Edward F. Rabe

The effect of ACTH therapy upon infantile spasms

Fifty-five infants with infantile spasms and hypsarrhythmia, who were treated with ACTH using 80 units im every other day for a mean period of ten months, were studied retrospectively and showed better results than infants using so-called nonsteroidal anticonvulsants or ACTH and steroids in other doses and with other time intervals. The study showed that the treatment with ACTH within the first month of onset of spasms produced a higher incidence of spasm-free state while on treatment, a shorter duration of spasms while on treatment, and a higher incidence of spasm-free state while on treatment, a shorter duration of spasms while on treatment, and a higher incidence of a spasm-free state when off treatment, compared to a similar regimen of ACTH begun after seizures had persusted for more than a month. The value of early treatment of infantile spasms suggests that the treatment of this disease should be regarded as a medical emergency.

The value of neuroradiology in infantile spasms

The results of neuroradiologic studies of 71 children with infantile spasms treated with ACTH were correlated with the developmental outcome at follow-up (mean 62 months, range 14 to 207 months). Fifty-two (73%) patients had an abnormal NRS on initial evaluation; 49% had cerebral atrophy, 18% had congenital anomalies, and 6% had hydrocephalus. Twenty patients were normal on initial clinical evaluation. At follow-up only the eight (40%) with normal NRS were normal. Twelve (60%) who had unexpected abnormalities on NRS were retarded at follow-up. CAT scanning is necessary to predict the developmental outcome in developmentally normal children with infantile spasm. Eight of nine patients with normal NRS in the early treatment group were developmentally normal at presentation and follow-up. Ten patients who were developmentally normal before spasms began, and had normal NRS but were in the late treatment group, were retarded at initial evaluation and follow-up. This finding suggests that early treatment of children who have a normal NRS and normal development at onset of spasm prevents mental retardation.

Cystic lesions of the posterior fossa in infants A comparison of the clinical, radiological, and pathological findings in Dandy‐Walker syndrome and extra‐axial cysts

AN IhlPOHTAiYT PART of the neurological examination of infants is skull transillumination. A specific pattern of abnormal transillumination in the posterior fossa has been described in the Dandy-Walker syndr0me.l-4 Recently, two infants were seen with abnormal posterior fossa traiisillumination unlike that seen with the Dandy-Walker syndrome. Posterior fossa extraaxial cysts (PFEAC) were demonstrated by angiography and air contrast studies and confirmed by surgical exploration. T h e purpose of this paper is to describe and correlate the pattern of skull transillumination, neuroradiological features, gross and microscopic pathology, and certain clinical features of these two patients with PFEAC and to compare these features with similar ones in two children with the Dandy-Walker syndrome.5-7 The similarities and dissimilarities in the pathogenesis of these two conditions also will be discussed.

THE HYPOTONIC INFANT. A REVIEW.

Summary (Table I) I. The factors concerned in maintainingnormal muscle tone have been described in detail as a background to the understanding of the possible sites of pathology which can lead to hypotonia. II. The causes of hypotonia in childrenunder 24 months of age have been discussed from the point of view of the presumed site of pathology. The classification which has evolved from this approach is as follows: A. Hypotonia due to diseases of thecentral nervous system: 1. Atonic diplegia 2. Congenital chorea and athetosis 3. Congenital cerebellar ataxia 4. Kernicterus 5. Mongolism 6. Tay-Sachs diseas B. Hypotonia due to diseases of thespinal cord: 1. Werdnig-Hoffmans disease (infantileprogressive muscular atrophy) 2. Myelopathic arthrogryposis multiplexcongenita 3. Congenital anterior poliomyelitis C. Hypotonia due to diseases of thespinal roots or peripheral nerves: 1. Acute and chronic polyneuropathy D. Hypotonia due to abnormalities of the myoneural junction: 1. Congenital myasthenia gravis 2. Neonatal (transient) myasthenia gravis E. Hypotonia due to diseases of themuscle: 1. Benign congenital hypotonia 2. Universal muscular hypoplasia 3. Congenital infantile muscular dystrophy with or without arthrogryposis multiplex congenita 4. Dystrophica myotonica 5. Central core disease 6. Rod body myopathy 7. Polymyositis 8. Glycogen storage disease III. The value of ancillary aids in thediagnosis of the etiology of hypotonia in infants has been discussed. These have included muscle biopsy, electromyography, measurement of the nerve conduction time, determination of serum enzyme concentrations, urinary creatine and creatinine excretion coefficients, and the assessment of the developmental level of the infant.

1156 INFANTILE SPASMS: EVALUATION OF A STANDARDIZED TREATMENT REGIMEN

Infantile spasms have been considered refractory seizures carrying a poor prognosis for seizure control and intellectual devlopment. Treatment with conventional anticonvulsants, ACTH and corticosteroids, as well as newer agents such as nitrazepam, diazepam and clonazepam have produced variable results for seizure control, but they have all been associated with extremely high recurrence rates. Therefore, they have not been shown to alter the natural history of this seizure disorder.This study presents an analysis of a standardized treatment regimen using ACTH in treating infantile spasms. Data is presented relating to each patients neurologic status and seizure incidence on treatment and after a prolonged period of follow-up averaging 50 months. Fifty-five patients initially received ACTH, 40 units qd while hospitalized, followed by 80 units qod for a minimum of 3 months at home. The dosage was maintained at this level while improvement was being shown in seizure frequency and EEG pattern. ACTH was then tapered slowly. Thirty-one patients were treated within 1 month (GpI) and 24 patients more than 1 month after seizure onset (GpII). Complete seizure control of 87% of GpI patients and 56% of GpII patients (P<0.05) was achieved on ACTH. The recurrence rate was 3.2% for GpI and 12.5% for GpII patients. The seizure control rate for GpI surpasses previously reported studies in which recurrence rate of 33-67% have resulted in overall seizure control rates of only 15-40%. Our results substantiate the use of early and prolonged high dose ACTH therapy for infantile spasms.

Two Types of Congenital Cysts of the Posterior Fossa: A Comparison of Their Clinical and Pathological Characteristics and Their Embryogenesis

Two types of cystic lesions can occur in the posterior fossa of infants and children. In one type there is a cystic dilatation of the 4th ventricle known as the Dandy-Walker (D-W) syndrome, and in the second type, a cyst or cysts overlie the cerebellum. This is referred to as a posterior fossa extra-axial cyst (PFEAC). These two entries may be differentiated clincally as will be illustrated by presentation of the findings in 2 infants with PFEAC and 2 with D-W syndrome. The pattern of skull transillumination is distinctive for each entity, although the differences are subtle, and can enable the clinician to suspect the correct diagnosis immediately. Arteriographic and air contrast findings show silmilar abnormalities in the supratentorial region in both conditions but distinctive differernces are present in the infratentorial from that in D-W syndrome. Inferences drawn from a comparsion of the arteriographic and histologic findings in these 4 cases with the appearance of certain brain structures at different stages of human embryogenesis indicate that both conditions are congenital abnormalities occuring before the 3rd fetal month but affecting the leptomeninages in one instance (PFEAC) and the cerebellar anlage in the other (D-W syndrome).