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Increasing emphasis on interdisciplinary medical treatment and education suggests that something valuable has arisen from medical specialization beyond the further development of specialty knowledge: an integration of specialty knowledge that compliments and extends the integrating aspects of the primary care approach to medicine. Several educational models have been described which serve this function. In this paper the authors describe interdisciplinary clinical teaching, and research team linking neurology, neuroradiology, psychiatry and neuropsychology. The team provides neurobehavioural evaluations and sponsors monthly Neurobehaviour Rounds, an interdisciplinary patient conference that is the main formal teaching vehicle for the programme. After the model had been in place for 1 year, eight of nine neurology residents had Residency In-Service Training Examination scores in behavioural neurology that exceeded their overall average scores. This suggests that encouraging neurology residents to see patients through the eyes of different specialists may have contributed to improvement in their performance on a test of interdisciplinary knowledge. A neurobehavioural programme anchored to a formal neurobehaviour conference may encourage interdisciplinary learning within the related disciplines of neurology, neuropsychology and psychiatry.

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This study was designed to examine the sequential changes in the developing granuloprival cerebellar culture. In this model of anomalous cerebellar development, organotypic cultures derived from newborn Swiss-Webster mice were exposed to the DNA synthesis inhibitor, cytosine arabinoside, at explantation and were fixed for electron microscopic examination on successive days in vitro. Similar developmental stages were compared in control explants. Granule cell destruction began early, and was widespread by 2 days in vitro, when oligodendrocyte destruction also began in treated cultures. A few granule cells survived, but no recognizable oligodendrocytes remained by 7 days in vitro, at a time when myelin was initially evident in control explants. Purkinje cell recurrent axon collateral sprouting began at 3 days in vitro in cultures exposed to cytosine arabinoside, and the sprouted terminals initially synapsed with Purkinje cell somata, somatic spines and dendritic shafts. Synapses with Purkinje cell dendritic spines developed later, at approximately the same time as parallel fiber-Purkinje cell dendritic spine synapses formed in control cultures. Astrocytic ensheathment of control Purkinje cells was well underway by 6 days in vitro and Purkinje cell somata were relatively rounded and almost completely ensheathed by 9 days in vitro. Glial ensheathment did not occur in cytosine arabinoside treated cultures, and Purkinje cell somata were scalloped at 7 days in vitro by excess impinging recurrent axon collateral terminals, and never developed the smooth contours characteristic of control Purkinje cells. Purkinje cell somatic spines persisted in treated explants, and reduction of excess extracellular space was delayed until 12 days in vitro, when most of the developmental changes had been completed. The earlier development of synapses by excess recurrent axon collateral terminals with Purkinje cell somata, somatic spines and dendritic shafts, followed by the later development of heterotypical synapses with dendritic spines, in parallel with synapse formation by normal presynaptic elements, suggests that the sequence of development of synapses is a function of the maturational state of the postsynaptic components.

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During a 2-year period, 256 patients were screened for cervical radiculopathy and myelopathy with surface-coil MR images and plain films. Selected patients had follow-up examinations including CT, myelography, and CT myelography. Thirty-four of these patients underwent cervical spine surgery after MR imaging, which disclosed a total of 50 abnormalities in three major categories: herniated disks, bony canal stenoses, and intradural lesions. MR correctly predicted 88% of all surgically proved lesions compared with 81% for CT myelography, 58% for myelography, and 50% for CT. Missed herniated disks on either MR or CT myelography usually were the result of technically suboptimal studies caused by motion artifacts on MR and beam-hardening artifacts on CT myelography. Small osteophytes adjoining herniated disks sometimes were not predicted on MR, although such osteophytes invariably were seen on plain films and were palpable during standard anterior cervical diskectomy procedures. Herniated disks in the lateral root canals found in two patients appeared to be detected more readily by CT myelography than by MR. All proved lesions were detected by either screening MR images and plain films or by follow-up CT myelograms. MR replaced invasive evaluations by myelography and CT myelography in 32% of preoperative patients. We conclude that MR images, combined with plain films, offer an accurate, noninvasive test for the preoperative evaluation of cervical radiculopathy and myelopathy, while CT myelography is the preferred follow-up examination.

