Ad Hoc Meeting on A REAPPRAISAL OF ACTH THERAPY FOR INFANTILE SPASMS­WITH SPECIAL REFERENCE TO THE CT CHANGES DUE TO ACTH THERAPY-

Introduction Takehiko Okuno, MD Department of Pediatrics, Faculty of Medicine, Kyoto University, Kyoto

The location and severity of the central nervous sys­tem disorders due to variable etiologies have become easily visible since the introduction of cranial com­puted tomography, and the study of pediatric neuro­logical diseases has made a rapid progress.

We have observed a number of cases with infantile spasms in which CT scans showed cerebral atrophy (Okuno et al. Ann Paediatr Jpn 1978;24:46). About 75% of patients with infantile spasms showed vent­ricular and sulcal enlargement before ACm therapy. In our study (Okuno et al. J Comput Assist Tomogr 1980;4:20), chronic subdural effusion appeared to be a rare complication of ACm therapy. Cerebral atro­phy on CT scans was reversible in most patients at or over 1 month after ACm therapy stopped. However, in a part of patients, cerebral atrophy on CT scans was not reversible. Patients on ACm therapy should be carefully monitored.

Increased catabolism of proteins or sodium and water loss related to elevated glucocorticoids may explain the reversibility of cerebral atrophy with ACm therapy.

We hope that the abundant clinical experiences will be reported from the 4 institutes with lively dis­cussions.

Key words: ACTH therapy, infantile spasms, CT, brain atrophy.

152 Brain & Development, Vol 3, No 2,1981

Reevaluation of ACTH Therapy: Mainly CCT Findings of ACTH Therapy. Side Effects of ACTH Therapy Komei Kumagai, MD Department of Pediatrics, The Jikei University School of Medicine, Tokyo

For the purpose of reevaluation of ACm therapy for infantile spasms, we examined the side effects of ACm therapy in our patients with infantile spasms. Especially we checked easy infectious tendency, changes of serum electrolyte and CCT findings.

1) Severe infectious tendency was found in 8 of 12 cases after 1 to 2 months of ACm therapy.

2) Decreased serum P and increased serum Na were found in all 13 cases, in which electrolyte changes were examined during ACm therapy.

3) Pathological CCT [mdings, such as enlarged ventricles, dilated cerebral sulci, interhemispheric fis­sure and Sylvian cisterns, were found in all our 10 cases, which are treated by ACTH. Serially CCT and EEG were performed in one of our 10 cases. Marked brain atrophy was found after 6-week ACm therapy. However this atrophy improved on 2 months after ACm therapy had ended. It is usggested that these reversible changes seen on CCT scans represent a form of morphological plasticity of brain structures.

From the above results ACm therapy should be used carefuly at optimal dosages and periods.

Key words: ACTH therapy, infantile spasms.

Reversible Brain Shrinkage Following ACTH Treatment Hiroatsu Hojo, MD, Kenkichi Kataoka, MD, and Sho­zo Nakano, MD Department of Pediatric Neurology, Shizuoka Chil­dren 's Hospital, Shizuoka

Cranial computed tomography was examined before and after ACTII treatment in 29 cases of infantile spasms and 5 cases of Lennox-Gastaut syndrome. The age of patients ranged from 4 months to 5 years and 7 months. Mean follow-up period was 1 year and 3 months (2 months to 2 years and 4 months).

Ratio of the area of the sliced brain to the inner space of skull, measured with planimeter on apprarent­ly the largest slice on CT film, generally 2B and 3A section of EMI scan, was compared before and after treatment. Before treatment it showed 92.5% (±4.8), but at the end of continuous ACTH administration for 2 or 3 weeks it decreased to 87.5% (±5.4). It returned to the former value, 92.5% (±4.1) 4 to 6 months after the cessation of treatment. After that time, the ratio kept the same value throughout the observation period. The area of the sliced brain took a similar course, but this increased after 6 months due to natural brain growth. Width of the third ventricle, chosen as an index of ventricular dilatation, was 2.1 mm (±1.2) on CT film before treatment. It increased to 2.7 mm (±1.2) at the end of treatment, and returned to the former value 2.1 mm (±0.5) 4 to 6 months later as the brain skull ratio. Distance between the uncus, as an index of cisternal dilatation also took the same course.

These results mean that apparent brain atrophy on CT scan after ACTII treatment is reversible and return to the former figure by 6 month after cessation of treatment. Therefore it is better to use "shrinkage" instead of "atrophy." Brain shrinkage appears diffuse including cortical and subcortical structures.

Factors influence on the severity of brain shrinkage were also studied. The patients administered larger dose of ACTII showed more marked brain shrinkage than those on smaller dose. The younger group show­ed more marked shrinkage. We did not experience any case of subdural hematoma. This may be due to the fact that our patients were rather older comparing with reported cases.

Key words: Brain shrinkage, ACTH treatment, infan­tile spasms, Lennox-Gastaut syndrome.

Apparent Brain Atrophy and Subdural Hema­toma Following ACTH Therapy Kazuyoshi Watanabe, MD, Kimiko Hara, MD, Shuji Miyazaki, MD, and Susumu Hakamada, MD Department of Pediatrics, Nagoya University School of Medicine, Nagoya (KW); Division of Pediatric Neu­rology, Central Hospital, Aichi Prefectural Colony, Kasugai, Aichi (KH, SM, SH)

In 1977, we had a case of subdural hematoma which developed after ACTII therapy for infantile spasms, that prompted us to study systematically the relation­ship between ACTII treatment and apparent brain atrophy on the CT brain scan.

