- Email: [email protected]
Computed tomography in infantile spasms: Effects of hormonal therapy
Computed Tomography in Infantile Spasms: Effects of Hormonal Therapy D a n i e l G. Glaze, MD*t, Richard A. Hrachovy, biD*, J a m e s D . Frost, Jr, MD*,
Thomas E. Z i o n , M D t , R. Nick Bryan, MD, PhD*
During a prospective double-bfind, 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 fmdings 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. Glaze DG, Hrachovy RA, Frost Jr, JD, Zion TE, Bryan RN. Computed tomography in infantile spasms: Effects of hormonal therapy. Pediatr Neurol 1986;2:23-7.
prospective double-blind, crossover study of ACTH versus prednisone therapy.
Methods Sixteen infants, age 31/2 to 24 months (median age, 8 months), who were determined by clinical and electroencephalographic (EEG) examination to be experiencing infantile spasms, were studied. Each infant had continuous polygraphic/EEG/video monitoring for 24 hours before treatment and then periodically during treatment; the infantile spasms were precisely characterized and quantified by previously described techniques [4,5]. After the initial 24-hour monitoring session, an infant was begun on either ACTH (20 units/day), or prednisone (2 mg/kg/day), and a placebo. If a response did not occur within 2 weeks, the dosage of ACTH was increased to 30 units/day. Head circumference (OFC) was measured before initiation of therapy and at the time of each CT. All patients had an initial CT before treatment, a second CT 2 weeks after initiation of treatment, and a third CT 4-6 weeks after completion of all therapy (maximum of 6 weeks of ACTH, 30 units/day, and maximum of 6 weeks of prednisone, 2 mg/kg/day). The CTs were evaluated by a neuroradiologist and a pediatric neurologist who were unaware of the specific treatments, changes in the electroencephalograms, and seizure frequencies of each patient. The CTs were evaluated specifically for enlargement of the ventricles and/or subarachnoid space.
Introduction Infantile spasms are an age-specific convulsive disorder of infancy and early childhood. Treatment with ACTH or corticosteroids is considered to be the only effective therapy. Enlargement of the ventricles and subarachnoid space has been seen with computed tomography (CT) after treatment with ACTH or corticosteroids [1-3]. These changes reportedly are transient and disappear after cessation of therapy [2,3]. The rate at which these changes appear after initiating hormonal therapy and disappear after its discontinuance, however, has not been well documented. We report the results of CT evaluation of 16 patients with infantile spasms who were examined during a
Results Table 1 summarizes the pre-treatment CT findings in relationship to hormonal therapy and to the development and persistence of brain shrinkage. Normal pre-treatment CTs were seen in 37 % (6 / 16) of the patients. In 63 %, CTs were abnormal and showed the following: generalized atrophy (bilaterally enlarged ventricles and/or subarachnoid space) in 13 % (2 / 16); predominantly focal atrophy in 19% (3/16); and congenital anomalies (lissencephaly, calcium deposits, tuberous sclerosis, or agenesis of the corpus caUosum and enlarged ventricles) in 31% (5/16). A second CT 2 weeks after initiation of therapy revealed that 63%
From the *Section of Neurophysiology, Department of Neurology; tSection of Pediatric Neurology, Department of Pediatrics; and ~Section of Neuroradiology, Department of Radiology~ Baylor College of Medicine and The Methodist Hospital; Houston, Texas
Dr. Glaze; Section of Neurophysiology, Department of Neurology; Baylor College of Medicine; One Baylor Plaza; Houston, TX 77030. Received September 2, 1985; accepted December 10, 1985
Communications should be addressed to:
Glaze et al: Therapy of Infantile Spasms
23
B
C
Figure 1. Patient III-11. CT (A) pre-treatment, (B) a#er 2 weeks of tberapy, and (C)posttreatment, demonstrating development of brain shrinkage without subsequent resolution. 24
PEDIATRIC NEUROLOGY
Vol. 2 No~ 1
Table 1. Summaryof results Pn:sence of Shrinkage
Patient No.
Age (Months)
Response to Therapy
Duration of Therapy (wk)
Pre-treatment CT Findings?
