Gilbert H. Glaser

Violent Juvenile Delinquents: Psychiatric, Neurological, Psychological, and Abuse Factors

Abstract This study compares the neuropsychiatric, intellectual, and educational status of extremely violent and less violent incarcerated boys. The more violent children were more likely to demonstrate psychotic symptomatology (paranoid ideation and rambling, illogical associations) and to have major and minor neurological abnormalities. They were also more likely to have experienced and witnessed extreme physical abuse. The contribution of these factors to violent delinquency is discussed and implications for therapeutic intervention are suggested.

FAMILIAL ALZHEIMER'S DISEASE.

THE RECOGNITION of genetically determined causes for mental illness has received new interest recently.’ Furthermore, the increase in the number of older people in our population gives added interest to the pathologic states of the senium and presenium. Better nursing care and improved treatment of intercurrent infections have provided for the observation of the later states of many degenerative diseases. The progressive dementia syndromes in their early stages are difficult to differentiate from certain affective states.2 Still more difficult clinically is the differentiation between so-called Pick’s and Alzheimer’s disease. I t has long been thought3 that faniilial incidence would make Picks disease the more likely diagnosis. In many reports of Alzheimer’s disease, the family history is cited only briefly and suggestions of dementing illnesses in other members of the family are not fully explored. Nevertheless, since Alzheimer’s original description,4 heredity as an etiologic factor for this form of progressive dementia has been suggested many times in the world literature (table 1) . This investigation has dealt with the study of a family in which 11 members in 2 recent generations and 2 additional members in 2 past generations have been found to have signs and symptoms of a syndrome consisting of progressive mental deterioration, aphasia, seizures, myoclonus, immobile facies, plastic rigidity, and semiflexed posture. Histologic studies of the central nervous system in 4 of these cases provided evidence satisfying criteria for “Alzheimer’s disease.””*2F The features in each established case in this family were compared with the results of similar examinations of many presumably nonaffected relatives. In this way, possible early signs of Alzheimer’s disease or traits which might be associated with the disease were sought. An analysis of this sort is necessary to provide supporting evidence for the notion that a given disease process has a hereditary basis as well as providing information leading to early diagnosis or predictability of morbidity.

Hippocampal epileptic activity induced by localized ventricular perfusion with high-potassium cerebrospinal fluid

Abstract The effect of increasing K+ concentration in CSF on hippocampal neurons was studied by local perfusion of the inferior horn of the lateral ventricle of cats chronically prepared with implanted cannulae and electrodes. Localized paroxysmal discharge appeared from the perfused hippocampus after a latent period of 10–50 min when K+ in the perfusing CSF circulated at a rate of 0.81–1.62 μEq/min. The intensity of discharges was greater and the latent period shorter when K+ in CSF was increased from 8 mEq/liter to 16 mEq/liter. Single shocks delivered to dorsal hippocampus do not induce convulsive activity when K+ in CSF is normal, but induce convulsive activity when delivered during the “latent period” of a perfusion with high K+ CSF. The pattern of discharges suggested a primary action of K+ on basilar dendrites of hippocampal pyramidal cells. DC recording showed spike bursting superimposed on the repolarizing slope of a large negative slow wave indicating a possible disturbance of inhibitory phenomena.

A Review of Mouse Mutants as Genetic Models of Epilepsy

Summary: Here we review the major inherited convulsive disorders found in mice and discuss their possible relationship to specific clinical seizure disorders in humans. These mouse disorders include audiogenic seizures, the epilepsy (El) mutation, spontaneous seizures, the tottering/learner syndrome, cerebellar abnormalities, myelin disorders, and alcohol withdrawal seizures. Some of these disorders are symptomatic and others are idiopathic. We find that for many major types of epilepsy in humans there exists a similar counterpart in mice. Because the genetic constitution of the mouse is better known and more easily manipulated than that of other mammalian species, the mouse may serve as an excellent animal model for genetic and biochemical studies of epilepsy.

Cerebral, cerebellar, and brain stem gangliosides in mice susceptible to audiogenic seizures.