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We have detected a disorder in Korat cats (initially imported from Thailand) that is analogous to human Sandhoff's disease. Pedigree analysis indicates that this disease in an autosomal recessive disorder in the American Korat. Postmortem studies on one affected cat showed hepatomegaly that was not reported in the only other known feline model of GM2-gangliosidosis type II. Histologic and ultra-structural evaluation revealed typical storage vacuoles. There was a marked deficiency in the activity of hexosaminidase (HEX) A and B in affected brain and liver as compared to controls. Electrophoresis of a liver extract revealed a deficiency of normal HEX A and B in the affected animals. The blocking primary enzyme immunoassay verified the presence of antigenically reactive HEX present in affected cat livers in quantities slightly elevated with respect to the normal HEX concentration in control cats. In leukocytes, obligate heterozygotes had intermediate levels of total HEX activity with a slight increase in the percent activity due to HEX A. Indeed, 4 of 11 phenotypically normal animals in addition to four obligate heterozygotes appear to be carriers using this assay. Affected brain and liver compared with control brain and liver contained a great excess of bound N-acetylneuraminic acid in the Folch upper-phase solids; thin-layer chromatography showed a marked increase in GM2-ganglioside. In summary, we have characterized the pedigree, pathology, and biochemistry of a new feline model of GM2-gangliosidosis which is similar to but different from the only other known feline model.

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It has been shown that transplanted central nervous system tissue containing oligodendrocytes will myelinate neuronal processes in vitro and in situ. In this study we propose to show that cultured rat oligodendrocytes have the capacity to myelinate mouse cerebellar neuronal processes in vitro. Cultured rat oligodendrocytes were transplanted to cytosine arabinoside-treated mouse cerebellar explant cultures, then observed for myelination. Ultrastructural examination showed myelin and myelin-like figures in co-cultures. Control cytosine arabinoside-treated cultures and cultured oligodendroglia were without compact myelin.

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A 15-year-old boy presented with hydrocephalus due to a pineal tumor presumed to be a germinoma. After a shunting procedure, gross total tumor resection was carried out via an occipital transtentorial approach. Histopathological examination of the tissue demonstrated that, in addition to the expected germinoma, the tumor also contained areas of astrocytoma and areas that, taken in isolation as in a needle biopsy, could have been diagnosed as pineocytoma. The diagnosis and therapy of a pineal tumor of mixed histological types such as this lesion would be seriously compromised by "conventional" empiric radiation and even a stereotactic needle biopsy may not have provided an adequate tissue sample.

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In a rodent model of Escherichia coli brain abscess, the natural history of the infection was studied and the influence of a glucocorticoid (dexamethasone) and an antibiotic (gentamicin) on the development of brain abscess and the survival of abscess-bearing animals was evaluated. The administration of steroids using three different dosage schedules suppressed the macrophage and glial response, decreased collagen formation, increased the number of pathologically evident bacteria, and decreased host survival. The administration of antibiotics by parenteral routes decreased the number of viable bacteria in the abscess. The simultaneous administration of systemic gentamicin and dexamethasone resulted in increased host survival to a level that was intermediate between that of animals treated with dexamethasone alone and that of those treated with gentamicin alone. Thus, some of the adverse effect of corticosteroids on host survival could be mitigated by the simultaneous administration of antibiotics. Finally, it was observed that the abscess in this model tends to expand along white matter tracks. This path of least resistance may be responsible for the observation that brain abscesses tend to rupture into the ventricle rather than into the subarachnoid space via the cortex.

