flunarizine and Hemiplegia

Alternating hemiplegia of childhood is a severe neurological disorder with infantile-onset recurrent episodes of hemiplegia on either side of the body and other paroxysmal events such as seizures, dystonia, tonic episodes, abnormal eye movements or autonomic dysfunction, primarily due to de novo pathogenic mutations in the ATP1A3 gene. The burden of neuromorbidities is significant and includes epilepsy; attention-deficit/hyperactivity disorder; behavioral difficulties; motor, cognitive, adaptive, and learning impairment; ataxia; movement disorders; and migraine. Comprehensive multispecialty clinic with the availability of various specialists with considerable experience in alternating hemiplegia of childhood is beneficial. A comprehensive treatment plan including strict maintenance of a diary about different paroxysmal events is helpful. Disease-modifying therapy of alternating hemiplegia of childhood does not exist, and several agents such as benzodiazepines, flunarizine, topiramate, ketogenic diet, triheptanoin, steroid, amantadine, memantine, aripiprazole, oral ATP, coenzyme Q, acetazolamide, dextromethorphan, and vagus nerve stimulator have been tried with various rates of success by aborting attacks or reducing the frequency or severity of paroxysmal spells. The apparent efficacy of flunarizine is based on its use in hundreds of patients, albeit in open-label experience, but most of the other agents' reports of efficacy were from single case reports or case series of only a handful of patients. Besides reviewing existing data about individual agent active against paroxysmal events, we also review the management principles for coexisting neurological issues. However, with rapid advancement in the understanding of molecular pathogenesis and network abnormality of this disease, the treatment paradigm of alternating hemiplegia of childhood may significantly alter over the next decade.

Topics: Anticonvulsants; Calcium Channel Blockers; Diet, Ketogenic; Flunarizine; Hemiplegia; Humans; Topiramate

In 1890 four cases of headache associated with visual symptoms and hysterical disorder were described by the French neurologist Babinski as migraine ophthalmique hystérique, or hysterical ophthalmic migraine. Since that time this association has seldom been described, and the possibly high frequency previously reported still remains to be established. This paper has reused Babinski's description and it tries to rehabilitate the syndrome described by the French semiologist across the relatively frequent experience of this type of patients in a public hospital. Also it analyzes the reason of the oblivion of his description.. This study presents a series of 43 cases of headache of the migraine type associated with other symptoms, most consistent with basilar-type migraine according to IHS criteria. Diagnosis of conversion disorder (hysteria) was grounded in the criteria set forth in the DSM-IV.. All patients exhibited one or more manifestations of hysteria (conversion symptoms) during migraine attacks, and some did in the intervals between attacks as well. Details of the headaches, associated symptoms, and hysterical manifestations are discussed. Most patients improved with antimigraine medication. Altered consciousness may have contributed to the onset of hysterical symptoms.. The basilar type migraine associated with conversion symptoms described of systematized form by Babinski, it is not a rare entity. Similar pictures have been described along the history of the medicine. The later silence possibly is due to the historical difficulty in defining accurately the conversión disorders. The Babinskís migraine is a certain well entity and must be recovered for the clinic.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Anti-Anxiety Agents; Anticonvulsants; Antidepressive Agents; Conversion Disorder; Diagnostic and Statistical Manual of Mental Disorders; Electroencephalography; Family; Female; Flunarizine; Hemiplegia; Humans; Hysteria; Male; Mental Disorders; Middle Aged; Migraine Disorders; Pain Measurement; Positron-Emission Tomography; Propranolol; Retrospective Studies; Tomography, X-Ray Computed; Young Adult

Alternating hemiplegia in childhood (AHC) has clinically characteristic features which are easily defined and recognizable. Laboratory investigations were basically normal although they were extensively examined during and between attacks. There is still much debate about its etiology, particularly its relation to migraine or epilepsy. Clinical characteristics of identified 23 AHC in Japanese were presented, which were obtained from a large Japanese cooperative study in 1988. AHC may prove not to be as rare as has been thought.

