Thomas E. Zion

Double-blind study of ACTH vs prednisone therapy in infantile spasms.

Twenty-four patients with infantile spasms were entered in a double-blind, placebo-controlled, crossover study to compare the therapeutic effectiveness of ACTH (20 to 30 units/day) with that of prednisone (2 mg/kg/day). Response to therapy was determined by utilizing a comprehensive monitoring system and was defined as a complete cessation of spasms and disappearance of the hypsarrhythmic EEG pattern. A major difference between the effectiveness of ACTH and that of prednisone in stopping the spasms and improving the EEG pattern was not demonstrated. Nine patients responded to ACTH (five initial drug, four crossover), and seven patients responded to prednisone (four initial drug, three crossover). Twelve responded within two weeks of initiation of therapy, and four within six weeks. Therapy was tapered and discontinued immediately after a response was obtained. Five patients had a relapse; four responded rapidly to a second course of therapy. Of the eight patients who failed to respond to hormonal therapy, seven were given clonazepam with no improvement.

Prospective study of outcome of infants with infantile spasms treated during controlled studies of ACTH and prednisone

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.

Congenital rubella encephalitis: Course and early sequelae†

Neurological abnormalities were noted at some time between birth and 18 months of age in 81 of 100 patients with congenital rubella infection. These included lethargy, full fontanel, irritability, and increased concentration of protein and persistence of virus in the cerebrospinal fluid. Of the 64 survivors 44 had a wide range of neurological abnormalities at 18 months of age including motor paresis, restlessness, motor mannerisms, and developmental delay. Retardation in growth, particularly of the head, was still manifest at 18 months. Pathological changes in central nervous system structures included leptomeningitis, vasculitis, and multifocal areas of parenchymal necrosis and perivascular calcification.

A controlled study of ACTH therapy in infantile spasms.

Summary: A controlled study of 5 patients with infantile spasms was performed to détérmine the effectiveness of corticotropin (ACTH) treatment. Patients were monitored serially, using a time‐synchronized polygraphic and video system. Serum Cortisol levels were détérmined by radioimmunoassay. Four patients showed total cessation of seizures and normalization of the EEG on low‐dose ACTH therapy. Two of these patients became hypertensive, requiring discontinuance of ACTH. Serum Cortisol levels increased markedly in all patients after initiation of ACTH therapy. There appeared to be no consistent difference in serum Cortisol levels between patients receiving 20 units/day of ACTH and those receiving 30 or 40 units/day, and there was no difference in Cortisol levels in those patients who became hypertensive and those who did not.

Quantitative Analysis and Characterization of Infantile Spasms

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‐oculo‐gram, 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.

A Controlled Study of Prednisone Therapy in Infantile Spasms

Summary: 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.

The longitudinal course of congenital rubellaencephalitis in nonretarded children

The neurologic course of congenital rubella syndrome was traced in 29 nonretarded children to 9 to 12 years. During the first two years, manifestations involved abnormal tone and reflexes (69%), motor delays (66%), feeding difficulties (48%), and abnormal clinical behavior (45%). Hearing loss was documented in 76%. From three to seven years, poor balance, motor incoordination (69%), and behavioral disturbances (66%) predominated. Hearing losses increased to 86%. Currently, at 9 to 12 years, 25 have residua which include learning deficits (52%), behavioral disturbances (48%), poor balance (61%), muscle weakness (54%), and deficits in tactile perception (41%). Two additional children now have hearing loss. The encephalitic manifestations of congenital rubella syndrome are diverse. Overriding problems differ at each phase of childhood. Current deficits influence progress in educational and home environments. For these children, adequate intelligence alone does not guarantee academic success.

Long‐Term Prognosis of Patients with Infantile Spasms Following ACTH Therapy

Summary: 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.

Computed tomography in infantile spasms: Effects of hormonal therapy

During a prospective double-blind, crossover study of ACTH versus prednisone therapy, serial computed tomography (CT) scans were performed on 16 children with infantile spasms. Pre-treatment scans revealed four findings: normal (6 patients), generalized atrophy (bilaterally enlarged ventricles and/or subarachnoid space) (2 patients), predominantly focal atrophy (3 patients), and congenital anomalies (5 patients). Within 2 weeks of initiating relatively low therapeutic dosages of ACTH or prednisone, a significant number of the infants (63%) had CT findings consistent with decreased cortical volume; in many cases (44%), these findings had not reversed 4 to 6 weeks after discontinuing therapy. Duration of therapy did not correlate significantly with the persistence of CT changes.