Hemiplegic amyotrophy. Muscle and motor point biopsy study.

Thirty hemiplegic patients had simple muscle atrophy with reduced mean muscle cross sectional areas (predominantly type II fiber atrophy) and complex, multiple, or enlarged subneural apparatuses, many of which resembled subhuman endplates. Ultrastructural observations in a few patients revealed nonspecific responses of damage to sarcolemma and myofibrils. There was no correlation between structural changes and alteration of tone, sensory impairment, or site of lesion. We propose that hemiplegic amyotrophy results from a combination of disuse, loss of central "trophic" influence, and transsynaptic degeneration.

St Louis encephalitis. Quantitative histologic and immunofluorescent studies.

Using techniques of stereology, we measured the severity of lesions in ten cases of acute St Louis encephalitis (SLE) from the 1975 epidemic in northern Illinois. Percentage of fractional volume and numerical profile density on area (N/A) of cellular nodules and N/A of blood vessels with perivascular inflammatory cellular infiltration were significantly correlated in 17 anatomic regions of the CNS. Ranking of the severity of lesions in these regions agreed with subjective estimates of other cases of SLE. Immunofluorescent tests established the presence of SLE viral antigen in cell bodies of neurons. Our findings contribute to better understanding of the pathology of SLE in man.

Inclusion body myositis. A corticosteroid-resistant idiopathic inflammatory myopathy.

In seven patients with slowly progressive muscle weakness, inclusion body myositis (IBM) was diagnosed on biopsy. None had stigmata of collagen-vascular disease or malignancy. Serum creatine kinase levels were mildly or moderately increased. The six patients treated with prednisone did not improve. Needle electromyography showed a "myopathic" pattern in all patients, but four also had diffuse neurogenic changes with normal nerve conductions. Histologic study of muscle showed a mixture of small rounded fibers varying in size, atrophic angulated fibers forming small groups, and hypertrophic fibers. Variable amounts of inflammation, necrosis, and regeneration were seen in all specimens. All showed numerous intracytoplasmic vacuoles lined with purple-blue granules. Electron microscopy showed membranous whorls and masses of abnormal filaments measuring 14 to 18 nm in diameter. Although IBM seems to be a distinct type of inflammatory myopathy, its etiology and pathogenesis are not clear.

Dementia of the Alzheimer's type and Huntington's disease.

At age 48, a man with a family history of Huntington's disease developed nervousness, depression, chorea, and dementia. He died at age 68, and his brain showed characteristic findings of both Huntington's disease and Alzheimer's disease. Only one other patient has had neuropathologic findings of both diseases.

Thalamic neuroaxonal dystrophy and dementia in Hodgkin's disease.

The brain of a patient with Hodgkin's disease and dementia showed numerous dystrophic axons in the thalamus. In absence of lymphomatous cellular infiltration, necrosis, hemorrhage, demyelination, neuronal loss, or infection by opportunistic organisms, the axonal dystrophy in this patient appeared to be directly related to the Hodgkin's disease itself. Moreover, dementia as a nonmetastatic complication of Hodgkin's disease may have been the result of the thalamic axonal dystrophy.

Myositis of chronic graft versus host disease.

A 13-year-old girl with chronic graft versus host disease (GVHD) developed severe proximal weakness. Muscle biopsy showed necrotic fibers with anti-IgG deposits and interstitial inflammation. Steroid treatment helped, but her weakness recurred. Repeat biopsy showed persistent inflammation and possible steroid myotoxicity. Numerical ratio of capillaries to myofibers and capillary numerical density were higher than childhood dermatomyositis (CD), and capillaries had no tubuloreticular inclusions. Absence of quantitative histologic, ultrastructural, or immunocytochemical abnormalities of capillaries differentiated our patient from CD. We conclude that myositis of chronic GVHD can present as a severe myopathy that responds to steroids and differs from CD.

Viruslike particles in granulomatous angiitis of the central nervous system.

Neuropathologic examination of the brain of a 67-year-old woman with a 5-month history of progressive multiple neurologic deficits showed granulomatous angiitis of the small parenchymal and leptomeningeal blood vessels of the brain and spinal cord. Electron microscopy of formalin-fixed brain disclosed intranuclear viruslike particles resembling herpesvirus. Although definitive proof cannot be established without further virologic tests, this previously unreported finding suggests that some cases of granulomatous angiitis of the central nervous system may result from viral infection.

Centronuclear myopathy in the newborn period causing severe respiratory distress.

