儿童交替性偏瘫六例分析

目的探讨儿童交替性偏瘫（ＡＨＣ）的临床特点及治疗方法。方法对６例ＡＨＣ患儿的临床资料进行分析。结果６例患儿的临床特征为出生后１８个月起内病，频繁发作，持续数分钟至数小时；短暂的眼球震颤，肌张力异常，舞蹈徐动样动作，植物神经机能紊乱和认知机能减退；睡眠可缓解无力及锥体外系症状。应用氟桂嗪治疗后，１例患儿发作完全停止，其余５例患儿均显示发作频率和持续时间降低。结论本病的主要特征为１８个月内起病的发作性交替性偏瘫，伴锥体外系症状及智力障碍，氟桂嗪治疗本病有效     

三例儿童交替性偏瘫的回顾性分析

目的探讨儿童交替性偏瘫病因、临床特点、治疗效果。方法回顾性分析3例儿童交替性偏瘫患者的病因、临床表现及疗效。结果本组3例患者起病年龄均小于18个月,反复发作的交替性偏瘫；进行性的智能障碍,其中1例伴有短暂眼球震颤及眼球活动障碍,1例伴有张力障碍性姿势异常；睡眠可缓解无力及锥体外系症状,应用氟桂嗪治疗后,2例患者发作频率及持续时间降低,1例无效。结论本病病因不明,多为散发,临床表现为18月内起病的发作性交替性偏瘫,辅助检查无特征性改变,氟桂利嗪治疗部分有效。     

Alternating hemiplegia of childhood: New diagnostic options

A syndrome of alternating hemiplegia of childhood (AHC) is a rare disorder first presented in 1971. AHC is characterized by transient episodes of hemiplegia affecting either one or both sides of the body. Age of onset is before 18 months and the common earliest manifestations are dystonic or tonic attacks and nystagmus. Hemiplegic episodes last minutes to days and the frequency and duration tend to decrease with time. Motor and intellectual development is affected, deficits may also develop later. Epileptic seizures occur in some patients. Neuroimaging of the brain usually reveals no abnormalities. The variability of individual clinical presentations and evolution of symptoms have made diagnosis difficult. Therefore the problems of misdiagnosis could account for the low prevalence of this syndrome. This paper hopes to present actual data on AHC, especially of the results of genetic research and new diagnostic tools.     

Alternating hemiplegia of childhood: no mutations in the glutamate transporter EAAT1

Alternating hemiplegia of childhood (AHC) is a severe brain disorder, mainly characterised by episodes of hemiplegia, progressive mental retardation, and other severe paroxysmal and permanent neurological symptoms. Clinically and genetically, there is some overlap with sporadic (SHM) and familial (FHM) hemiplegic migraine, a severe monogenic subtype of migraine. Although no mutations were detected in the FHM1 CACNA1A and FHM2 ATP1A2 genes in sporadic AHC patients, a mutation was found in the FHM2 ATP1A2 gene in a family with AHC. Recently, a missense mutation was found in the SLC1A3 gene that encodes the glutamate transporter EAAT1, in a patient with alternating hemiplegia, episodic ataxia, seizures, and headache. Because of the remarkable clinical similarities and the potential role of glutamate in AHC, we analysed six sporadic patients with AHC for mutations in the SLC1A3 gene. No mutations were found. The SLC1A3 EAAT1 glutamate transporter gene does not seem to be involved in the pathogenesis of AHC.     

Topiramate: a new agent for patients with alternating hemiplegia of childhood

Alternating hemiplegia of childhood is a rare syndrome characterized by the onset, before 18 months of age, of frequent attacks of alternating paralysis. Here we report the efficacy of topiramate in four patients with alternating hemiplegia of childhood (AHC) that did not respond to flunarizine, as well as in two newly diagnosed patients. Following treatment with topiramate, the frequency and duration of hemiplegic attacks significantly improved in all patients. Additional symptoms such as seizures, migraine, involuntary movements, autonomic symptoms, and impaired mental development also improved. Topiramate is worth trying when treating patients with AHC as a first trial, or a substitute for flunarizine once the latter agent loses effect.     