CT during TL~atment*
CT 4-6 weeks Post-t~atment
(Drug)
Il1-9
9
Yes
8
N
Yes (Prednisone)
No
III-10
7
Yes
8
F
Yes (Prednisone)
No
III-11
4
No
8
N
Yes (ACTH)
Yes
III- 12
13
Yes
8
N
Yes (ACTH)
Yes
Ill-13
6
No
12
F
No (Prednisone)
No
III-14
8
Yes
6
C
No (Prednisone)
No
III- 15
8
Yes
2
N
Yes (Prednisone)
No
III-16
51/2
Yes
2
F
Yes (ACTH)
No
III-17
5 l/z
Yes
14
N
No (ACTH)
Yes
III- 18
11
Yes
8
N
No (ACTH)
Yes
III-19
5
Yes
6
C
No (Prednisone)
Yes
III-20
4
Yes
12
C
Yes (Prednisone)
Yes
III-21
7
Yes
2
C
Yes (ACTH)
No
III-22
7
No
8
C
Yes (ACTH)
No
III-23
10
No
12
G
No (Preclnisone)
No
III-24
10
No
12
G
Yes (Prednisone)
Yes
~N = normal; F = focal atrophy; C = congential anomalies; G = generalized atrophy *Drug in use for two weeks at time of CT
(10/16) of these patients had developed mild to moderate enlargement of the ventricles and/or subarachnoid space, although the OFC had not changed significantly in any of the 16. Of the 10 patients whose second CT registered changes, 5 had received ACTH and 5 had received prednisone initially. There was no clinical response to therapy in 40 % (4/10) of the patients who had changes on the second CT and in 33% (2/6) of those who did not have changes on the second CT. In 44% (7/16), the third CT demonstrated enlargement of the ventricles and/or subarachnoid space (Fig 1A,B,C). These changes also had been seen
onthe second CT in 4 patients (1II-10, 11, 20, and 24), 2 of whom responded to therapy. These changes were seen for the first time in the other 3 (III-17, 18, 19), all of whom responded to therapy. Of these 7, 4 had normal CTs initially. Although the 2 oldest infants (11 and 13 months) had persistence of cerebral shrinkage, the age ranges were similar to those developing this change (4-13 months) versus those not (6-10 months) and for those with persistence of effect (4-10 months) versus those without persistence (51/2-10 months). Duration of therapy did not correlate significantly with persistence of CT changes.
Glaze et al: Therapy oflnfantile Spasms
25
Discussion In this study, the pre-treatment CT was abnormal in a significant number of patients (63 %). This result is comparable to previously reported findings [6,7]. As emphasized by Gastaut et al. [6], the highly varied nature and distribution of the CT abnormalities indicate that the underlying lesions are not directly responsible for the infantile spasms or hypsarrhythmia. An increase in subarachnoid space and ventricular size on CT has been reported after hormonal treatment of infantile spasms [1-3,8,9]. During those studies, changes occurred in patients treated with reasonably high dosages of ACTH (80-120 units/day) and for relatively prolonged periods (5-10 weeks) [2,3]. In our study, we documented that those CT changes occurred in a significant number of patients (63 %) after only 2 weeks of relatively low dosages of ACTH or prednisone. There was no correlation between these changes and etiology, response to therapy, or age. The findings of Hara et al. [1] support these results. In previous studies [1-3,8], these changes appeared to be reversible. In our study, however, at 4 to 6 weeks after cessation of ACTH or prednisone therapy, 7 patients continued to exhibit these changes without any appreciable reversal of the initial CT. The initial CT had been normal in 4 of the 7 patients. The persistence of ventricular enlargement or subarachnoid space enlargement did not correlate with a larger cumulative dosage of ACTH or prednisone. Serial CTs in untreated patients with infantile spasms have not been reported. It is highly unlikely, however, that the CT changes we observed were the result of the disease's natural history. The 6 patients with treatment lags of 7 to 19 months did not have generalized enlargement of the ventricles or subarachnoid space prior to initiation of hormonal therapy. Increases in subarachnoid space or ventricles appeared rapidly and occurred in 10 patients within 2 weeks after initiation of hormonal therapy. In 9 of 16 patients, these CT changes did not persist after hormonal therapy was withdrawn. In 2 patients who did not respond to hormonal therapy, the CT changes either did not occur or did not persist after withdrawal of hormonal therapy (Table 1, Patients III-13 and III-22). Several explanations have been suggested for the changes that occur on CT during hormonal therapy of infantile spasms; these include communicating hydrocephalus, loss of water, alterations in the bloodbrain barrier, and inhibition of brain growth [1-3,810]. Lyen et al. [9] offered two alternative interpretations of the CT changes. First, pre-trearment 26
