Pisciotta Livia, Gherzi Marcella, Stagnaro Michela, Calevo Maria Grazia, Giannotta Melania, Vavassori Maria Rosaria, Veneselli Edvige, De Grandis Elisa
Child Neuropsychiatry Unit, Istituto Giannina Gaslini, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics and Maternal and Children's Sciences, University of Genoa, Genoa, Italy.
Epidemiology, Biostatistics and Committees Unit, Istituto Giannina Gaslini, Genoa, Italy.
Brain Dev. 2017 Jun;39(6):521-528. doi: 10.1016/j.braindev.2017.02.001. Epub 2017 Feb 27.
Alternating Hemiplegia of Childhood (AHC) is a severe disorder. Several drugs have been administered as prophylaxis for paroxysmal attacks, however, no therapy is completely effective.
Our aim is to review the pharmacological data related to the prophylactic and acute treatment of a cohort of 30 patients (16M, 14F, age range 5-42years) and to correlate them with the clinical and genetic data collected through the Italian Biobank and Clinical Registry for AHC.
Flunarizine was the most commonly used long-term treatment in the cohort; it reduced duration and frequency of attacks in 50% of patients and decreased intensity in 32.1%. In younger patients, flunarizine seemed significantly more effective in reducing intensity. We found no correlation between the effectiveness of flunarizine and genotype, or between developmental outcome and duration of treatment. In particular, 3 of our patients affected by E815K mutation presented rapid neurological deterioration despite ongoing treatment. Among the other administered prophylactic therapies, few proved to be effective (benzodiazepines, niaprazine, acetazolamide, melatonin, olanzapine, ketogenic diet). No clear rationale exists regarding their use, but these therapies may work by reducing the triggering factors.
The presented data are retrospective, but they are aimed at filling a gap given the rarity of the disease and the lack of randomized and controlled studies. Besides their usefulness in clarifying the pathophysiology of the disease, prospective studies involving larger cohorts of ATP1A3 mutated AHC patients are needed to provide a rationale for testing other molecules.
儿童交替性偏瘫（AHC）是一种严重疾病。已有多种药物用于预防阵发性发作，但尚无治疗方法完全有效。
我们的目的是回顾30例患者（16例男性，14例女性，年龄范围5 - 42岁）预防和急性治疗的药理学数据，并将其与通过意大利AHC生物样本库和临床登记处收集的临床及基因数据相关联。
氟桂利嗪是该队列中最常用的长期治疗药物；它使50%的患者发作持续时间和频率降低，32.1%的患者发作强度降低。在较年轻患者中，氟桂利嗪在降低发作强度方面似乎明显更有效。我们发现氟桂利嗪的疗效与基因型之间、发育结局与治疗持续时间之间均无相关性。特别是，我们有3例携带E815K突变的患者尽管持续治疗仍出现快速神经功能恶化。在其他使用的预防性治疗中，很少有被证明有效的（苯二氮䓬类、尼阿嗪、乙酰唑胺、褪黑素、奥氮平、生酮饮食）。关于它们的使用尚无明确的理论依据，但这些治疗可能通过减少触发因素起作用。
所呈现的数据是回顾性的，但鉴于该疾病的罕见性以及缺乏随机对照研究，旨在填补空白。除了有助于阐明疾病的病理生理学外，还需要对更大队列的ATP1A3突变AHC患者进行前瞻性研究，为测试其他分子提供理论依据。
