Botulinum Toxin Type A in the Management of Cerebral Palsy: Low or High Dose?

Correspondence Oligohydrosis and Topiramate To the Editor: Cerminara et al. reported a 4½ year old female with hypohydrosis associated with the use of topiramate, who presented with episodic hyperthermia [1]. We were interested in this potentially serious phenomenon, having documented a similar case in September 2005 (unpublished). Our patient was a 9-year-old with frequent complex partial seizures. Topiramate was commenced and stepped up to 7.8 mg/kg/day over 2 weeks in order to control the frequent seizures. Hypohydrosis was evident soon afterward with his mother observing that he became flushed and appeared unable to sweat despite high ambient temperature. The symptoms subsided after cessation of topiramate. There has also been a recent report of residual cerebellar and cognitive dysfunction after topiramate-associated hyperthermia in an adult [2]. While the causative role of topiramate may still be difficult to confirm, we believe that this appears to be an important side effect that needs to be recognized so as to avoid unnecessary investigations, especially when patients present with vague symptoms such as fatigue and hyperthermia. It is also interesting to speculate whether this phenomenon may be more frequent in hotter climates, as the majority of the reported cases have come from Spain, during the hotter summer months [3,4]. Eva L.W. Fung, MBChB Edmund A.S. Nelson, MD Department of Paediatrics The Chinese University of Hong Kong Hong Kong SAR, China References [1] Cerminara C, Seri S, Bombardieri R, Pinci M, Curatolo P. Hypohidrosis during topiramate treatment: A rare and reversible side effect. Pediatr Neurol 2006;34:392-4. [2] Galicia SC, Lewis SL, Metman LV. Severe topiramate-associated hyperthermia resulting in persistent neurological dysfunction. Clin Neuropharmacol 2005;28:94-5. [3] Arcas J, Ferrer T, Roche MC, Martinez-Bermejo A, LopezMartin V. Hypohidrosis related to the administration of topiramate to children. Epilepsia 2001;42:1363-5. [4] Nieto-Barrera M, Nieto-Jimenez M, Candau R, Ruiz del Portal L. Anhidrosis and hyperthermia associated with treatment with topiramate. Revista de Neurologia 2002;34:114-6.

Botulinum Toxin Type A in the Management of Cerebral Palsy: Low or High Dose? To the Editor: We read with interest the recently published study by Cardoso et al. describing the data of published double-blind, randomized clinical trials to assess, with a meta-analysis, if botulinum toxin type A is an adequate treatment for spasticity caused by cerebral palsy [1]. We agree with the authors in that the clinical effects of botulinum toxin type A (BTX-A) have been reported to include decreased spasticity and increased range of motion. It can be one

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of the main tools to improve prognosis in children with cerebral palsy. However, important points need to be clarified. Since its initial use in pediatric patients, as first reported in 1993, BTX-A, a relatively recent addition to the available medical interventions for children with cerebral palsy, has rapidly gained acceptance as a treatment of spasticity. However, no consensus exists among clinicians about how an optimal dose of BTX-A should be determined, and there are no standard guidelines on doses of BTX-A in children [2]. Doses of 2-6 U/kg body weight per muscle with a maximum total dose of 29 U/kg have been reported. A review of previous publications indicates that the dose that has been used for children with cerebral has increased over time [3]. In this study, six double-blind, placebocontrolled studies were reviewed with meta-analysis. However, no information was given about the exact dosages of BTX-A used in these clinical studies. Another point is that without knowing the dosage ranges of BTX-A in these studies, it is hard to conclude that BTX-A has minor side effects with significant gait improvements. In this article, the dosage ranges of BTX-A per kilogram are missing and need to be clarified. Alper I. Dai, MD Department of Pediatrics, Division of Pediatric Neurology School of Medicine, Gaziantep University 27310 Gaziantep, Turkey

References [1] Cardoso ES, Rodrigues BM, Barroso M, et al. Botulinum toxin type A for the treatment of the spastic equinus foot in cerebral palsy. Pediatr Neurol 2006;34:106-9. [2] Nolan KW, Cole LL, Liptak GS. Use of Botulinum toxin type A in children with cerebral palsy. Phys Ther 2006;86:573-84. [3] Flett PJ. Rehabilitation of spasticity and related problems in childhood cerebral palsy. J Paediatr Child Health 2003;39:6-14.

Response: We appreciate the interest and the comments by Dr. Dai regarding our meta-analysis on botulinum toxin in equinus foot. Dr. Dai stresses important points to all physicians who inject botulinum toxin type A (BTX-A), which are the different doses reported in the literature, and the occurrence of side effects after BTX-A injection. In Table 1 we can observe the doses used in the papers of our meta-analysis [1-6]. As we can see, they ranged from 15 to 30 units of Dysport, and 1 to 7.3 units of Botox. The second point is the minor side effects observed by the majority of authors, despite the improvement in gait. We agree that doses of BTX-A have increased since this therapy was first introduced; however, as several authors have pointed out, there is an optimal dose to be injected, and although we do not have information about the therapeutic window of BTX-A, the maximum doses described in the literature are safe, with self-limited side effects [7-10]. So, it is important to find the appropriate dose that improves function, for each patient. Although the majority of papers recommend a usual range, the physician has to discuss with the rehabilitation team and the patient the goals to be

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