PEDIATRIC NEUROLOGY
Vol. 2 No. 1
CT scans may represent "cerebral swelling" superimposed upon underlying cerebral atrophy that is "unmasked" by hormonal therapy. Generalized cerebral atrophy, however, is not an invariable finding on CT or at autopsy. In our series, only 2 of 16 patients had this CT finding. In addition, the CT changes may represent communicating hydrocephalus secondary to alterations of the circulatory dynamics of CSF by ACTH. Carollo et al. [8] performed CTs before, during (3 weeks), and after ACTH treatment (1 week to 1 year) in 8 patients with infantile spasms. All patients demonstrated changes (widening of the sulci, cisterns, and ventricles) after 3 weeks of therapy. In 2 patients, intracranial pressure monitoring registered higher than normal values, with a return to normal after cessation of ACTH and in association with the disappearance of the CT abnormality. The authors suggested that these results support the hypothesis of an evolving, communicating hydrocephalus. The methodology of intracranial pressure monitoring was not presented, and maximum intracranial pressures were reported for only 2 patients; pre- and post-treatment values were not presented. In addition, OFCs were not reported. Increases in these infants' OFCs might be expected if communicating hydrocephalus is associated with distension of the subarachnoid space and enlargement of the ventricles. In our patients, there were no significant changes in the OFC, although changes were observed on CT. Siemes et al. [10] studied the pre- and post-treatment CSF in 20 children with infantile spasms. The CSF protein pattern was abnormal and consistent with increased cerebrovascular permeability for proteins, especially for albumin, but did not document increased gamma globulin, which is present in acute or chronic central nervous system infections. After 2-3 weeks of ACTH therapy, the CSF protein pattern normalized. The authors suggested that the changes in CT and CSF could be explained partially by reduction of cerebral swelling. CT findings and their correlation with the CSF changes were not presented in that report. Their findings are at some variance with the findings and suggestions of Lyen et al. [9[ and Carollo et al. [8], since an evolving, communicating hydrocephalus would be expected to be associated with abnormal blood-brain barrier function and CSF absorption. The persistence of CT changes in 44 % of our patients 4 to 6 weeks after discontinuance of hormonal therapy suggests that these changes were probably not secondary to water shifts or to a communicating hydrocephalus.
The pathophysiology of hormone-induced CT changes in infants with infantile spasms remains unknown. Since these changes occur even with relatively low dosages and short durations of therapy and may persist for weeks after discontinuance of hormonal therapy, further investigation of the clinical and biochemical effects of ACTH and prednisone is warranted. This work was supported by grant NS 11535 from the National Institute of Neurological and Communicative Disorders and Stroke, NIH. References [1] Ham K, Watanabe K, Miyazaki S, et al. Apparent brain atrophy and subdural hematoma following ACTH therapy. Brain Dev 1981;3:45-9. [2] Lagenstein I, Willig RP, Kuhne D. Cranial computerized tomography (CCT) findings in children treated with ACTH and dexamethasone: First results. Neuropaediatrie 1979;10:370-84.
[3] Maekawa K, Ohta H, Tamai I. Transient brain shrinkage in infantile spasms after ACTH treatment. Report of two cases. Neuropediarrics 1980; 11:80-4. [4] Frost JD Jr, Hrachovy RA, Kellaway P, et al. Quantitative analysis and characterization of infantile spasms. Epilepsia 1978;19:273-82. 151 Kellaway P, Hrachovy RA, Frost JD Jr, et ai. Precise characterization and quantification of infantile spasms. Ann Neurol 1979;6:214-8. [6] Gastaut H, Gastaut JL, Regis H, et al. Computerized tomography in the study of West's syndrome. Dev Med Child Neurol 1978;20:21-7. [7] Singer WE), Hailer JS, Sullivan LR, et ai. The value of neuroradiology in infantile spasms. J Pediatr 1982; 100;47-50. [8] Carollo C, Marin G, Scanarini M, et al. CT and ACI'H treatment in infantile spasms. Childs Brain 1982;9:347-53. [9] LyenKR, Holland IM, Lyen YC. Reversible cerebral atrophy in infantile spasms caused by corticotropin. Lancet 1979;2:237-8. [10] Siemes H, Rating D, Hanefeld F. Infantile spasms: CSF proteins before and during treatment with ACTH. Dev Med Child Neurol 1981;23:384.