Absence of mutation in the SLC2A1 gene in a cohort of patients with alternating hemiplegia of childhood (AHC)

Alternating hemiplegia of childhood (AHC) is a rare neuropediatric disorder classically characterized by episodes of hemiplegia developing in the first months of life, various non-epileptic paroxysmal events and global neurological impairment. If the etiology is unresolved, the disorder is highly suspected to be monogenic with DE NOVO autosomal dominant mutations. A missense mutation in the SLC2A1 gene encoding the facilitative glucose transporter-1 (GLUT1) was recently described in a child fulfilling the existing criteria for the diagnosis of AHC, with the exception of age at onset, thus suggesting a clinical overlap between AHC and GLUT1 deficiency syndrome due to SLC2A1 mutations. We have studied a cohort of 23 patients to investigate whether patients with classical AHC harbor SLC2A1 mutations. Automated Sanger sequencing and MLPA analyses failed to detect any SLC2A1 mutations in the 23 patients analyzed, thus excluding mutations of this gene as a frequent cause of classical AHC.     

Absence of small-vessel abnormalities in alternating hemiplegia of childhood

Objective: To investigate whether Japanese patients with alternating hemiplegia of childhood (AHC) have the similar small-vessel abnormalities in skin reported in European patients with AHC. Methods: Electron microscopic observation of biopsied skin specimens were carried out in six Japanese patients with AHC. All patients (aged 5-17, all boys) had been diagnosed with AHC through their typical clinical courses and symptoms. Results: No abnormal findings in both endothelial cells and smooth muscle cells in skin small-vessels were obtained in the present study, either in the five flunarizine responders or in the one non-responder. Conclusions: From our observations, we hypothesized that there may be some subtypes of AHC. The diverse clinical courses in patients with AHC and the differing efficacy of flunarizine treatment could be explained because of the heterogeneity of AHC subtypes.     

An 11-year follow-up study of neonatal-onset, bath-induced alternating hemiplegia of childhood in twins

The authors previously reported on the initial manifestations in a set of female twins, who presented soon after birth with bath-induced paroxysmal events each time they were immersed in a warm water bath. These episodes progressively ceased by the age of 36 months, replaced by paroxysmal episodes of alternating hemiplegia unrelated to water immersion. By age 4 years, the twins developed the classic features of alternating hemiplegia of childhood. Clinical outcomes at the age of 11 years are now reported. Standard and video-electroencephalograms showed a large, slow background activity followed by lower amplitude waves without focal abnormalities or other abnormal findings. This represents the first report on (a) alternating hemiplegia of childhood started with bath-induced paroxysmal episodes; (b) this condition in monozygotic twins; and (c) an 11-year follow-up study in which the twins continue to experience episodes of alternating hemiplegia in the setting of baseline cognitive impairment without epileptic episodes.     

Benign nocturnal alternating hemiplegia of childhood: The first clinical report with paroxysmal events home‐video recordings

Benign familial nocturnal alternating hemiplegia of childhood (BNAHC) is a rare disorder characterized by recurrent attacks of hemiplegia, arising from sleep without progression to neurological or intellectual impairment. It is distinct from the malignant, relatively more common, alternating hemiplegia of childhood (AHC), complicated by developmental deterioration, cognitive impairment, and permanent neurological deficits such as choreoathetosis. The authors add a new case of BNAHC to the pertinent literature and report, for the first time, a video with the typical nocturnal hemiplegic attacks in order to improve knowledge about this disorder among child neurologists and pediatricians and increase the possibility of clarifying its pathogenesis and molecular basis. © 2008 Movement Disorder Society     

Successful trial of amantadine hydrochloride for two patients with alternating hemiplegia of childhood

We report here the efficacy of amantadine hydrochloride for two patients with alternating hemiplegia of childhood (AHC) that did not respond to flunarizine. Amantadine was administered to one patient at age one year and seven months and to the other at age 25 years. The frequencies and duration of the hemiplegic attacks significantly improved in both patients. However, the attacks gradually returned to the previous level after a significant reduction in seizures for three years in the younger patient with ongoing AHC. Our therapeutic results further support the hypothesis that glutamate and NMDA receptors are involved in inducing alternating hemiplegic attacks, because amantadine as well as its derivative, memantine, are clinically available non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, with neuroprotective effects. Amantadine is worth trying when treating patients with AHC as a first trial or a substitute for flunarizine once the latter agent looses effect.     

Long-term effect of flunarizine on patients with alternating hemiplegia of childhood in Japan

To determine the effect of flunarizine therapy on patients with alternating hemiplegia of childhood (AHC), we sent a questionnaire by mail to council members of the Japanese Society of Child Neurology. We collected 28 AHC patients, and studied their clinical courses and the effects of drug therapy. All of the patients had received flunarizine. In 18 of the 28 patients, flunarizine reduced the severity, duration, or frequency of the hemiplegic attacks. No other drug was more effective than flunarizine. Some flunarizine non-effective patients were severely deteriorated, for example, they had dementia or were ventilator-assisted. Flunarizine had not only a short-term effect, i.e. it reduced the hemiplegic attacks, but also a long-term effect on the motor and intellectual development in some patients with AHC. Flunarizine is still an essential drug for treating AHC.     

