Jean Holowach

THE EFFECTS OF ANOXIA UPON ENERGY SOURCES AND SELECTED METABOLIC INTERMEDIATES IN THE BRAINS OF FISH, FROG AND TURTLE

The levels of the main cerebral energy reserves, ATP, P‐creatine, glycogen and glucose, and of several glycolytic intermediates and lactate, were measured in the brains of fish (Carassius auratus), turtle (Pseudemys scripta elegans) and frog (Rana pipiens). The levels of glycogen in these brains were 2‐9 times higher than those reported for mammals. In frog, cerebral glycogen levels were 35 per cent higher during the winter than in spring. The P‐creatine: ATP ratios were 3 instead of the more usual (mammalian) value of 1. The levels of other intermediates were similar to those found in mammalian brain.

Psychomotor seizures in childhood. A clinical study of 120 cases.

Summary One hundred and twenty cases of psychomotor epilepsy in children have been reviewed. 1. Eleven per cent of 1,054 pediatric patients with epilepsy had psychomotor attacks. In our experience psychomotor epilepsy is twice as common as the petit mal type. 2. Clinically, the cases could be divided broadly into 5 types of behavior: arrest of activity, masticatory, automatic, psychic, and vertiginous. 3. Fifty-five children had a family history of convulsions; parents or siblings were affected in 23. 4. Thirty per cent had an age at onset of 3 years or less. This is half the percentage of that seen in 1,054 cases of all types of epilepsy in childhood. 5. One third of the children had an obvious background of organicity. The etiological significance of previous convulsions, particularly febrile seizures, is emphasized. 6. The majority of cases were misdiagnosed as petit mal seizures. Hysteria, behavior disorder, nightmares, and fabrication must also be ruled out. 7. One fourth of those in the series were mentally deficient children as determined of those in the tested group exhibited behavior disorders. 8. Of 117 electroencephalograms, only 17 were normal or indeterminate. 9. About one third of the patients with psychomotor epilepsy were completely controlled, another third were not controlled, and one third were inadequately followed for proper evaluation. Acetazolamide as an adjuvant to previous therapy is recommended in intractable cases.

Infantile myoclonic seizures:An evaluation of ACTH and corticosteroid therapy

Summary The results of corticosteroid and corticotropintherapy of infantile myoclonic seizures as recorded in the literature have been reviewed and 24 additional cases are presented. Of 283 infants (259 reported in medicalliterature; 24 in the series recorded here), complete seizure control was achieved in 34 per cent and another 28 per cent showed significant improvement. Factors pertaining to the success or failure of therapy are discussed. Despite the gloomy ultimate prognosis of infantile myoclonic seizures at the present stage of our understanding of the syndrome, the immediate salutary effects of corticotropin on seizure frequency and on improvement of the EEG in a significant number of children appear to warrant its trial in every infant with this very serious disorder.

A clinical evaluation of acetazolamide (diamox) in the treatment of epilepsy in children.

Summary Fifty-six patients with epilepsy refractory to standard anticonvulsive therapy were treated with Diamox. Seizures were completely controlled in 62.5 per cent (35 cases); 16 per cent (9 cases) were improved well over 50 per cent; 21.4 per cent (12 cases) were unchanged. Despite the tendency for development of tolerance, the prompt control of many cases of epilepsy of diverse types with few side effects makes Diamox a valuable drug in the clinical management of epilepsy.

Recognition and investigation of hypoglycemia.

F R o 1~ our experience with children with hypoglycemia during the past 35 years, we have come to feel that the disease is often not recognized before considerable brain damage has occurred. Early positive diagnosis and understanding of the etiology of hypoglycemia demand a high index of suspicion, proper laboratory evaluation, and a methodical plan of study. Suspicion of its possibility should be aroused both by the clinical picture and by circumstances judged favorable to its development, even in the absence of clearcut signs or symptoms. The latter is especially true of newborn or very young infants and of children who have had many episodes of hypoglycemia and who seem to have acquired some tolerance for it. The clinical picture seems dependent on quite a number of factors, such as age, duration of the hypoglycemia, its etiology,

