whether the formation of neuronal inclusion bodies is a causative or incidental factor in the disease is not known. To clarify this issue, we investigated five families with typical neuroserpin inclusion bodies but with various neurological manifestations. METHODS: Five families with neurodegenerative disease and typical neuronal inclusions had biopsy or autopsy material available for further examination. Immunostaining confirmed that the inclusions were formed of neuroserpin aggregates, and the responsible mutations in neuroserpin were identified by sequencing of the neuroserpin gene (SERPINI1) in DNA from blood samples or from extraction of histology specimens. Molecular modelling techniques were used to predict the effect of the gene mutations on three-dimensional protein structure. Brain sections were stained and the topographic distribution of the neuroserpin inclusions plotted. FINDINGS: Each of the families was heterozygous for an amino acid substitution that affected the conformational stability of neuroserpin. The least disruptive of these mutations (S49P), as predicted by molecular modelling, resulted in dementia after age 45 years, and presence of neuroserpin inclusions in only a few neurons. By contrast, the most severely disruptive mutation (G392E) resulted, at age 13 years, in progressive myoclonus epilepsy, with many inclusions present in almost all neurons. INTERPRETATION: The findings provide evidence that inclusion-body formation is in itself a sufficient cause of neurodegeneration, and that the onset and severity of the disease is associated with the rate and magnitude of neuronal protein aggregation.

Identification of human T-cell leukemia/lymphoma virus type I antibodies, DNA, and protein in patients with polymyositis

OBJECTIVE: To investigate a possible association between human T cell leukemia/lymphoma virus type I (HTLV-I) and polymyositis (PM). METHODS: Sera and muscle biopsy samples from 9 Jamaican PM patients were compared with specimens from American HTLV-I positive PM patients and normal controls. Sera were evaluated for HTLV antibodies by enzyme-linked immunosorbent assay and Western blot. The biopsy samples were analyzed for HTLV-I/II DNA by polymerase chain reaction and were also immunohistochemically stained for HTLV gp46 envelope protein. RESULTS: Seven of the 8 Jamaican PM patients from whom sera were available were HTLV-I seropositive. The muscle biopsies of all 9 Jamaican patients demonstrated severe lymphocytic infiltration, cellular degeneration, myofiber atrophy, and fibrosis. Each muscle biopsy specimen contained HTLV-I DNA. Two of 6 samples demonstrated intense staining for HTLV-I gp46 in many of the invading mononuclear cells and weak staining for HTLV-I gp46 in many of the other specimens were weakly positive for gp46 in rare mononuclear cells. All controls specimens were negative for the presence of HTLV-I DNA and protein. CONClUSION: HTLV-I is associated with an inflammatory muscle disease characterized by direct invasion of the affected muscle by HTLV-I-infected mononuclear cells.(AU)