Abstract— The quantitative and qualitative distribution of gangliosides was investigated in the cerebrum, cerebellum and brain stem of audiogenic seizure resistant (C57BL/6J) and susceptible (DBA/2J) mice at 21 days of age. The concentration of gangliosides (μg/unit weight) was higher in the DBA cerebrum and brain stem, but lower in the DBA cerebellum compared to the concentration in C57 mice. In general, the brain water content was lower in DBA mice than in C57 mice. The distributions of a number of gangliosides were found to be different between the two strains and the differences were often in the same direction across the three brain regions. The most consistant and significant difference in ganglioside pattern observed between the strains was the higher concentration of GM1 in all three regions of the DBA brain. These results suggest that DBA mice have a more heavily myelinated CNS than C57 mice. The relationship of these observations to inherent audiogenic seizure susceptibility is discussed.

Socioeconomic Characteristics of Childhood Seizure Disorders in the New Haven Area: An Epidemiologic Study

Summary: An average of 66 cases of childhood epilepsy were diagnosed in a year in the New Haven Standard Metropolitan Statistical Area. The average annual incidence rate among those under age 15 was estimated to be 0.73 per 1,000, a rate consistent with those reported in other studies. These are the first U.S. data to report the incidence of epilepsy among black children. Blacks were found to be at much greater risk for childhood epilepsy than were whites. Estimates of annual incidence rates in the New Haven Standard Metropolitan Statistical Area were 1.36 per 1,000 for black males, 0.99 for black females, 0.63 for white males, and 0.60 for white females. The cumulative annual incidence rate of 11.03 per 1,000 suggested that 1 in 91 children in the New Haven Standard Metropolitan Statistical Area would suffer from epilepsy before their 15th birthday. Cumulative incidence rates were 19.63 per 1,000 for black males, 19.51 for black females, 9.53 for white males, and 9.10 for white females. During the later years of the decade, 1965–1970, there was an excess of epilepsy in black and white children living in lower socioeconomic areas. These findings were considered plausible, because low‐income groups tend to have high infant mortality rates, high rates of prematurity and birth defects, high accident rates, an excess of lead poisoning, and poor nutrition–factors known to contribute to the development of secondary epilepsy. Fifty‐four percent of cases of childhood seizures were diagnosed during the first 5 years of life. The mean age at diagnosis was slightly older for females than for males. Black and Spanish‐speaking children tended to be diagnosed at a somewhat earlier age than did white children. Among the 733 cases considered epileptic, there was a trend toward an excess of epilepsy among males.

DEVELOPMENTAL ASPECTS OF FOCAL EPILEPSIES OF CHILDHOOD TREATED BY NEUROSURGERY

Data on 50 patients treated surgically for intractable focal epilepsy were analysed. There were 10 hemispherectomies, 32 temporal lobectomies and eight operations to other areas of the brain. The median age at operation was 14 years. 29 patients were found to have mesial temporal sclerosis or sclerotic hemispheres and 17 had alien tissue and one sclerosis with heterotopia. No lesion was found in three cases. The nature of the first seizure was found to relate significantly to pathology. 30 patients had suffered an early convulsion. Between the convulsive insult and the onset of focal epilepsy there was a silent interval, the duration of which was biased by sex and side of lesion. The remaining 20 patients, of whom a highly significant number had alien tissue, had not had an early convulsion before the onset of focal epilepsy. The importance of accurate clinical histories is stressed. Clinical considerations alone predicted the pathology and laterality of the lesion in more than half the series. Regular EEG recordings and repeat scanning were found to be important investigations. Major disorders of behaviour had occurred in 44 patients. As adults, the series were free of severe psychiatric symptoms, but many required years of careful rehabilitation. 31 children had been excluded from normal schools before operation. Postoperatively, many patients continued their education in normal schools. Some required basic remedial teaching, others successfully undertook higher education and training. 49 patients benefited over‐all from neurosurgical treatment. 34 had no more habitual epilepsy at all. Full global gains often took at least five years to achieve.