Centronuclear myopathy can be classified into four clinical varieties based on age, severity at onset, and rapidity of progress. In the severe form with involvement of respiratory muscles at birth, the progress is rapid and fatal before 3 years of age. The case described in this report illustrates rapid progression of muscle paralysis and death in a neonate. However, in a majority of cases the disease is either moderately severe or mild with the affected individuals confined to wheel chair by adolescence or early adult life. Diagnosis of the disease is based on appropriate muscle histopathology and electron microscopic studies.

Clozapine eligibility: the effect of stringent criteria on ethnic, gender and age subgroups of schizophrenic patients.

1. The purpose of this retrospective chart review study was to determine whether broad and stringent criteria differentially impact clozapine eligibility in ethnic, gender, and age subgroups of schizophrenic patients. 2. 505 patients charts were selected from a random cluster sample of mental health patients known to the city and county of San Francisco. Information related to clozapine eligibility was abstracted by trained non-clinical personnel. The impact of subgroup membership on eligibility was examined using logistic regression procedures. 3. Even under the broadest interpretation of FDA requirements for clozapine use, Asian patients were less likely to be eligible, since fewer Asian patients met clozapine treatment requirements. Under more stringent eligibility criteria, older patients were more likely to be excluded from eligibility when TD does not automatically satisfy treatment criteria, and younger patients were more likely to lose eligibility if the number of required adequate medication trials increases to three. 4. Broad eligibility criteria tend to differentially exclude Asian patients while more stringent criteria differentially exclude younger and older patients.

Intrathecal paraganglioma of the cauda equina.

A 33-year-old obese woman with chronic pain in her lower back presented with weakness of her right quadriceps and diminution of her patellar reflex. Her myelogram revealed an intradural oval mass at level of the interspace between her 3rd and 4th lumbar vertebrae. Operation disclosed an encapsulated mass attached to her filum terminale. Histopathological examination showed a paraganglioma with typical dense core granules, confirmed by electron microscopic examination. We report our patient to call attention to intrathecal paragangliomas as a rare and treatable cause of the cauda equina syndrome.

Imprints, smears, and frozen sections of brain tumors.

In this study, we compared the suitability and accuracy of imprints, smears, and frozen sections of suspected brain and spinal cord tumors of 150 patients. Eighty-six percent of the imprints, 91% of the smears, and 99% of the frozen sections were suitable for interpretation. Among the suitable preparations, 82% of the imprints, 92% of the smears, and 99% of the frozen sections agreed with our diagnosis on paraffin sections. Although frozen sections were clearly more accurate than imprints and smears, the latter two provided diagnoses in patients with acquired immunodeficiency syndrome where frozen sections were not done to avoid contaminating our cryostat and in a patient with an epidermoid cyst of the middle fossa that could not be adequately frozen sectioned. Our study shows that imprints and smears complement frozen sections in the intraoperative diagnosis of tumors of the central nervous system.

Aneurysmal bone cyst of the thoracic spine: treatment by excision and segmental stabilization with Luque rods.

Preoperative radiological evaluation with magnetic resonance imaging and computed tomography was valuable in planning the surgical management of a destructive lesion of the posterior elements of the thoracic spine that was causing spinal cord compression in an 18-year-old woman. Preoperative recognition of bilateral involvement of the pedicles in addition to the laminae and spinous process led to use of prophylactic segmental stabilization of the spine with Luque rods after successful excision of an aneurysmal bone cyst. This case provides an example of the usefulness of computed tomographic scanning and magnetic resonance imaging in assessing the distribution and location of vertebral tumor and its potential effect on spinal stability. The efficacy of combining radical excision with stabilization for treatment of aneurysmal bone cysts of the spine is emphasized.

The aging substantia nigra: quantitative histologic study.

In this study, we estimated the amount of neuronal neuromelanin in hematoxylin and eosin sections of the pars compacta of the substantia nigra in 69 autopsied subjects, 14 to 100 years old. The mean area of cellular neuromelanin showed a curvilinear increase from 103 microns2 at age 14, to 600 at age 67 before dropping off to 328 at age 100 (R2 = +0.51, p < 0.00001). By contrast, the areal fraction or area of neuromelanin relative to the area of neuronal cell bodies showed a linear increase with age (r = +0.84, p < 0.00001). The latter and an increase in the percent of neuromelanin pigmented neuronal cell bodies from 83% at age 14 to almost 100% at age 65 and older (R2 = +0.61, p < 0.00001) accounted for the increasing mean area of cellular neuromelanin. By contrast, a decrease in the mean area of neuronal cell bodies (r = -0.63, p < 0.00001) and a decrease in the number of profiles of neuronal cell bodies (r = -0.51, p < 0.0001) explained the decrease of mean area of cellular neuromelanin beyond 67. Our findings support the hypothesis that an overload of neuromelanin is neurotoxic and emphasize the importance of using age-matched controls in histopathologic studies of the substantia nigra.