Topics: Child; Diazepam; Female; Flunarizine; Hemiplegia; Humans; Japan; Models, Biological

Topics: Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Epilepsy; Female; Flunarizine; Hemiplegia; Humans; Male; Migraine Disorders

Twelve children with alternating hemiplegia were treated with the calcium-entry blocker flunarizine for 4 months. All but one patient responded favourably with a reduction in frequency and/or duration and severity of attacks. Interictal symptoms decreased and mental development improved in several patients. Nine of the patients entered a subsequent double-blind placebo-controlled withdrawal study lasting another 4 months. Relapses were observed in part of the placebo as well as of the flunarizine-treated patients. The reason for this is not clear, since it is unlikely that the favourable response during the initial open-label study would be due to a placebo effect, or that tolerance to the drug had developed. Feed-back from the parents rather suggests that stress and tension, which were known trigger factors in a majority of these patients, played a role when the patient was switched to the double-blind treatment. Although the present study is not fully conclusive, apparently because of the use of an inadequate trial design, flunarizine, the first truly promising drug in this disease, deserves further study. An appeal is made to join another international double-blind study.

Topics: Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Europe; Female; Flunarizine; Hemiplegia; Humans; Male; Random Allocation; Recurrence; Stress, Physiological

Topics: Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Epilepsy; Female; Flunarizine; Hemiplegia; Humans; Male; Migraine Disorders

Mutations in the ATP1A3 gene have been associated with several syndromes, including rapid-onset dystonia-parkinsonism, alternating hemiplegia of childhood, and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss. In this clinical commentary, we report a 2-year-old female patient with de novo pathogenic variant in the ATP1A3 gene associated with an early-onset form of epilepsy with eyelid myoclonia. The patient had frequent eyelid myoclonia occurring 20-30 times per day, without loss of awareness or other motor manifestations. EEG showed generalized polyspikes and spike-and-wave complexes maximal in the bifrontal regions, with prominent eye closure sensitivity. A sequencing-based epilepsy gene panel revealed a de novo pathogenic heterozygous variant in ATP1A3. The patient showed some response to flunarizine and clonazepam. This case highlights the importance of considering ATP1A3 mutations in the differential diagnosis of early-onset epilepsy with eyelid myoclonia and the potential benefit of flunarizine in improving language and coordination development in patients with ATP1A3-related disorders.

Topics: Child, Preschool; Dystonic Disorders; Epilepsy; Eyelids; Female; Flunarizine; Hemiplegia; Humans; Mutation; Sodium-Potassium-Exchanging ATPase

Topics: Calcium Channel Blockers; Child, Preschool; Diagnosis, Differential; Female; Flunarizine; Hemiplegia; Humans; Mutation; Sodium-Potassium-Exchanging ATPase; Treatment Failure

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.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Cognition Disorders; Cohort Studies; Female; Flunarizine; Hemiplegia; Humans; Italy; Male; Mutation; Sodium-Potassium-Exchanging ATPase; Young Adult