Case Report This severely retarded, quadriplegic infant developed infantile spasms with hypsarrhythmia at age 3 months, which were treated with clonazepam without success. The CT scan showed moderately enlarged ventricles at age 5 months. Daily intramuscular injection of 0.25 mg of synthetic ACTII-Z was administered 18 times from Oct. 4 through Oct. 29, without remark­able side effects. Seizures subsided with EEG improve­ment. There was no bulging of the fontanel nor increase of head circumference. She had no episode of head injury, nausea or vomitting. The CT scan on Nov. 22 revealed markedly enlarged subdural spaces, sug­gesting subdural hematoma. A subduro-atrial shunt was performed. The subdural hematoma was surround­ed by membranes and contained xanthochromic fluid with total protein of 2.2 gjdl and strongly positive Pandy and Nonne-Apelt reactions.

CT Scan before and after ACTH Therapy The CT scan was performed within 1 week before and after ACTH therapy in 12 cases of infantile spasms, 3 cases each of atonic seizure and Lennox syndrome.

Post-treatment CT scan demonstrated marked brain shrinkage in 3, moderate one in 6, slight one in 5 and minimal one in 4. The degree of apparent brain atrophy was not related to the etiology, clinical and electroencephalographic improvement or the degree of enlargement of subarachnoid spaces or ventricles be­fore ACTII therapy. Younger infants under 1 year of age tended to manifest more marked shrinkage than older children. Subarachnoid spaces of frontal and temporal lobes, Sylvian and interhemispheric fissures seemed to be more affected in infants and younger children, while ventricles and deep subarachnoid spaces did so in older children. The more ACTII was administered, the more brain shrinkage was observed in each patient, although the dose of ACTH which induced brain shrinkage was different in each patient. The degree of side effects of ACTII did not seem to be related to the extent of apparent atrophy. It was interesting that the change was minimal in two pa­tients who had been treated with V-P shunt for post­meningitic hydrocephalus. The CT fmdings returned to the pretreatment state nearly one month after the end of ACTH therapy.

Discussion One of the possible mechanisms for the subdural hematoma in our case might be the brain shrinkage induced by ACTII, which caused the brain to be pull­ed away from the dura with resulting stretch and rupture of the bridging veins. The disproportion be­tween the volume of the brain and the size of the skull might be another factor.

Conclusion Whatever the mechanisms of the apparent brain atro­phy or subdural hematoma following ACTII therapy, we should be cautious with long-term steroid or ACTII therapy especially in young infants.

Key words: ACTH, CT scan, infantile spasms, sub­dural hematoma, brain atrophy, brain shrinkage.

Brain & Development, Vol 3, No 2, 1981 153

Apparent Cerebral Atrophy on Computed Tomography in Nephrotic Children with Ster· oid Therapy and in Patients of Infantile Spasms with ACTH Therapy Eiji Yano, MD, Masashi Yamamoto, MD, Yukihiko Katafuchi, MD, Osamu Ishihara, MD, Toyojiro Matsu· ishi, MD, Nobuyuki Aoki, MD, and Fumio Yamashita, MD Department of Pediatrics and Child Health, Kurume University, School of Medicine, Kurume, Fukuoka (EY, YK, 01, TM, NA, FY); Department of Pediatrics, St. Mary's Hospital, Kurume, Fukuoka (MY)

To know the influence of steroid and ACTH on CNS, CSF·space/intracranial space ratio (%) (abbr.: C/I R) was calculated by computer processing of CT at the level of the 3rd and lateral ventricles in 16 cases of nephrotic patients on steroid, in 8 children with in· fantile spasms on ACTH, and in 34 controls. Steroid (prednisolone) and ACTH·Z were administered in doses of 60 mg/SA/day (daily) for 4 weeks, and

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0.25 mg/day (daily) for 2-3 weeks, respectively. Twelve of 16 nephrotic patients treated with ster·

oid revealed abnormally high C/I R compared with controls (C/I R revealed 1.6 ± 0.8% in controls, 5.7 ± 3.8% in nephrotic children). Nine of 12 cases with abo normally high C/I R showed normal C/I R after the withdrawal of steroid (Fig 1). Abnormal neurologic and psychiatric symptoms were found in 8 of 16 cases (manic state in 2, depressive state in 1, muscle weak· ness in 4 and tremor of fingers in 1). The presence of the above was not correlated with the grade of C/I R.

In 7 of 8 children with infantile spasms, C/I R reo vealed 5.1 ± 3.9% before ACTH therapy and 16.9 ± 8.2% at the completion of ACTH therapy. However, C/I R measured at the average follow·up period of 14.2 (± 4.9) months (except 1 case with 2 months) showed the same range of C/I R before the therapy (Fig 2). The above data suggested that steroid and ACTH could cause reversible cerebral atrophic changes as demonstrated by the increase of C/I R.

Fig 1 Sequential changes in CSF-space/ intracranial space (%) by YHP.computer analyzing after withdrawal of steroid administration in 12 nephrotic patients.

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154 Brain & Development, Vol 3, No 2,1981