Histopathology of the substantia nigra in Alzheimer's disease.

Histopathologic examination of the pars compacta of the substantia nigra of 17 patients with Alzheimer's disease showed Lewy bodies in six, neurofibrillary tangles in another six and only histologic changes that did not differ from age-matched controls in five patients. Four of the six patients with nigral Lewy bodies showed severe loss of neural cell bodies, reactive astrocytosis, gliosis and neuromelanin in macrophages and in the neuropile. By contrast, the loss of neuronal cell bodies in our patients without nigral Lewy bodies regardless of whether or not they also had nigral neurofibrillary tangles was no greater than what we observed in our age-matched controls. Quantitative cell counts confirmed our histopathologic estimates of neuronal loss. Our study and the findings of others show that the substantia nigra is often abnormal in Alzheimer's disease and that the abnormalities are rarely severe without nigral Lewy bodies.

Zebra body myopathy: a second case of ultrastructurally distinct congenital myopathy.

Biopsy of the deltoid muscle of a 4-day-old baby boy with congenital hypotonia and weakness showed zebra bodies and other myopathic changes. Our patient and an other patient reported in the literature establish zebra body myopathy as an ultrastructurally distinct benign congenital myopathy.

Neural defects in Jarcho-Levin syndrome.

Neuropathologic examination of two autopsied patients with Jarcho-Levin syndrome showed no pathologic changes in the brain, spinal cord, or nerve roots of one and diastematomyelia of the thoracolumbar spinal cord in the other. The abnormalities of the spinal cord in one of our patients and in another patient described in the literature establish neural defects as a component of the Jarcho-Levin syndrome.

Periductal elastic tissue of breast cancer. Quantitative histologic study.

Using techniques of stereology, we estimated the relative volume of periductal elastic tissue in 60 infiltrating ductal carcinomas of the breast. Volume density of periductal elastic tissue in the neoplasm correlated with our own subjective histologic estimates of the amount of elastic tissue. Periductal elastic tissue had a significantly higher volume density in the neoplasm than in nonneoplastic breast, but the two estimates did not correlate with each other. Similarly, the volume density of elastic tissue in the neoplasm did not correlate with that of neoplastic cells or of stromal collagen in the neoplasm, degree of lymphocytic infiltration, lymph node metastasis, mortality, menstrual status, age, parity, or presence or levels of estrogen receptor protein in the neoplasm. On the other hand, parity correlated with the volume density of periductal elastic tissue in the nonneoplastic parenchyma of the breast. Our findings indicate that there are at least two separate elastogenic effects in infiltrating ductal carcinoma of the breast: that exerted by parity on nonneoplastic tissue and that exerted by cancer itself on the neoplasm.

Effects of stringent criteria on eligibility for clozapine among public mental health clients.

OBJECTIVE: This study estimated rates of eligibility for treatment with clozapine among clients in a public mental health system using criteria with various degrees of restrictiveness. METHODS: A stratified, random cluster sample of 293 clients was selected from among all clients with schizophrenic disorders known to the mental health system of the city and county of San Francisco during 1991. Data on variables associated with eligibility for clozapine were abstracted from clinical records, and eligibility was estimated using broad and stringent criteria. RESULTS: An estimated 42.9 percent of the clients were eligible for clozapine using broad eligibility criteria that included a diagnosis of schizophrenia or schizoaffective disorder, two previous neuroleptic trials of at least 600 mg per day chlorpromazine equivalents for at least four weeks or tardive dyskinesia, Global Assessment of Functioning score less than 61, and no contraindications. Eliminating eligibility due to tardive dyskinesia alone, excluding persons with schizoaffective disorder, requiring six-week medication trials, and requiring three adequate medication trials instead of two resulted in substantial reductions in the rate of eligibility. CONCLUSIONS: Varying interpretations of the criteria for clozapine treatment listed in the medication package insert dramatically affect patients' eligibility for clozapine. Mental health agencies should endeavor to maintain a balance between restricting use of clozapine due to cost and providing it to the full spectrum of patients who might benefit from the medication.

Malignant lymphoma presenting as a chronic subdural hematoma.

A 56-year-old man had a right frontotemporoparietal craniotomy for evacuation of an encapsulated subdural hematoma that had reaccumulated after burr-hole decompression 6 weeks before. Histopathologic examination showed a malignant lymphoma in the subdural hematoma. Our patient shows that malignant lymphoma can rarely present as a chronic subdural hematoma.