Don L. Thurston

Prognosis in childhood epilepsy: additional follow-up of 148 children 15 to 23 years after withdrawal of anticonvulsant therapy.

To evaluate the risk of relapse in children with epilepsy whose anticonvulsant therapy has been withdrawn after prolonged control, we studied 148 such children for 15 to 23 years or until relapse. Forty-one of the 148 patients (28 per cent) had recurrence of seizures; of these, 35 (85 per cent) had relapses within five years of drug withdrawal. Factors associated with an increased risk of relapse were a long duration of epilepsy before control, neurologic dysfunction, and jacksonian seizures or combinations of seizure types. We found no association between risk of recurrence and age at onset of epilepsy, total number of seizures before control, age at discontinuation of therapy, electroencephalographic abnormalities, or family history of epilepsy. We conclude that children who do not have the additional risk factors noted above have an excellent chance of remaining seizure free after the withdrawal of anticonvulsant drugs.

The late effects of lead poisoning.

Summary Eleven cases of lead intoxication have been followed for a period of from five to ten years with repeat physical, psychological, and laboratory examinations. The physical sequelae consisted of blindness and cerebral dysrhythmia Sodium citrate was the specific therapy in all cases and was given over a variable period of time or until there was no laboratory evidence of lead intoxication. There is no evidence in this series of continuing mental deterioration. Considering the major mode of instruction in the primary grades, it is felt that these children are at a serious disadvantage and should receive special attention to offset their visualmotor deficit. As the child matures there is a gradual loss of the inward driven hyperactive behavior frequently seen in brain-damaged children. There is no direct correlation between the severity of the illness and the amount of residual effect. Pediatric counseling might be influential in reducing a parenteral overprotective attitude which adds to the childs problems.

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.

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.

Mode of action of streptomycin in relation to thechanges in spinal fluid sugar in tuberculous meningitis: II. Observations on the effect of intrathecal streptomycin treatment on the cerebrospinal fluid sugar in tuberculous meningitis

Summary 1. Case histories and spinal fluid sugars are reviewed in five patients having tuberculous meningitis: a. Case 1, B. P., had a block at the region of the fourth ventricle. This patient did not have previous I.T. streptomycin therapy. b. Case 2, D. L., had a history of tuberculous meningitis of one months duration. As in Case 1, there had been no prior treatment with streptomycin intrathecally. c. Case 3, L. S.; Case 4, M. M.; and Case 5, C. M.—all had previous therapy with I.T. and parenteral streptomycin up to the test period. 2. In the two cases, B. P. and D. L.,not having previous I.T. or parenteral streptomycin therapy, variable increases in the C.S.F. sugar were noted at intervals up to eighteen hours after treatment. 3. In Case M. M. after I.T. streptomycin had been discontinued for a four-week period and then larger amounts given (0.1 Gm. instead of 0.05 Gm.), there was a marked increase in the C.S.F. sugar. 4. In Case C. M. it was noted that there was a gradual rise in C.S.F. sugar eighteen days after I.T. and parenteral therapy were instituted. This did not correlate with clinical improvement because, as noted, the C.S.F. sugar remained elevated (within normal range) despite actual clinical deterioration and death. 5. In two cases, L. S. and C. M.,after previous treatment with I.T. and subcutaneous streptomycin, there was very little rise noted in the C.S.F. sugar twelve to twenty-four hours after intrathecal streptomycin therapy. 6. Evidence is presented that streptomycins action as a nonglucose reducing substance is not responsible for the rise in spinal fluid sugar after intrathecal treatment with this antibiotic. a. In Case B. P., the rise of C.S.F. sugar occurred five hours (Fig. 2) after the peak of streptomycin concentration in the C.S.F. This increase, being “true” sugar, would indicate that streptomycins effect as a nonglucose reducing agent is not the cause of the increased spinal fluid sugar. b. Increases in the C.S.F. glucose inCases B. P., M. M., and D. L., during the test periods were demonstrated to have been due to “true” sugar. In Case L. S., pretreatment levels of C.S.F. sugar and those during the test period were all near the low level of 10.7 mg. per 100 ml. In Case C. M., however, the levels prior to and during the test period were normal.

Mode of action of streptomycin in relation to thechanges in spinal fluid sugar in tuberculous meningitis: III. A theory of the mode of action of streptomycin in vivowith a commentary on the current literature

Summary A theory on the mode of action ofstreptomycin in tuberculous meningitis is presented that explains the rise of C.S.F. sugar after treatment with streptomycin. The hypothesis is formulated to correlate known clinical observations and laboratory data: Streptomycin in the injured cell in tuberculous meningitis causes inhibition of carbohydrate metabolism. The increase in spinal fluid sugar noted after the initial treatment with streptomycin is secondary to decreased utilization of glucose by the living cell and unimpaired flow of spinal fluid.

Prognosis in childhood epilepsy: A follow-up study of 148 cases in which therapy had been suspended after prolonged anticonvulsant control

One hundred and forty-eight unselected epileptic children, seizure-free for 4 years on anticonvulsant medication, were followed for 5 to 12 years after drug withdrawal to determine the frequency of seizure recurrence and to discern any prognostic criteria. Thirty-six children (24%) had a recurrence of seizures. Sixty-one per cent of recurrences took place during the first year of gradual discontinuation of therapy. Drug withdrawal at puberty (9–15 yrs) was not associated with increased risk. An analysis of the records revealed no relation of relapse to sex, race, heredity, or seizure frequency. The prognosis was very good in children who had an early age of onset with prompt control (relapse rate 13%). There was at least a two-fold increase in relapse in cases with a late onset, with prolonged duration of seizures, and evidence of neurologic, psychologic, and electroencephalographic abnormalities. The most striking correlate to relapse was seizure type.Best results were obtained in children with grand mal (relapse rate 8%), febrile seizures (12%), and uncomplicated petit mal (12%). In psychomotor attacks the relapse rate was 25%. The highest recurrence was in children with Jacksonian seizures (53%) and those who had seizures of more than one type (40%). It was concluded that these data suggest unquestionable criteria for drug withdrawal in epileptic children after prolonged seizure control with a favorable outcome in a large percentage of selected cases.

Asterol; further search for neurological disturbances.

In a preliminary report 1 we described our findings in 39 children who had received topical applications of Asterol (2-dimethylamino-6 [β-diethylaminoethoxy] -benzothiazole) dihydrochloride for the treatment of tinea capitis. Pertinent to this subject was the high incidence (38%) of abnormalities in the pretreatment EEGs of these patients. Two children developed hallucinations during therapy, and three others showed electroencephalographic changes only. Reapplication of Asterol in polyethylene glycol (Carbowax) to four of these patients for prolonged periods of time failed to reproduce these findings. We have extended our search for neurologic disturbances, and it is the purpose of the present communication to describe and review our experience with a total of 151 children, who were observed for signs of neurotoxicity associated with the administration of Asterol. All of the patients in this study were obtained from the tinea-capitis clinic at this hospital. The patients were divided into two groups as follows: The