Alternating hemiplegic of childhood is a predominantly sporadic neurodevelopmental syndrome of uncertain etiology, characterized by alternating transient attacks of hemiplegia. Additional features include tonic fits, dystonic posturing, ocular motor abnormalities and deficits in cognitive functioning.. A girl of 7 years-old with alternating hemiplegic of childhood. The first symptoms debut at 17 months of age in the form of lower limb weakness, migraine, nystagmus and hemiplegic crisis alternating both hemibodies. We administrate the Wechsler Intelligence Scale for Children IV (WISC-IV), the Conners Continuous Performance Test II (CPT-II), the Conners scales for parents (CPRS-48) and teachers (CTRS-28) and the Behavior Rating Inventory Executive Function (BRIEF).. In our study we found deficits in sustained attention, reduced speed of information processing, and difficulties in understanding, speaking and working memory. In addition, parents and teachers reported behavioral disturbances, difficulties inhibition capability, in self-control and in regulating emotions.. Deficits neuropsicologicos en la hemiplejia alternante infantil: estudio de un caso.. Introduccion. La hemiplejia alternante infantil es un sindrome del neurodesarrollo de etiologia incierta, caracterizado por la presencia de ataques transitorios de hemiplejia. Las caracteristicas adicionales incluyen crisis epilepticas, distonia, anomalias motoras oculares y deficits en el funcionamiento cognitivo. Caso clinico. Niña de 7 años con hemiplejia alternante infantil. Los primeros sintomas comenzaron a los 17 meses en forma de debilidad en los miembros inferiores, migrañas, nistagmo y crisis hemiplejicas que alternaban ambos hemicuerpos. Se administro la escala de inteligencia de Wechsler para niños IV (WISC-IV) y el Conners Continuous Performance Test II (CPT-II), asi como las escalas de Conners para padres (CPRS-48) y profesores (CTRS-28) y el Behavior Rating Inventory Executive Function (BRIEF). Conclusiones. En nuestro estudio encontramos deficits en atencion sostenida, reduccion de la velocidad de procesamiento de la informacion, y dificultades en la comprension, expresion verbal y memoria de trabajo. Ademas, los padres y profesores comunicaron conductas problematicas, y dificultades en la capacidad de inhibicion, en el autocontrol y en la regulacion de emociones.

Topics: Attention; Child; Child Behavior Disorders; Comprehension; Emotions; Female; Flunarizine; Hemiplegia; Humans; Memory Disorders; Memory, Short-Term; Mental Processes; Neuroimaging; Neurologic Examination; Neuropsychological Tests; Psychomotor Performance; Severity of Illness Index; Speech Disorders

Alternating hemiplegia of childhood (AHC) is a rare disease characterised by repeated episodes of hemiplegia that alternately affect one side of the body. Onset is usually before the age of 18 months, the episodes last anywhere from a few minutes to several days. In some cases these episodes may even render the early infant quadriplegic for some time if one begins before the previous one has finished or if they occur at the same time. The clinical description includes, in addition to these paralysing attacks, other paroxysmal manifestations that are present in practically all the children diagnosed with this condition and which, moreover, appear earlier. Such manifestations consist in tonic attacks, dystonic attacks, abnormal eye movements and autonomic disorders. The fact that these symptoms precede the typical clinical signs and symptoms often leads to delays in the final diagnosis.. We report the case of a male, aged one year and nine months, who initially presented a clinical picture of tonic seizures at the age of two weeks, which then went on to episodes of hemiplegia that appeared alternately at the age of 11 months. The patient also presented retarded overall psychomotor development. In the early stages of the symptoms he was diagnosed with epilepsy, failed to respond to multiple antiepileptic drugs, and the electroencephalogram, neuroimaging and complementary blood and urine tests were all normal/negative. The patient responded well to flunarizine.. This is the first patient with AHC reported in El Salvador. The early and accurate diagnosis of AHC is essential to be able to establish drug therapy and improve the prognosis and the quality of life of patients and their families.. Hemiplejia alternante de la infancia. Primer caso clinico descrito en El Salvador.. Introduccion. La hemiplejia alternante de la infancia (HAI) es una enfermedad rara, caracterizada por episodios repetidos de hemiplejia que afectan alternativamente a un hemicuerpo, son de inicio preferente antes de los 18 meses, duran de minutos a varios dias, e incluso pueden dejar tetraplejico durante un tiempo al lactante, si antes de que se acabe un episodio comienza otro o si estos ocurren de manera simultanea. La descripcion clinica incluye, ademas de estos ataques plejicos, otras manifestaciones paroxisticas presentes practicamente en todos los niños diagnosticados de este trastorno y que son, ademas, de aparicion mas precoz. Consisten en ataques tonicos, ataques distonicos, movimientos oculares anormales y trastornos autonomicos. El hecho de que estos sintomas precedan a la clinica tipica provoca en bastantes ocasiones un retraso en el diagnostico definitivo. Caso clinico. Varon de un año y nueve meses que inicia clinica de crisis tonicas a las dos semanas de vida, posteriormente episodios de hemiplejia que se manifiestan de forma alternante a los 11 meses de vida, y ademas presenta retraso psicomotor global. Al principio de los sintomas se diagnostico epilepsia, no respondio a multiples farmacos antiepilepticos, y el electroencefalograma, la neuroimagen y las pruebas complementarias en sangre y orina fueron normales/negativos. Presento respuesta favorable a la flunaricina. Conclusion. Es el primer paciente descrito de HAI en El Salvador. El diagnostico precoz y acertado de HAI es fundamental para iniciar farmacoterapia y mejorar el pronostico y calidad de vida de los pacientes y sus familias.