Glaze et al: Therapy of Infantile Spasms
27
Thomas E. Z i o n , M D t , R. Nick Bryan, MD, PhD*
During a prospective double-bfind, 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 fmdings 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. Glaze DG, Hrachovy RA, Frost Jr, JD, Zion TE, Bryan RN. Computed tomography in infantile spasms: Effects of hormonal therapy. Pediatr Neurol 1986;2:23-7.
prospective double-blind, crossover study of ACTH versus prednisone therapy.
Methods Sixteen infants, age 31/2 to 24 months (median age, 8 months), who were determined by clinical and electroencephalographic (EEG) examination to be experiencing infantile spasms, were studied. Each infant had continuous polygraphic/EEG/video monitoring for 24 hours before treatment and then periodically during treatment; the infantile spasms were precisely characterized and quantified by previously described techniques [4,5]. After the initial 24-hour monitoring session, an infant was begun on either ACTH (20 units/day), or prednisone (2 mg/kg/day), and a placebo. If a response did not occur within 2 weeks, the dosage of ACTH was increased to 30 units/day. Head circumference (OFC) was measured before initiation of therapy and at the time of each CT. All patients had an initial CT before treatment, a second CT 2 weeks after initiation of treatment, and a third CT 4-6 weeks after completion of all therapy (maximum of 6 weeks of ACTH, 30 units/day, and maximum of 6 weeks of prednisone, 2 mg/kg/day). The CTs were evaluated by a neuroradiologist and a pediatric neurologist who were unaware of the specific treatments, changes in the electroencephalograms, and seizure frequencies of each patient. The CTs were evaluated specifically for enlargement of the ventricles and/or subarachnoid space.
Introduction Infantile spasms are an age-specific convulsive disorder of infancy and early childhood. Treatment with ACTH or corticosteroids is considered to be the only effective therapy. Enlargement of the ventricles and subarachnoid space has been seen with computed tomography (CT) after treatment with ACTH or corticosteroids [1-3]. These changes reportedly are transient and disappear after cessation of therapy [2,3]. The rate at which these changes appear after initiating hormonal therapy and disappear after its discontinuance, however, has not been well documented. We report the results of CT evaluation of 16 patients with infantile spasms who were examined during a
Results Table 1 summarizes the pre-treatment CT findings in relationship to hormonal therapy and to the development and persistence of brain shrinkage. Normal pre-treatment CTs were seen in 37 % (6 / 16) of the patients. In 63 %, CTs were abnormal and showed the following: generalized atrophy (bilaterally enlarged ventricles and/or subarachnoid space) in 13 % (2 / 16); predominantly focal atrophy in 19% (3/16); and congenital anomalies (lissencephaly, calcium deposits, tuberous sclerosis, or agenesis of the corpus caUosum and enlarged ventricles) in 31% (5/16). A second CT 2 weeks after initiation of therapy revealed that 63%
From the *Section of Neurophysiology, Department of Neurology; tSection of Pediatric Neurology, Department of Pediatrics; and ~Section of Neuroradiology, Department of Radiology~ Baylor College of Medicine and The Methodist Hospital; Houston, Texas
Dr. Glaze; Section of Neurophysiology, Department of Neurology; Baylor College of Medicine; One Baylor Plaza; Houston, TX 77030. Received September 2, 1985; accepted December 10, 1985
Communications should be addressed to:
Glaze et al: Therapy of Infantile Spasms
23
B
C
Figure 1. Patient III-11. CT (A) pre-treatment, (B) a#er 2 weeks of tberapy, and (C)posttreatment, demonstrating development of brain shrinkage without subsequent resolution. 24
PEDIATRIC NEUROLOGY
Vol. 2 No~ 1
Table 1. Summaryof results Pn:sence of Shrinkage
Patient No.
Age (Months)
Response to Therapy
Duration of Therapy (wk)
Pre-treatment CT Findings?