Alternating Hemiplegia of Childhood With a de Novo Mutation in ATP1A3 and Changes in SLC2A1 Responsive to a Ketogenic Diet

BackgroundAlternating hemiplegia of childhood (AHC) is a rare condition characterized by an early onset of hemiplegic episodes and other paroxysmal or permanent neurological dysfunctions. Recently, mutations in the ATP1A3 gene have been identified as the causal mechanism of AHC. Regarding the differential diagnosis of AHC, glucose transporter 1 deficiency syndrome may be considered because these two disorders share some paroxystic and nonparoxystic features.Patient and resultsWe report a typical case of AHC harboring a de novo mutation in the ATP1A3 gene, together with a duplication and insertion in the SLC2A1 gene who exhibited marked clinical improvement following ketogenic diet.ConclusionBecause the contribution of the SLC2A1 mutation to the clinical phenotype cannot be definitely demonstrated, the remarkable clinical response after ketogenic diet led us to the hypothesis that ketogenic diet might be effective in AHC as it provides an alternative energy source for the brain.     

A boy with nystagmus, refractory dystonia and apneic attack due to alternating hemiplegia of childhood

We herein report the findings of a 2-year-6-month-old boy, who had been experiencing monocular pendular nystagmus, strabismus, and episodic eye deviation nystagmus, intractable dystonia and apneic attack which all began when he was 2 days of age. He underwent a complete blood count test, blood chemistry test, analysis of amino acids in the blood and urine, analysis of pyruvate/lactate in blood and cerebrospinal fluid, head computed tomography and magnetic resonance imaging and no abnormal results were identified. His attacks were resistant to multiple antiepileptic and dopaminergic drugs. He showed transient left and/or right hemiplegia after nystagmus, dystonia and/or apneic attacks at 8-months of age with retardation in intelligence. We diagnosed him to have alternating hemiplegia of childhood (AHC). We were unsure how to deal with his attacks after he was discharged from the hospital, however, resuscitation with the ambu bag by his mother at home and the intravenous infusion of diazepam or thiamylal at the hospital together was proven to be an effective method for treating his severe apneic attacks. The effect of diazepam and amantadine on these attacks was transient, however, the administration of flunarizine with amantadine resulted in an improvement in his attacks. We therefore consider the administration of flunarizine to be essential for the effective treatment of AHC in this case.     

Benign nocturnal alternating hemiplegia of childhood: six patients and long-term follow-up.

Benign familial nocturnal alternating hemiplegia of childhood refers to recurrent attacks of hemiplegia arising from sleep, described in young children without neurologic or mental impairment. It is probably migraine related. The authors report two unrelated patients with nocturnal attacks starting at 22 and 31 months, followed by daytime episodes in one. The authors confirm the benign course of this disorder. It is distinct from the classic malignant form of alternating hemiplegia of childhood.     

儿童交替性偏瘫一例

目的了解儿童交替性偏瘫(AHC)的诊断及治疗方法的合理选择。方法介绍我院收治的1例难治的儿童交替性偏瘫患儿的临床特点,检索国内外10年内的相关文献。结果本病的临床特点为反复发作性的偏瘫,睡眠后缓解,可有其他发作性症状,如发作性肌张力障碍、眼球运动异常和认知障碍等。氟桂利嗪是最常用的药物,托吡酯片、阿立哌唑也可用于治疗本病。结论本病是一种罕见的神经系统发作性疾病,临床表现多样,容易误诊,目前没有标准的治疗方法。     

Ictal 99mTc-HMPAO SPECT in alternating hemiplegia

99mTc-hexamethylpropylenamine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) was performed in a patient with alternating hemiplegia during 2 episodes of the disease. The regional cerebral blood flow patterns correlated with the clinical manifestations during both episodes. Hyperperfusion of the contralateral hemisphere was suggested by asymmetric 99mTc-HMPAO uptake, whereas symmetric 123I-N-isopropyl-p-iodoamphetamine uptake was detected during the interictal period. The results suggested that alternating hemiplegia in infants represents an atypical manifestation of epilepsy, despite the lack of paroxysmal electroencephalographic abnormalities during the episodes. 99mTc-HMPAO SPECT appears to be a useful method for detecting transient regional cerebral blood flow alterations during paroxysmal events because the tracer is rapidly available for emergencies and retains a fixed distribution for 5-8 hours, sufficient time to allow for SPECT acquisition.     