Topics: Anticonvulsants; Brain; Delayed Diagnosis; Developmental Disabilities; Diagnosis, Differential; Diagnostic Errors; El Salvador; Electroencephalography; Epilepsy; Flunarizine; Hemiplegia; Humans; Infant; Intellectual Disability; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Male

Alternating hemiplegia of childhood (AHC) is a rare and intractable disorder. The etiology and standard therapy of AHC remain unknown. The long-term effects of flunarizine or topiramate on patients with AHC are still not clear.. Fifteen patients were investigated in this study. Their neurological disturbance and mental retardation after drug therapy were evaluated.. Nine patients treated with flunarizine therapy and three children with topimarate treatment presented with shorter duration or less frequency of the hemiplegic attacks. These drug responsive patients also showed improvements on neurological disturbance including eye movement disorder, choreoathetotic movements, dystonia, and ataxia. However, seizure episodes and cognitive impairments were not alleviated in AHC with long-term drug therapy.. The findings from the present study support flunarizine or topitamate as the rational treatment for AHC.

Topics: Adolescent; Anticonvulsants; Asian People; Child; Child, Preschool; Female; Flunarizine; Fructose; Hemiplegia; Humans; Intelligence; Longitudinal Studies; Male; Movement Disorders; Nervous System Diseases; Retrospective Studies; Surveys and Questionnaires; Topiramate

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.. 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.. 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.. 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.

Topics: Adolescent; Asian People; Biopsy; Blood Vessels; Calcium Channel Blockers; Child; Child, Preschool; Flunarizine; Hemiplegia; Humans; Male; Skin

Hemiplegic migraine is a rare form of migraine characterized by periodic attacks of migraine with neurologic aura and transient hemiplegia. There are familial and sporadic cases, both on a genetic basis; we describe the case of a 6-year-old boy affected by sporadic hemiplegic migraine, showing a novel ATP1A2 gene missense mutation (p.Gly715Arg) in exon 16. Long-term treatment with flunarizine resulted in good clinical response and prevention of further attacks.

Topics: Anticonvulsants; Child; Flunarizine; Hemiplegia; Humans; Migraine with Aura; Mutation, Missense; Sodium-Potassium-Exchanging ATPase; Treatment Outcome

To define clinical features of patients with alternating hemiplegia of childhood.. We retrospectively reviewed the clinical presentation and course of the disease in patients diagnosed between January 2003 and December 2008 at the Pediatric Neurology Department of the Istanbul Medical Faculty.. The nine patients had a mean age of 6.6 months (2-15 months) at the onset of symptoms. Paroxysmal eye movements were the early symptom of five patients. All patients had recurrent alternating hemiplegic episodes and relief of symptoms while sleeping. Duration of events varied widely from few minutes to several days and was associated with slowly progressive neurological deterioration. Flunarizine might decrease frequency of events but is not effective to neurological deterioration. Amantadine as an alternative agent is used in add-on therapy, but epileptogenic side effect prevented the evaluation of long-term efficacy.. Trials on new agents like amantadine are necessary for more effective control of the disease.