CT during TL~atment*
CT 4-6 weeks Post-t~atment
(Drug)
Il1-9
9
Yes
8
N
Yes (Prednisone)
No
III-10
7
Yes
8
F
Yes (Prednisone)
No
III-11
4
No
8
N
Yes (ACTH)
Yes
III- 12
13
Yes
8
N
Yes (ACTH)
Yes
Ill-13
6
No
12
F
No (Prednisone)
No
III-14
8
Yes
6
C
No (Prednisone)
No
III- 15
8
Yes
2
N
Yes (Prednisone)
No
III-16
51/2
Yes
2
F
Yes (ACTH)
No
III-17
5 l/z
Yes
14
N
No (ACTH)
Yes
III- 18
11
Yes
8
N
No (ACTH)
Yes
III-19
5
Yes
6
C
No (Prednisone)
Yes
III-20
4
Yes
12
C
Yes (Prednisone)
Yes
III-21
7
Yes
2
C
Yes (ACTH)
No
III-22
7
No
8
C
Yes (ACTH)
No
III-23
10
No
12
G
No (Preclnisone)
No
III-24
10
No
12
G
Yes (Prednisone)
Yes
~N = normal; F = focal atrophy; C = congential anomalies; G = generalized atrophy *Drug in use for two weeks at time of CT
(10/16) of these patients had developed mild to moderate enlargement of the ventricles and/or subarachnoid space, although the OFC had not changed significantly in any of the 16. Of the 10 patients whose second CT registered changes, 5 had received ACTH and 5 had received prednisone initially. There was no clinical response to therapy in 40 % (4/10) of the patients who had changes on the second CT and in 33% (2/6) of those who did not have changes on the second CT. In 44% (7/16), the third CT demonstrated enlargement of the ventricles and/or subarachnoid space (Fig 1A,B,C). These changes also had been seen
onthe second CT in 4 patients (1II-10, 11, 20, and 24), 2 of whom responded to therapy. These changes were seen for the first time in the other 3 (III-17, 18, 19), all of whom responded to therapy. Of these 7, 4 had normal CTs initially. Although the 2 oldest infants (11 and 13 months) had persistence of cerebral shrinkage, the age ranges were similar to those developing this change (4-13 months) versus those not (6-10 months) and for those with persistence of effect (4-10 months) versus those without persistence (51/2-10 months). Duration of therapy did not correlate significantly with persistence of CT changes.
Glaze et al: Therapy oflnfantile Spasms
25
Discussion In this study, the pre-treatment CT was abnormal in a significant number of patients (63 %). This result is comparable to previously reported findings [6,7]. As emphasized by Gastaut et al. [6], the highly varied nature and distribution of the CT abnormalities indicate that the underlying lesions are not directly responsible for the infantile spasms or hypsarrhythmia. An increase in subarachnoid space and ventricular size on CT has been reported after hormonal treatment of infantile spasms [1-3,8,9]. During those studies, changes occurred in patients treated with reasonably high dosages of ACTH (80-120 units/day) and for relatively prolonged periods (5-10 weeks) [2,3]. In our study, we documented that those CT changes occurred in a significant number of patients (63 %) after only 2 weeks of relatively low dosages of ACTH or prednisone. There was no correlation between these changes and etiology, response to therapy, or age. The findings of Hara et al. [1] support these results. In previous studies [1-3,8], these changes appeared to be reversible. In our study, however, at 4 to 6 weeks after cessation of ACTH or prednisone therapy, 7 patients continued to exhibit these changes without any appreciable reversal of the initial CT. The initial CT had been normal in 4 of the 7 patients. The persistence of ventricular enlargement or subarachnoid space enlargement did not correlate with a larger cumulative dosage of ACTH or prednisone. Serial CTs in untreated patients with infantile spasms have not been reported. It is highly unlikely, however, that the CT changes we observed were the result of the disease's natural history. The 6 patients with treatment lags of 7 to 19 months did not have generalized enlargement of the ventricles or subarachnoid space prior to initiation of hormonal therapy. Increases in subarachnoid space or ventricles appeared rapidly and occurred in 10 patients within 2 weeks after initiation of hormonal therapy. In 9 of 16 patients, these CT changes did not persist after hormonal therapy was withdrawn. In 2 patients who did not respond to hormonal therapy, the CT changes either did not occur or did not persist after withdrawal of hormonal therapy (Table 1, Patients III-13 and III-22). Several explanations have been suggested for the changes that occur on CT during hormonal therapy of infantile spasms; these include communicating hydrocephalus, loss of water, alterations in the bloodbrain barrier, and inhibition of brain growth [1-3,810]. Lyen et al. [9] offered two alternative interpretations of the CT changes. First, pre-trearment 26