Neonatal onset of hot water reflex seizures in monozygotic twins subsequently manifesting episodes of alternating hemiplegia

We report on monozygotic twins with neonatal onset of daily reflex seizures triggered by hot water. Video record during the hot water bathing showed clinical signs consistent with a reflex seizure. The numbers of episodes were markedly reduced when the mother began bathing the children with reduced temperature bath water. At the age of 20 months, the twins developed episodes of paroxysmal disturbances including alternating hemiplegia. These two patients are the youngest reported cases of reflex hot water seizures, and the only reported cases in which reflex hot water seizures subsequently manifested episodes of alternating hemiplegia.     

Alternating hemiplegia of childhood and a pathogenic variant of ATP1A3: a case report and pathophysiological considerations

We describe a case of a child suffering from alternating hemiplegia with a heterozygous p. E815K pathogenic variant of ATP1A3. The patient started to present abnormal eye movements in the first days of life, followed by the appearance at 2 months of dystonic episodes, and later on, by recurrent episodes of alternating hemiplegia more often on the right side. A severe epilepsy started at the age of 2 years with episodes of status epilepticus since the onset which frequently recurred, requiring admission to the intensive care unit. MRI showed bilateral mesial temporal sclerosis and a left‐sided ischaemic lesion. Interictal EEG showed bilateral abnormalities, whereas postictal EEG after status epilepticus showed overt slowing on the left side, suggesting a predominant involvement of ictal activity of the left hemisphere. We hypothesize that in our patient, the left hemisphere might have been more prominently affected by the pathogenetic abnormalities underlying alternating hemiplegia of childhood, rendering it more prone to early ischaemic lesions and recurrent unilateral status epilepticus. We speculate whether alternating hemiplegia of childhood shares some common pathophysiological mechanisms with familial hemiplegic migraine that may be associated with a pathogenic variant of ATP1A2.     

A patient with alternating hemiplegia in childhood

Alternating hemiplegia in childhood (Verret, 1971) is a disorder presenting with frequent episodes of alternating hemiplegia from early infancy. We report a patient with this disorder, along with a pathophysiological study and a discussion about the available therapies for this disorder. The patient, an 11-year-old boy, visited our hospital with episodes of alternating hemiplegia from early infancy. His family history showed that many members suffered from migraine. He was born with asphyxia. Mental and motor developmental delays were seen from early infancy. The hemiplegic episodes with ipsilateral facial palsy had occurred frequently from early infancy. The episodes were frequently induced by emotional stress. The duration of hemiplegia varied from 10 minutes to 3 days. From the age of 11 years, he had begun to have migrainous attacks with or without hemiplegic episodes. Neurological examination revealed slight muscle hypotonia, choreoathetosis and dystonic movements induced by locomotion, positive Myerson sign, increased deep tendon reflexes and Babinski reflex. CAG, VAG and CAT revealed normal findings. EEG revealed diffuse generalized slowing during hemiplegic episodes. Measurement of regional cerebral blood flow (CBF) by 133Xe inhalation method revealed a slight decrease of bilateral CBF during a quadriplegic episode. Positron emission tomography using C15O2 revealed a slight decrease of CBF at the insula, putamen and claustrum of the left side during a right sided episode. Increased excretion of urinary 5-HIAA was seen during one episode. From our clinical and laboratory findings, we think this disorder may be a special type of migraine. Therapeutic trials of diazepam and flunarizine were both effective, but the initial effectiveness was decreased after 5 months.     

Alternating hemiplegia of childhood: no mutations in the second familial hemiplegic migraine gene ATP1A2

Alternating hemiplegia of childhood (AHC) is a rare disorder mainly characterised by attacks of hemiplegia and mental retardation. AHC has often been associated with migraine. Previously, we have excluded the involvement of the familial hemiplegic migraine (FHM) CACNA1A gene in four patients with AHC. A second gene for FHM was discovered recently: the ATP1A2 gene on chromosome 1q23, coding for the alpha 2 subunit of Na+,K+-ATPase. We performed a mutation analysis of the ATP1A2 gene in six patients, using direct sequencing, but found no mutations in any of the 23 exons. Other cerebral ion channel genes remain candidate genes for AHC.