Topics: Amantadine; Anticonvulsants; Antiparkinson Agents; Female; Flunarizine; Hemiplegia; Humans; Infant; Male; Medical Audit; Retrospective Studies; Treatment Outcome; Turkey

Alternating hemiplegia of childhood (AHC) is a rare neurological disorder which usually presents before 18 months of age and is characterised by recurrent alternating episodes of hemiparesis. A single effective treatment for this condition is yet to be established; flunarizine is currently the most widely used but with varying degrees of success. An 18-month-old child presented with AHC and treatment with a combination of topiramate and flunarizine made a significant difference in controlling the frequency and severity of the attacks. This possibly allowed a better developmental outcome than in most children with this condition. Topiramate combined with flunarizine for treating AHC has much potential for further research.

Topics: Anticonvulsants; Flunarizine; Fructose; Hemiplegia; Humans; Infant; Male; Topiramate; Treatment Outcome

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.

Topics: Amantadine; Anticonvulsants; Apnea; Child, Preschool; Dystonia; Flunarizine; Hemiplegia; Humans; Male; Nystagmus, Pathologic; Respiration, Artificial

Alternating hemiplegia of childhood is a rare disorder characterized by recurrent attacks of hemiplegia affecting either side of the body, oculomotor and autonomic disturbances, movement disorders, and progressive cognitive impairment. We report on one family with autosomal dominant alternating hemiplegia. The disorder was first recognized in a 9-year-old child, the third son of the family, who presented with learning disability, tonic-clonic seizures, dystonic attacks, and episodes of alternating hemiplegia starting at the age of 2 1/2 years. His mother and three brothers had similar symptoms. The maternal uncle, who has learning disability, had experienced multiple dystonic attacks. Tests performed on the family, including computerized tomography, magnetic resonance imaging, and magnetic resonance angiography of the brain as well as metabolic evaluation, were normal. Cytogenetic analysis was normal and mitochondrial DNA analysis revealed no deletions or mutations in the four affected family members and the grandmother. An autosomal dominant mode of inheritance is suggested by the fact that both sexes are affected in two generations.

Topics: Adult; Anticonvulsants; Child; Dystonia; Family Health; Female; Flunarizine; Genes, Dominant; Hemiplegia; Humans; Male; Neurologic Examination; Pedigree; Seizures; Syndrome

To summarize the clinical characteristics of alternating hemiplegia of childhood (AHC).. The clinical data of 13 children with AHC were analyzed. Cranial MRI, EEG, analysis of serum amino acids and urinary organic acids, measurement of plasma lactate and pyruvate levels were done in all patients. Other laboratory examinations such as magnetic resonance angio-imaging (MRA), digital subtraction arteriography (DSA) and Video-EEG were also performed in some patients.. Of the 13 patients, 12 were male, and 1 was female. The age of onset was from 2 days to 55 months (average 13.1 months). The initial symptoms were abnormal ocular movements (AOMs) consisting of ocular deviation, gaze or nystagmus in 2 cases, AOMs and dystonic posturing in 9 cases, hemiplegia in 2 cases. All patients had recurrent alternating hemiplegic episodes. The hemiplegic attacks lasted from a few minutes to 10 days. The occurrence of the attacks ranged from 8 times daily to one time every 2 months. In 10 patients the abnormal eye movements or dystonic posturing, at times, recurred intermittently during the hemiplegic attack. Choreoathetosis was present in 2 cases. Ataxia was present in 1 case; 7 patients also had the episodes of quadriplegia. During the episodes of quadriplegia, dysarthria or aphasia was present in 4 cases, dyspnea and dysphagia was present in 2 cases, respectively. Sleep could relieve both weakness and associated paroxysmal symptoms. Mental retardation was present in 9 cases, seizures in 3 cases. Except for EEG or Video-EEG was abnormal in 3 patients, other laboratory investigations were normal in all patients. Twelve patients received flunarizine therapy. Flunarizine reduced the severity, duration, or frequency of hemiplegic attacks in 8 patients.. The results suggest that AHC is characterized by frequent episodes of alternating hemiplegia with extrapyramidal symptoms and mental retardation, flunarizine is effective in treating some AHC patients.

Topics: Anticonvulsants; Child, Preschool; Electroencephalography; Female; Flunarizine; Hemiplegia; Humans; Infant; Infant, Newborn; Intelligence Tests; Magnetic Resonance Imaging; Male; Treatment Outcome

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.

