J.R. Stevens

A comparison of the psychological test performance of patients with focal and nonfocal epilepsy

Abstract In this investigation psychological tests were used to study the performance of patients with various forms of epilepsy. A pilot study suggested that patients with temporal lobe epilepsy perform more poorly than patients with centrencephalic or diffuse epilepsy on a test of memory and that the reverse might be true on a test of attention. The memory and attention test were therefore administered to a larger, independent sample of epileptic patients which consisted of two groups with focal epilepsy (39 cases with temporal lobe and 18 with frontal lobe foci) and one group with nonfocal epilepsy (19 cases of whom 14 were of the centrencephalic variety). The several groups were matched by statistical means to control for differences in intelligence, age, duration of illness, seizure frequency, and amount of EEG abnormality. When analyzed in this manner, the results support the preliminary finding that the nonfocal (centrencephalic) patients perform more poorly than the focal patients on the test of attention; there were, however, no significant differences among groups on the memory test. Possible reasons for the inconsistent results on the memory test are discussed. The impairment of the nonfocal (centrencephalic) patient on the attention test is interpreted in terms of the Penfield and Jasper hypothesis of subcortical dysfunction in this disease.

Cerebral transplants for seizures: preliminary results.

Summary: Several critical brain regions have been identified in which application of γ‐aminobutyric acid (GABA) potentiating agents in small quantities can suppress or prevent generalized and kindled amygdala seizures, i.e., substantia nigra and deep prepiriform cortex. Severity of audiogenic seizures in the genetically epilepsy prone rat (GEPR) is reduced by injection of norepinephrine (NE) into the lateral ventricles and by GABA in inferior colliculus. The present investigation examines the potential for raising epileptic thresholds by increasing local GABAergic or NE inhibitory activity by means of brain transplants of tissue rich in GABA or NE neurons. Two models of epilepsy were used: amygdala‐kindled seizures and sound‐induced seizures in GEPRs. Transplantation of embryonic cerebellar or cortical tissue to the deep prepiriform area of amygdala kindled rats transiently raised seizure thresholds in three of the nine animals. Transplantation of embryonic cerebellar or cortical tissue to the inferior colliculus or adrenal medulla tissue to lateral ventricles of GEPRs did not appreciably reduce the intensity of audiogenic seizures in these animals.

The expression of phosphorylated neurofilament epitopes in human brains.

The expression of phosphorylated neurofilaments (PNF) epitopes in hippocampal neurons was examined in 5 cases of Alzheimers disease and 12 brains of schizophrenic patients. A control group (n = 17) consisted of 5 brains of patients with other acute or chronic neurologic disorders and 12 brains of persons who were free of any known neurologic disease. Immunocytochemistry with monoclonal antibodies to PNF was done on formalin-fixed, paraffin sections of hippocampus. Adjacent sections were impregnated with silver. Immunoreactivity to PNF was observed in tangles and plaques of the Alzheimers brains and also in hippocampal pyramidal cells in 6 of the 12 schizophrenic brains and in 9 of the 17 control brains (2 with neurological disorders and 7 with non-neurological diseases). The positive PNF-stained cell bodies, in silver impregnated sections, generally did not show evident neurofibrillary abnormalities. Enzymatic dephosphorylation prior to immunostaining abolished PNF reactivity. These results suggest the widespread occurrence and relative non-specificity of perikaryonal PNF immunoreactivity in human post mortem brain tissue. We could not exclude the possibility that the hippocampal and brainstem neurons are predilection sites for normal perikaryonal phosphorylation in human brain.

Abstract 34. Inoculation of schizophrenic brains to rodents and primates: behavioral and neuropathological observations

33. Transmission studies of neurological and psychiatric disease in the marmoset R.M. Ridley, H.F. Baker, T.J. Crow, A.J. Cross, G.W. Roberts, G.R. Taylor Division of Psychiatry, Clinical Research Centre, Harrow, U.K. and L.W. Duchen Institute of Neurology, Queen Square, London, U.K. The behaviour of 6 marmosets (Callithrix jacchus) inoculated intracerebrally with CSF from schizophrenic patients was compared over a 23 year period with the behaviour of marmosets inoculated with CSF from patients with neurodegenerative disease or from patients undergoing spinal anaesthesia who suffered from no neurological or psychiatric disorders. Animals inoculated with CSF from psychiatric or neurological patients became progressively and significantly less active than animals inoculated with CSF from other patients although, post-mortem, no consistent differences between groups of animals were found in light or electron-microscopic brain examination, brain biochemical analysis or viral isolation. In another experiment all 4 marmosets inoculated intracerebrally with brain material from a patient with the Gerstmann-Str~ussler syndrome (G.S.S.) developed a spongiform encephatopathy which was indistinguishable from that shown by another 4 marmosets inoculated with brain material from a typical case of Creutzfeldt-Jakob disease in a comparable time course of 20-32 months. The familial occurrence of a viral disease in G.S.S. will be discussed. Abstract 34. Inoculation of schizophrenic brains to rodents and primates: behavioral and neuropathological observations D.R. Weinberger, C.A. Kaufmann, J.R. Stevens, D.M. Asher, J.E. Kleinman, J.E. Parisi, J. Langloss and C.J. Gibbs, Jr. Section on Clinical Neuropsychiatry and Neurobehavior, Adult Psychiatry Branch, NIMH, Saint Elizabeths Hospital, Washington, D.C., U.S.A.34. Inoculation of schizophrenic brains to rodents and primates: behavioral and neuropathological observations D.R. Weinberger, C.A. Kaufmann, J.R. Stevens, D.M. Asher, J.E. Kleinman, J.E. Parisi, J. Langloss and C.J. Gibbs, Jr. Section on Clinical Neuropsychiatry and Neurobehavior, Adult Psychiatry Branch, NIMH, Saint Elizabeths Hospital, Washington, D.C., U.S.A. To test the possibility that schizophrenia might result from a transmissable agent analogous to the CJD agent, homogenized brain from various cortical and subcortical regions of 10 patients with chronic schizophrenia was inoculated intracerebrally into 37 primates and 22 rodents. No gross behavioral peculiarities were noted in routine observations by veterinarians and animal technicians over a five year follow-up period. One squirrel monkey and one guinea pig developed ataxia and tremor at 44 and 20 months respectively. Reinoculation with original innoculum has been negative at 40 months. Nineteen rodents and 11 primates died during the follow-up period. Histopathological examination of rodent brains showed cerebellar and hippocampal gliotic changes in 5/9 experimental cases and 3/9 controls. Similar findings were not observed in primate brains which could not be differentiated from controls. schizophrenia analogous While these results do not support a transmissable agent model for to CJD, it is not conclusive evidence against a virus as certain known viral illnesses also cannot be transmitted (e.g. SSPE). Abstract 35. Coronavirus infection in rats: brain antigen induction of an autoimmune response against35. Coronavirus infection in rats: brain antigen induction of an autoimmune response against H. Wege, R. Watanabe, R. DCtrries, P. Massa and V. ter Meulen Institute for Virology and Immunobiology, W~rzburg, West Germany