PEDIATRIC NEUROLOGY
Vol. 2 No. 1
CT scans may represent "cerebral swelling" superimposed upon underlying cerebral atrophy that is "unmasked" by hormonal therapy. Generalized cerebral atrophy, however, is not an invariable finding on CT or at autopsy. In our series, only 2 of 16 patients had this CT finding. In addition, the CT changes may represent communicating hydrocephalus secondary to alterations of the circulatory dynamics of CSF by ACTH. Carollo et al. [8] performed CTs before, during (3 weeks), and after ACTH treatment (1 week to 1 year) in 8 patients with infantile spasms. All patients demonstrated changes (widening of the sulci, cisterns, and ventricles) after 3 weeks of therapy. In 2 patients, intracranial pressure monitoring registered higher than normal values, with a return to normal after cessation of ACTH and in association with the disappearance of the CT abnormality. The authors suggested that these results support the hypothesis of an evolving, communicating hydrocephalus. The methodology of intracranial pressure monitoring was not presented, and maximum intracranial pressures were reported for only 2 patients; pre- and post-treatment values were not presented. In addition, OFCs were not reported. Increases in these infants' OFCs might be expected if communicating hydrocephalus is associated with distension of the subarachnoid space and enlargement of the ventricles. In our patients, there were no significant changes in the OFC, although changes were observed on CT. Siemes et al. [10] studied the pre- and post-treatment CSF in 20 children with infantile spasms. The CSF protein pattern was abnormal and consistent with increased cerebrovascular permeability for proteins, especially for albumin, but did not document increased gamma globulin, which is present in acute or chronic central nervous system infections. After 2-3 weeks of ACTH therapy, the CSF protein pattern normalized. The authors suggested that the changes in CT and CSF could be explained partially by reduction of cerebral swelling. CT findings and their correlation with the CSF changes were not presented in that report. Their findings are at some variance with the findings and suggestions of Lyen et al. [9[ and Carollo et al. [8], since an evolving, communicating hydrocephalus would be expected to be associated with abnormal blood-brain barrier function and CSF absorption. The persistence of CT changes in 44 % of our patients 4 to 6 weeks after discontinuance of hormonal therapy suggests that these changes were probably not secondary to water shifts or to a communicating hydrocephalus.
The pathophysiology of hormone-induced CT changes in infants with infantile spasms remains unknown. Since these changes occur even with relatively low dosages and short durations of therapy and may persist for weeks after discontinuance of hormonal therapy, further investigation of the clinical and biochemical effects of ACTH and prednisone is warranted. This work was supported by grant NS 11535 from the National Institute of Neurological and Communicative Disorders and Stroke, NIH. References [1] Ham K, Watanabe K, Miyazaki S, et al. Apparent brain atrophy and subdural hematoma following ACTH therapy. Brain Dev 1981;3:45-9. [2] Lagenstein I, Willig RP, Kuhne D. Cranial computerized tomography (CCT) findings in children treated with ACTH and dexamethasone: First results. Neuropaediatrie 1979;10:370-84.
[3] Maekawa K, Ohta H, Tamai I. Transient brain shrinkage in infantile spasms after ACTH treatment. Report of two cases. Neuropediarrics 1980; 11:80-4. [4] Frost JD Jr, Hrachovy RA, Kellaway P, et al. Quantitative analysis and characterization of infantile spasms. Epilepsia 1978;19:273-82. 151 Kellaway P, Hrachovy RA, Frost JD Jr, et ai. Precise characterization and quantification of infantile spasms. Ann Neurol 1979;6:214-8. [6] Gastaut H, Gastaut JL, Regis H, et al. Computerized tomography in the study of West's syndrome. Dev Med Child Neurol 1978;20:21-7. [7] Singer WE), Hailer JS, Sullivan LR, et ai. The value of neuroradiology in infantile spasms. J Pediatr 1982; 100;47-50. [8] Carollo C, Marin G, Scanarini M, et al. CT and ACI'H treatment in infantile spasms. Childs Brain 1982;9:347-53. [9] LyenKR, Holland IM, Lyen YC. Reversible cerebral atrophy in infantile spasms caused by corticotropin. Lancet 1979;2:237-8. [10] Siemes H, Rating D, Hanefeld F. Infantile spasms: CSF proteins before and during treatment with ACTH. Dev Med Child Neurol 1981;23:384.
Glaze et al: Therapy of Infantile Spasms
27