Jacksonian seizures in infancy and childhood

Summary One-hundred and fourteen cases of jacksonian epilepsy in infants and children are reviewed. Incidence .—The reported frequency of local motor seizures, 7.5 per cent is probably too low because of failure of observation from onset or rapid spread of epileptic discharge. Sex .—Both sexes were about equally affected. Race .—The ratio of Negro to white patients was considerably below the hospital average. Age At Onset .—The greatest incidence was among infants and young children with a progressive decline toward adolescence. Forty-eight per cent were less then 3 years of age. It seems logical to implicate pre-, peri-, and postnatal factors in etiology. A delayed onset of organic epilepsy was usual. Heredity .—Twenty-eight per cent of 95 cases had a history of epilepsy in close relatives (half in parents or siblings). This confirms Lennoxs impression of the influence of heredity in organic epilepsy in children. Etiology .—Cause was known in only 34 per cent of cases. Almost two thirds were related to birth injury (13 cases) or congenital or infantile hemiplegia (11 cases). Eleven patients had postnatal acquired disease of the central nervous system of varied etiology. Diffuse surface hemangiomata were demonstrated in 2 cases. Only one patient had an expanding intracranial lesion. The latter also had severe birth injury with hemiplegia and extensive cortical sclerosis. Cerebral neoplasm is a relatively rare cause of jacksonian epilepsy in infants and children. Seizure Analysis .—There was no right or left predominance of jacksonian phenomena. One third had bilateral spread. The commonest site of origin was the face or hand. Only 9 of 60 cases began in the leg. Abnormal sensation prior to movement was common. Nocturnal attacks were fairly frequent. Six patients had febrile seizures before the onset of jacksonian epilepsy. In 4 these were of great frequency. The interval between the febrile and jacksonian seizures was over 2 years in 5 of the 6 cases. One half of this group had a family history of epilepsy. Occasionally, circumstances suggested that jacksonian epilepsy might be a residual of local brain damage from severe and protracted seizures with high fever. In another 6 cases, early jacksonian seizures occurred only with fever and infection. The presence of severe neurological abnormalities prior to the onset of seizures in 3 of these cases confirms the impression that fever and infection can trigger a latent tendency for jacksonian epilepsy. Twenty-five patients had other types of seizures. Five had grand mal epilepsy prior to the onset of local seizures. Five with organic brain involvement had “atypical” petit mal (myoclonic or akinetic). In 4, these preceded the onset of jacksonian epilepsy. Fifteen patients had recurrent paroxysmal phenomena compatible with epileptic discharge without motor component. Hemiplegia .—Twenty-seven patients (23.6 per cent) had hemiplegia. The majority were attributable to prenatal factors or birth injury. Forty-eight per cent were mentally retarded. Postepileptiform paralysis (Todd and Robertson) of varied duration was common. With frequently recurring or prolonged seizures such paralysis may be progressive and ultimately permanent. This was the case in at least 10 patients in our series. This course of events attests to the need for prompt control of jacksonian seizures. Mental Retardation .—Twenty-eight patients (24 per cent) were mentally retarded prior to onset of jacksonian epilepsy. Etiological factors were evident in two thirds. Four patients appeared to develop mental retardation consequent to severe recurrent seizures. Serious behavior disorder was a chief complaint in 4 children. The Electroencephalogram .—In general, the conformance of focal electroencephalogram findings with inferences drawn from pattern of seizure is good, even when only a single tracing is available. An expected electrographic focus is more likely to be demonstrated in a child than in an infant. Spike foci are nonspecific indicators of a region of high cortical excitabity, and not necessarily of underlying structural abnormality. Slow wave foci, recorded with or without accompanying focal spike discharges, more frequently presage proof of underlying structural disorder. Of the 83 children in the series who had electroencephalograms, 18 had neurological lateralizing signs. In 12 of these, a focal process was recorded in the expected locale. In the remaining 65 cases without neurological abnormality, 19 showed focal spike processes in the suspected hemisphere and in 6 others the focus was paradoxical. Fifteen showed generalized spiking. Seven showed slow focal patterns over the central region of the suspected hemisphere. One tracing was normal and the remainder showed intermediate or markedly slow resting frequencies without focalization. Air Encephalograms .—Close observation of patients with local seizures is essential. Encephalography is not routine. Criteria for air studies are increased intracranial pressure, neurological abnormalities or failure of response to adequate antiepileptic therapy. One half of the encephalograms made were considered abnormal. Recognized cause for these abnormalities was present in only 13 of 24 cases. Ten of the 24 patients with abnormal air studies were retarded mentally. Arteriograms were sometimes abnormal with normal pneumoencephalograms and vice versa.

Chronic lymphoid leucemia in children

Summary Chronic lymphoid leucemia in children was reviewed briefly with thesuggestion that the cases reported were probably acute leucemia with a somewhat longer course than usual. Detailed observations were given on a 3 1/2-year-old girl who had had a very large, firm spleen since early infancy and who had a persisting hyperleucocytosis, the majority of the cells being small mature lymphocytes. There was no thrombocytopenia or hemorrhagic diatheses. The bone marrow showed a marked lymphocytic infiltration. In spite of the fact that there was no general enlargement of the lymph nodes, it was felt that this child had sufficiently characteristic findings to classify the case as one of chronic lymphoid leucemia.

Effects of various anions and cations on the release of four dehydrogenases from brain mitochondria by a non-ionic detergent.

Summary It has been found that a number of agents greatly affects the release by Triton-X-ioo of certain dehydrogenases from rabbit-brain mitochondria. The enzymes studied were DPN-dependent isocitrate dehydrogenase ( L s-isocitrate:DPN+ oxidoreductase (decarboxylating), EC 1.1.1.41) and TPN-dependent isocitrate dehydrogenase ( L s-isocitrate:TPN+ oxidoreductase (decarboxylating), EC 1.1.1.42), gluta-mate dehydrogenase ( L -glutamate:DPN+ (TPN+) oxidoreductase (deaminating), EC 1.4.1.3) and lipoamide dehydrogenase (DPNH:lipoamide oxidoreductase, EC 1.6.4.3). The effects of Triton X-100 on the morphology of the mitochondria were checked with the electron microscope. 1. The detergent was shown to disrupt the architecture of the mitochondria, leaving single and double membranes and amorphous material. 2. ATP, ADP, pyrophosphate, citrate and isocitrate enhanced release of the enzymes. DPN was less effective, and α-ketoglutarate, adenylic acid and adenosine were ineffective, as was EDTA. 3. K+ and Na+ (80 mM) enhanced release of both isocitrate dehydrogenases, but partially prevented release of glutamate dehydrogenase. Ca2+ and Mg2+ at 4–5 mM enhanced release of TPN-isocitrate dehydrogenase but inhibited that of DPN-isocitrate dehydrogenase and glutamate dehydrogenase. Mg2+ had little effect on the release of lipoamide dehydrogenase. 4. It is suggested that metal ions play a role in the binding of these four dehydrogenases to the mitochondria, but that the details of the attachments may be different in each case.