Surgical treatment for infantile spasms?
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Biomedical subjects
Publications and source records attributed to P Kellaway.
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We report the long-term outcome of 64 infants with infantile spasms, followed prospectively, using controlled treatment schedules and objective techniques (24-hour EEG and video monitoring) to determine response. Average age at follow-up was 50 months. Of the 64 infants, three (5%) died; of the others, 41 (67%) had developmental retardation of 50% or more or an IQ of 50 or less. Eight patients (13%) composed our cryptogenic study group and were so classified on the basis of normal CT scan, normal development prior to onset of infantile spasms, and undetermined cause. These patients had the better outcome; 38% had normal development or were only mildly retarded. Both the responders and nonresponders in our symptomatic group had a poor outcome; only 5% had normal development or mild impairment. Outcome was not significantly influenced by short versus long treatment lag or by response to therapy. Other types of seizures occurred in 34 patients (53%). In summary, the overall prognosis for long-term outcome in these 64 patients with infantile spasms was poor.
With the use of a time-synchronized video and polygraphic recording system, 5,042 infantile spasms were monitored and analyzed in 24 infants aged 1 to 43 months. Of these, 33.9% were flexor, 22.5% extensor, and 42.0% mixed flexor-extensor. Sometimes the spasms were followed by a period of akinesia and diminished responsiveness lasting up to 90 seconds, and rarely (1.0%) this "arrest" effect constituted the entire seizures. More than one type of seizure occurred in 21 of the 24 infants. In the same number, 78.3% of the seizures occurred in clusters, and the intensity and frequency of the spasms in each cluster often increased to a peak, then progressively decreased until they stopped. Predominantly, the clusters occurred soon after arousal from sleep. The number of seizures occurring at night (55.2%) was similar to the diurnal number (44.8%). The electroencephalographic seizure pattern was variable, but a marked generalized attenuation of electrical activity was a feature of 71.7% of the attacks. Attenuation episodes of similar degree and duration occurred with no evidence of a seizure.
The influence of ACTH on the prognosis of patients with infantile spasms remains controversial. We have examined retrospectively the long-term benefits of initially successful ACTH therapy in patients treated at this institution between 1961 and 1974. Individuals with equivocal or minimal improvement during ACTH therapy were excluded from this study. Eighteen affected infants showed a favorable early response consisting of cessation of seizures for at least 3 weeks during ACTH therapy and concurrent disappearance of the hypsarhythmic EEG pattern. Modal age at last follow-up was 5 years (range, 15 months to 16 years). Infantile spasms recurred in 7 patients (39%), and 8 patients subsequently had other seizure types. All epileptiform (spike) activity disappeared from the EEGs of 8 patients during ACTH therapy, but in 4 of these cases epileptiform activity was present in later tracings. In the remaining 10 patients the hypsarhythmic pattern disappeared in association with ACTH therapy, but the EEG remained epileptiform (often only in sleep). Later EEGs were free of epileptiform activity in 5 of the 10 patients whose tracings contained spike discharges in the early follow-up period. Four patients (22%) were seizure free and without intellectual impairment when last evaluated.
A controlled study of 12 patients with infantile spasms was performed to determine the effectiveness of prednisone treatment. Patients were monitored serially, using a time-synchronized polygraphic and video system. Three patients (25%) showed prompt reduction in seizure frequency and normalization of the EEG after institution of treatment. The remaining patients showed no improvement in seizure frequency or significant change in the EEG.
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An effective, time-synchronized monitoring system for the study of patients with infantile spasms has been developed. This system utilizes concurrent graphically recorded data, including EEG, body movement via triaxial accelerometry, respiration, electrocardiogram, electromyogram, electro-oculogram, and galvanic skin response. These data, when evaluated in conjunction with a closed-circuit TV recording of the patient, greatly facilitate the differentiation of seizures from nonictal activity and permit the characterization and quantification of the behavioral, motor, and autonomic phenomena intrinsically associated with infantile spasms.
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We measured the concentrations of phenobarbital, phenytoin, primidone, ethosuximide, antipyrine, and caffeine in paired samples of saliva and plasma by gas chromatograph-mass spectrometer-computer (GC/MS/COM) and enzyme immunoassay. Mixed saliva was collected for the antipyrine and caffeine studies, parotid saliva for the phenobarbital, primidone, ethosuximide and phenytoin studies. The saliva/plasma (S/P) ratios (by weight) obtained by GC/MS/COM were: phenobarbital, 0.31-0.37; phenytoin, 0.11; ethosuximide, 1.04; antipyrine, 0.83-0.95; caffeine, 0.55. The S/P ratio obtained by enzyme immunoassay were: phenobarbital, 0.32; phenytoin, 0.12; primidone, 0.85. The concentrations of phenytoin, primidone, ethosuximide and antipyrine in saliva correspond to the free fraction of the drug in plasma. When we analyzed samples containing phenobarbital or phenytoin (plasma or saliva) by both techniques, we found that the enzyme immunoassay values were generally higher than GC/MS/COM values, suggesting that the metabolites as well as the parent drug were measured in the immunoassay.
The effects of cerebellar stimulation were studied in monkeys with chronic alumina-cream epileptogenic foci in motor cortex. Low-frequency stimulation (5-15 c/sec) was ineffective in altering spontaneous cortical spiking. Clinical and electrographic seizures were elicited following high-frequency cerebellar stimulation (100 c/sec). This was a consistent finding following cerebellar stimulation, although no spontaneous seizures had been seen in these animals. These studies suggest the existence of facilitatory cerebellar mechanisms and indicate the need for further studies in chronic animal models.
In two groups of purebred juvenile Hampshire pigs, left anterior descending coronary occluders were implanted. The pigs were then adapted to the recording chamber until they would manifest a criterion pattern of sleep while in it. In group A, permanent coronary artery occlusions were produced, and the effects of various sleep stages on the resultant cardiac arrhythmias were observed. Sleep intervals during which transitional and slow wave (SW) sleep alternated were correlated with increased arrhythmias relative to the awake state (P less than 0.04). The increase was maximum during sustained periods of SW sleep. Intervals during which rapid eye movement (REM) sleep predominated were correlated with a reduction in arrhythmias. In group B, temporary occlusions were made during both an awake condition and after criterion patterns of either SW or REM sleep. Occlusions after SW sleep reduced the ventricular fibrillation latency compared with that during the awake control state (P less than 0.05), whereas occlusions after REM sleep increased ventricular fibrillation latency (P less than 0.05). We conclude that SW SLEEP, BUT NOT REM sleep, has a deleterious effect on the ischemic myocardium. REM sleep may have a beneficial effect, since it increases ventricular fibrillation latency. Heart rate changes do not appear to be correlated with the effects of either sleep stage.
The evaluation and outcome of 22 patients who had onset of complex partial seizures (CPS) of temporal lobe origin in childhood and subsequently underwent anterior temporal lobectomy are described. All patients showed improved seizure control; 81.8% had a reduction greater than or equal to 95% in seizure frequency. However, many patients had difficulty adjusting to a seizure-free life. Psychosocial, behavioral, and educational problems occurred more frequently in patients whose surgery was delayed until adult life. We conclude that attempts should be made early in the course of CPS of childhood to determine whether the seizures are truly intractable to medical management so that surgical intervention can be expedited.