Topics: Adolescent; Adult; Benzodiazepines; Calcium Channel Blockers; Central Nervous System; Child; Child, Preschool; Chloral Hydrate; Drug Administration Schedule; Female; Flunarizine; Hemiplegia; Humans; Japan; Male; Retrospective Studies; Surveys and Questionnaires; Treatment Outcome

We present our analysis of 44 patients with alternating hemiplegia of childhood. The clinical course usually consisted of three phases. The first was dominated by abnormal eye movements and dystonic episodes, the second by hemiplegic spells and psychomotor regression, and the third by persistent developmental delay and fixed neurologic deficits. The age of onset was 0-54 months (mean = 7.9 +/- 13 months). The presenting signs included abnormal ocular movements in 65%, dystonia in 60%, and hemiplegia in 32%. Patients with an early onset of the disorder and an early appearance of hemiplegic spells faired the poorest developmentally. Developmental delay was present in 91%, ataxia in 68%, choreoathetosis in 50%, and seizures in 18%. Laboratory investigations suggested mitochondrial abnormalities and cerebrovascular dysfunction in several patients. Numerous therapies were largely ineffective. Flunarizine reduced the duration, severity, and frequency of the hemiplegic attacks in 78%. Patients who received flunarizine did not differ developmentally from those who did not. Our data suggest that flunarizine does not adversely affect and may favorably influence the outcome in patients with alternating hemiplegia of childhood. Additionally, the occurrence of autosomal-dominant cases of the syndrome, although rare, suggests that, in addition to mitochondrial dysfunction, genetic factors may be important.

Topics: Adolescent; Adult; Anticonvulsants; Child; Child, Preschool; Developmental Disabilities; Female; Flunarizine; Hemiplegia; Humans; Infant; Male; Periodicity; Retrospective Studies; Treatment Outcome

Topics: Child; Diagnosis, Differential; Electroencephalography; Flunarizine; Functional Laterality; Hemiplegia; Humans; Migraine Disorders; Mitochondrial Encephalomyopathies; Moyamoya Disease; Prognosis; Tomography, Emission-Computed, Single-Photon

In infancy, two brothers developed recurrent attacks of alternating or bilateral hemiplegia arising exclusively out of sleep. The episodes were terminated by even brief sleep. Neither child had hypotonia, dystonic attacks, paroxysmal eye movement abnormalities, or other features characteristic of the now-classic form of alternating hemiplegia of childhood (AHC). The development of the brothers has so far remained normal. Both parents have a history of migraine. In the older boy, magnetic resonance spectroscopy (MRS) of muscle showed increased inorganic phosphate similar to what is found in children with AHC. In the younger brother and parents, MRS of muscle was normal. Other investigations were unrevealing. Flunarizine greatly reduced the duration of attacks. This genetically determined disorder represents a specific entity that is probably migraine-related and is easily misdiagnosed as AHC. Because of its benign course, particularly as far as mental development is concerned, it must be distinguished from classic AHC, which has a terrible prognosis.

Topics: Adult; Anti-Anxiety Agents; Anticonvulsants; Benzodiazepines; Benzodiazepinones; Clobazam; Electroencephalography; Female; Flunarizine; Hemiplegia; Humans; Infant; Magnetic Resonance Spectroscopy; Male; Migraine Disorders; Muscle, Skeletal; Phosphates; Recurrence; Sleep Wake Disorders

A patient with unusual alternating hemiplegia in childhood is reported. The frequency of hemiplegic episodes was lower than that in other reported patients. Interictal positron emission tomography revealed decreased cerebral blood flow in the left hemisphere. After cerebral angiography, postanesthetic irritability occurred which evolved into coma with hemiplegic episodes. We believe that cerebral angiography in a child with alternating hemiplegia may cause hemiplegic episodes and coma. The episodes disappeared almost completely for 6 years after treatment with flunarizine, thus indicating the benefit of the medication for the treatment of alternating hemiplegia.