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We have studied a 17-year-old girl with lactic acidosis (3-18 mEq/liter) and progressive muscle weakness since 9 years of age. Morphological findings in muscle were of a typical ragged red myopathy with multiple collections of bizarre mitochondria, some containing paracrystalline inclusions. The carnitine content of serum and muscle was normal, as were the activities of carnitine palmitoyltransferase, carnitine octanoyltransferase, and carnitine acetyltransferase in the patient's muscle. Measurement of the enzymes of oxidative phosphorylation in both crude muscle homogenates and mitochondrial fractions showed close to normal activities of cytochrome c oxidase, succinate dehydrogenase, and ATPase. In contrast, succinate cytochrome c reductase activity was greatly reduced in the patient, being 0.035 mumol/min/g tissue in whole muscle (controls 1.16 +/- 0.47 mumol/min/g tissue) and 8 nmol/min/mg protein in the mitochondria (control, 340 nmol/min/mg protein). Rotenonesensitive NADH-cytochrome c reductase was also undetectable in the patient's mitochondria. Spectral analysis of cytochromes showed decrease of reducible cytochrome b to 16% of the control. These results indicate a defect of ubiquinol-cytochrome c reductase or the cytochrome bc1 segment (complex III) of the electron transport chain. Antibody-binding studies of the individual components of complex III showed additional deficiencies of core proteins I and II and peptide VI, indicating a more widespread defect of complex III than was evident from spectral analysis and enzyme activity measurements alone. Urine organic acid analysis after fasting and following a medium chain triglyceride load showed unusually high levels of lactate and 3-hydroxybutyrate, lower than expected levels of acetoacetate and dicarboxylic acids, and the presence of several other metabolites suggesting a disturbed citric acid cycle and redox state.(ABSTRACT TRUNCATED AT 250 WORDS)

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Antibiotics vary widely in their ability to penetrate the blood-brain barrier. In studies of 70 rats, the permeability of the normal blood-brain barrier to gentamicin was shown to be poor. In experimental brain abscesses, during the cerebritic stage of development, the penetration of intravenous antibiotics was increased compared to normal brain but was very inconsistent. Antibiotic delivery to brain abscess was not significantly altered with the administration of high-dose steroids, but the macrophage and glial response was markedly decreased with high-dose steroid therapy. Reversible osmotic blood-brain barrier modification with mannitol increased the delivery of gentamicin both to brain abscess and to the surrounding brain. It also resulted in more consistent tissue drug levels. The clinical implications of these studies suggest that, because of the inconsistent delivery of gentamicin to brain abscess, the therapeutic efficacy of medical management alone may be quite variable. This mode of therapy could possibly increase the efficacy of medical management of brain abscesses, especially in patients with multiple or surgically inaccessible brain abscesses.

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Cerebellar explants derived from neonatal mice were co-cultured with medulla containing inferior olive. The explants exhibited extracellular climbing fiber-like responses to electrical stimulation. On ultrastructural examination, many terminals with a high packing density of round, clear vesicles in a dark filamentous cytoplasm were present. Similar terminals, characteristic of climbing fibers, had not been identified in previous studies with cerebellar explants incorporating dorsal pons, but excluding medulla. The climbing fiber terminals formed appropriate synapses with Purkinje cell dendritic spines. The findings suggest that when climbing fibers are introduced into cerebellar cultures, accurate functional and morphological units are established.

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Granuloprival cerebellar cultures were transplanted after 9 or 16 days in vitro with cerebellar explants that had been exposed to kainic acid. The latter contained granule cells and differentiated glia, elements lacking in granuloprival cultures. Changes induced by transplantation observed by light microscopy included interposition of granule cells among the large cortical neurons of host explants; a reduction of the excess neurites of the Purkinje cell axon collateral system that is characteristic of granuloprival explants; and the appearance of myelinated fibers in previously unmyelinated cultures. The most notable electrophysiologic consequence of transplantation was the disappearance of inhibition of cortical spontaneous activity in response to antidromic stimulation of Purkinje cell axons, correlating with the disappearance of excess neurites, and suggesting that Purkinje cell recurrent collateral inhibition was no longer the dominant mode of cortical inhibition. Restoration of missing elements in granuloprival cultures incited development of structural and functional characteristics resembling those of normal cerebellar explants.

