Correspondencd TREATMENT

OF INFANTILE

SPASMS

To the Editor: I read with great interest the review article about the treatment of infantile spasms by O. Carter Snead [I]. I noted that the author did not mention that niwazepam is effective in controlling the spasms. The effectiveness of fllis benzodiazepine in the treatment of infantile spasms had been reported by Volzke et al. [2], Jan et al. [3], and Lyon and Evrard [4]. According to these authors and to my practice I found that it represents, fin'st of all, an alternative treatment when there is a contraindieation to ACTH. Second, it could be administered as a first step in the treatment of any case of West syndrome because the treatment response is all or none. When spasms persist after 3-4 days of treatment with nitrazepam, ACTH must be substituted. Nitrazepam also may be used to avoid relapse during the ACTH reduction period and 6 months after ACTH has been discontinued. In addition, after comparing the undesirable effects of nitrazepam to the dangerous side effects of ACTH and steroids, I believe that nitrazepam therapy is worth considering in this condition.

Najoua Miladi, MD National Institute of Neurology La Rabta, Tunis References [1] Snead OC. Treatment of infantile spasms. Pediatr Neurol 1990; 6:147-50. [2] Volzke E, Doose H, Stephan E. The treatment of infantile spasms and hypsarrhythmia with Mogadon. Epilepsia 1967;8:64-70. [3] J a n JE, Riegl JA, Crichton JU, Dunn HG. Nitrazepam in the treatment of epilepsy in childhood. Can Med Assoc J 1971;104:571-5. [4] Lyon G, Evrard PH. Neurop6diatfie. Paris: Masson, 1987;124-6.

To the Editor: It is certainly true that the efficacy of nitrazepam in the treatment of infantile spasms has been demonstrated in the past [1]. However, this drug is still not available in the United States; therefore, I did not discuss it at length because, from a practical point of view, it cannot be used readily in the United States and our experience is limited.

O. Carter Snead, III, MD Childrens Hospital Los Angeles Los Angeles, California Reference [1] Dreifuss F, Farwell J, Holmes G, et al. Infantile spasms. Comparative trial of nitrazeparn and corticotropin Arch Neurol 1986;43: 1107-10.

MECHANISMS

OF AED ACTION

To the Editor: In the excellent review article about mechanisms of antiepileptic drug (AED) action [1], Talwar discussed mechanisms of AEDs that affect sustained repetitive firing, post-tetanic potentiation, calcium channels, GABA-mediated inhibition, or inhibition of excitatory receptors. The mechanism of action of acetazolamide, an AED of value as adjunct therapy in the treatment of pediatric epilepsy [2], is unique and may deserve inclusion.

72

PEDIATRIC NEUROLOGY

Vol. 7 No. 1

~LtEWfolamide, a sulfonamide with a free-SO2NH2 group, is an inhibitor of the enzyme carbonic anhydrase. The AED effect is independent of the action on the kidney and the resultant metabolic acidosis, and is correlated directly with the inhibition of carbonic anhydrase in the brain [3]. The maximum degree of enzyme inhibition corresponds with the time of peak AED effect and parallels the concentration of the inhibitor in the brain. The inhibition of carbonic anhydrase located in glial cells causes carbon dioxide accumulation and changes in acid-base and electrolyte balance, with consequent reduction in neuronal excitability. Studies of the development of seizure patterns in newborn animals and their control with acetazolamide show a close correlation with the maturation of brain carbonic anhydrase [4]. Brain carbonic anhydrase is essential for the propagation and generalized spread of a seizure discharge. Low levels of enzyme activity may be sufficient for a focal discharge and the induction of a partial seizure, while a relatively high degree of activity may be required for the propagation of a generalized tonic seizure. The tonic seizure pattern exhibited by older rats is abolished by small doses of acetazolamide, whereas the clonic pattern predominating in 15- to 20-day-old rats is controlled only by large doses [4]. In children with generalized tonic-clonic and myoclonic seizures, the tonic seizure is controlled more effectively than the myoclonic pattern [2]. The development of tolerance to the AED effect of acetazolamide limits its clinical efficacy in children [2]. If potent congeners of acetazolamide are developed that can reach higher concentrations in the brain, they should exhibit greater AED activity and clinical usefulness. Further studies of the mechanism of tolerance and its prevention would enhance AED efficacy in long-term therapy in children. J. Gordon Millichap, MD Southern Illinois University School of Medicine Springfield. Illinois References [1] Talwar D. Mechanisms of antiepileptic drug action. Pediatr Neurol 1990;6:289-95. [2] Millichap JG. Anticonvulsant action of acetazolamide (Diamox) in children. Neurology 1956;6:552-9. [3] Millichap JG, Woodbury DM, Goodman LS. Mechanism of the anticonvulsant action of acetazolamide, a carbonic anhydrase inhibitor. J Pharmacol Exp Ther 1955; 115:251-8. [4] Milllchap JG. Development of seizure patterns in newborn animals. Significance of carbonic anhydrase, parts I and II. Proc Soc Exp Biol Med 1957;96:125-9, 1958;97:606-11.

To the Editor: Dr. Millichap has outlined well the possible mechanisms of action of acetazolamide, an adjunctive AED. Efficacy of low-to-medium dose acetazolamide, as adjunctive therapy, in the treatment of refractory partial seizures (without significant problems with tolerance) has recently been reported [1]. The author thanks Dr. Millichap for highlighting known mechanisms of action of this intriguing AED, and emphasizing the role this understanding may play in the future development of AEDs.

Dinesh Talwar, MD University of Minnesota Hospital and Clinics Minneapolis, Minnesota Reference [1] Oles KS, Penry JK, Cole DLW, Howard G. Use of acetazolamide as an adjunct to carbamazepine in refractory partial seizures. Epilepsia 1989;30:74-8.

Treatment of infantile spasms.

Correspondencd TREATMENT OF INFANTILE SPASMS To the Editor: I read with great interest the review article about the treatment of infantile spasms b...
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