Spontaneous polyspike discharges in an epileptic mutant mouse (tottering)

Abstract Electroencephalographic (EEG) recordings were made from unanesthetized, freely moving tottering mice. This neurological mutant exhibits spontaneous motor seizures. Although the intention of the present study was to determine an electrographic correlate of the motor seizures, no epileptiform discharge was found which was reliably associated with this type of ictal event. The present study revealed the occurrence of a paroxysmal pattern which appeared independently of the motor seizures. The polyspike pattern was a 6 s burst resembling the 3 s spike-wave complex often recorded in human epileptics. The waking behavior associated with the polyspiking in the tottering mice consisted of immobility and staring. In addition, polyspike bursts occurred during drowsiness. It is possible that the cerebellar defects found in tottering mice are related to their gait disturbance and to their motor seizures. The polyspike discharge appears to represent an independent ictal event, suggesting that tottering mice are susceptible to both motor and “absence” seizures. Previously documented examples of naturally occurring epilepsy consisted primarily of stimulus-evoked or “reflex” seizures. Tottering mice show promise for research of spontaneous, recurrent paroxysmal activity in a hereditary type of epilepsy.

Kindling induces a long-lasting change in the activity of a hippocampal membrane calmodulin-dependent protein kinase system

Septal kindling has been shown to produce a long-lasting decrease in endogenous calcium/calmodulin-dependent phosphorylation of hippocampal synaptic plasma membrane proteins, including two major bands of approximately 50,000 and 60,000 Daltons. These two proteins differ from the B-50 protein and tubulin, as evidenced by differences in migration in SDS-PAGE gels and by lack of cross-immunoreactivity with specific antibodies. Identity of these two proteins with the rho and sigma subunits of purified calmodulin-dependent kinase (CaM Kinase II) is suggested by similar migration in SDS-PAGE and two-dimensional gels, by similar calmodulin binding in two-dimensional gels, and similar 125I-peptide mapping of the 50,000 Dalton protein. These results demonstrate that septal kindling is associated with changes in the activity of a major Ca2+/calmodulin-dependent kinase system in hippocampal synaptic plasma membrane. This long-lasting modulation of kinase activity may provide a molecular insight into some aspects of neuronal plasticity.

Lipid and Protein Alterations of Spinal Cord and Cord Myelin of Multiple Sclerosis

Abstract: A comprehensive study was carried out to clarify the chemical compositions of spinal cord, cord myelin, and myelin subfractions of multiple sclerosis (MS). The protein compositions of normal‐appearing cerebral white matter and cerebral plaque and periplaque tissues were also analyzed for comparison. MS whole cord samples were found to contain higher amounts of water compared with normal samples. The total lipid contents were below normal. Among the individual lipids, cholesterol content remained unchanged, whereas cholesteryl esters appeared increased in MS cords. The acidic phospholipid concentrations were found to be lower than normal. Glycolipids, such as cerebrosides GM4, GM1, and GD1b, which are abundant in myelin, were all decreased. However, the concentrations of GM3 and GD3, which are more characteristic of reactive astrocytes, were highly elevated. The total protein content of MS cord samples was decreased, and the decrease was attributable to the loss of myelin proteins as evidenced by the low recovery of myelin. The concentrations of myelin‐specific proteins, such as proteolipid protein and myelin basic protein, were significantly reduced. Other changes in the protein compositions included the accretion of two low molecular weight proteins of approximately 11,000 and 12,000, and the appearance of a periodic acid‐Schiff‐positive protein with the same electrophoretic mobility as the P0 protein. Analysis of the isolated myelin indicated that it had a grossly normal protein composition. However, the two low molecular weight proteins and the P0 protein appeared to be enriched in an upper‐phase cord subtraction. We attribute the appearance of the two low molecular weight proteins to the breakdown of proteolipid protein and/or myelin basic protein as a result of demyelination, and the appearance of P0 to the involvement of PNS myelin. The latter finding provides the first biochemical evidence that in MS cord, remyelination can be achieved in part by invading Schwann cells and/or by the small number of Schwann cells that may be present in the cord.