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Cytosine arabinoside-induced granuloprival cerebellar cultures lack both granule cells and differentiated glia and demonstrate marked synaptic reorganization. After kainic acid-exposed cerebellar explants, which contain granule cells and mature glia, were transplanted to the granuloprival cultures, the following ultrastructural features were noted: (1) parallel fibers formed normal synapses with Purkinje cell dendritic spines as well as with basket/stellate cell somata; (2) sprouted Purkinje cell recurrent axon collateral terminals were markedly reduced in number; (3) Purkinje cells matured and lost perisomatic spines; (4) astroglia formed sheaths around Purkinje cell somata and dendrites; and (5) axonal myelination occurred. The transplanted cultures demonstrated ultrastructural restitution toward normal after addition of missing elements.

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Phenytoin applied to developing neonatal mouse cerebellar cultures at concentrations of 9-46 micrograms/ml of nutrient medium from the day of explantation to 16 days in vitro induced cerebellar cortical degeneration. The degree of neurotoxicity correlated with drug concentration. Purkinje cells were the most susceptible of the cerebellar elements, and intracerebellar nucleus neurons were the most resistant. In contrast, mature mouse cerebellar explants were resistant to chronic exposure to high concentrations of phenytoin.

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Mature Purkinje cells in mouse cerebellar tissue cultures were morphologically analyzed by electron microscopy. Explants maintained for 19 to 31 days in vitro contained Purkinje cells that were similar in most respects to those described in vivo except for incomplete arborization of the dendritic trees. Typical features included (1) absence of Purkinje cell perisomatic spines; (2) a paucity of naked Purkinje cell dendritic spines; (3) a 1:1 relationship of Purkinje cell dendritic spines to parallel fiber terminals; and (4) almost complete astroglial investment of Purkinje cell somata and dendrites. Minimal extracellular space was present in the neuropil of the explants and unusual synapses involving Purkinje cells were absent. Atypical features described by some investigators may be a function of retarded development in suboptimal culture conditions and do not represent the limit of tissue culture methodology.

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Mouse-derived cerebellar explants were exposed for 5 days to cytosine arabinoside, an inhibitor of deoxyribonucleic acid synthesis. They were then maintained in normal nutrient medium until fixation for electron microscopy at 15-20 days in vitro. The cerebellar cortex lacked granule cells, but Purkinje cells, Golgi neurons and a few basket and stellate cells survived. Astrocytes and oligodendrocytes were diminished in number and myelination was absent. Purkinje cell recurrent axon collaterals increased in number and formed synapses with the surviving cortical neurons and their processes. The ultrastructural alterations that occurred in the cytosine arabinoside-treated cultures were consistent with an interpretation of cortical remodeling in which Purkinje cell axon collaterals were the dominant inhibitory elements.

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The finding of the acetylcholine synthetic enzyme, choline acetyltransferase, has been reported in mouse cerebellar cultures, and it has been used as an index of neuronal survival and maturation. These results are curious in light of immunocytochemical studies which show that this enzyme is localized within mossy fiber terminals in glomerular structures of the cerebellar cortex. Since most mossy fibers are of extracerebellar origin, a significant population of mossy fiber terminals would not be expected to be present in cerebellar cultures. The origin of this acetylcholine synthetic activity has been examined in mouse cerebellar cultures. Two groups of explants, one with and the other without incorporated dorsal pontine tissue, were cultivated. Only cultures that included pons showed well developed glomerular structures with mossy fiber rosettes. Homogenates of the cultures were assayed for their ability to synthesize acetylcholine, and the synthesis was shown to be due to choline acetyltransferase by use of the specific inhibitor, (naphthylvinyl)pyridine. Cultures lacking dorsal pontine tissue had only low levels of enzyme activity, whereas those which included pons had 20-60 times greater synthetic activity. These results indicate that the choline acetyltransferase activity arises from pontine tissue in cerebellar cultures and are consistent with mossy fibers being the source of this enzyme.

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Unmyelinated mouse cerebellar cerebellar cultures in which oligodendrocyte differentiation had been suppressed by exposure to cytosine arabinoside developed axonal myelin after superimposition of kainic acid-treated cerebellar explants devoid of myelin-receptive axons. The latter explants contained differentiated oligodendrocytes. The operation of a diffusible myelin-stimulating factor was ruled out by the failure of myelination in cytosine arabinoside-exposed explants not in direct contact with oligodendrocyte-containing transplants.

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