Topics: Basal Ganglia; Cerebral Angiography; Cerebral Cortex; Child; Coma; Dominance, Cerebral; Electroencephalography; Epilepsy, Tonic-Clonic; Female; Flunarizine; Follow-Up Studies; Hemiplegia; Humans; Ischemic Attack, Transient; Recurrence; Regional Blood Flow; Status Epilepticus; Tomography, Emission-Computed

We report 2 children with early onset of hypotonia and frequent episodes of paroxysmal dystonia. The episodes were abolished even by brief naps. One of the children developed alternating hemiplegia in the second decade. These children seem to have a variant of the now well-recognized syndrome of alternating hemiplegia of childhood. In that disorder, episodes of alternating hemiplegia develop before the age of 18 months. This syndrome must be considered in the differential diagnosis of paroxysmal dystonia in childhood.

Topics: Adolescent; Athetosis; Brain; Child, Preschool; Chorea; Dystonia; Electroencephalography; Female; Flunarizine; Functional Laterality; Hemiplegia; Humans; Intellectual Disability; Muscle Hypotonia

Alterations in regional cerebral blood-flow, as determined by single-photon emission computed tomography (SPECT) using technetium [99mTc] hexamethyl propylenamine oxime, were studied in two children presenting with alternating hemiplegia of childhood. Both experienced hemiplegic episodes several times per month, despite marked improvement on flunarizine therapy. SPECT images of both patients revealed focal areas of decreased uptake of the radiotracer, representing impaired regional cerebral blood-flow during, as well as between, seizures. The interictal finding of localized areas of reduced tracer uptake suggest that long-lasting hypoperfusion could be the pathophysiological mechanism by which the slowly resolving hemiplegia, and ultimately the permanent multifocal neurological deficits, are produced.

Topics: Brain; Brain Diseases; Cerebrovascular Circulation; Child, Preschool; Female; Flunarizine; Functional Laterality; Hemiplegia; Humans; Intellectual Disability; Language Disorders; Male; Organotechnetium Compounds; Oximes; Technetium Tc 99m Exametazime; Tomography, Emission-Computed, Single-Photon

Alternating hemiplegia of childhood is a rare syndrome characterized by onset before 18 months of age of frequent attacks of alternating paralysis, transient ocular palsies, nystagmus, choreoathetosis, and autonomic dysfunction. We describe features of 10 patients followed for up to 27 years. The mechanism of alternating hemiplegia remains unknown but an association to migraine is suspected because of the strong family history of migraine and aura symptoms in some patients. We treated nine patients with flunarizine, a calcium channel blocker, for up to 5 years; they showed a reduction in duration of the hemiplegic attacks, but the episodes ceased completely in only one patient. With long-term follow-up, the persistent motor, movement, and cognitive deficits are more apparent. It is not certain if the flunarizine alters this course.

Topics: Adolescent; Adult; Autonomic Nervous System Diseases; Child; Child, Preschool; Electroencephalography; Female; Flunarizine; Hemiplegia; Humans; Magnetic Resonance Spectroscopy; Male; Muscles; Nystagmus, Pathologic; Organophosphorus Compounds; Recurrence; Retrospective Studies; Status Epilepticus; Syndrome

We report the familial occurrence and apparent autosomal dominant inheritance of alternating hemiplegia of childhood. The proband, a 9-year-old boy, presented with developmental retardation, rare tonic-clonic seizures, and frequent episodes of flaccid alternating hemiplegia that had been presumed to represent postictal paralysis. The hemiplegia spells, which started in his first year, did not respond to multiple antiepileptics. Between attacks, there was choreoathetosis and dystonic posturing. Father, brother, paternal uncle, and paternal grandmother had similar histories of alternating hemiplegia. Investigations included negative CT, metabolic, and coagulation studies. EEG and SPECT 99mTc exametazime scanning failed to reveal any significant slowing or any major changes in cortical perfusion during hemiplegia as compared with nonhemiplegic periods. The karyotype revealed a balanced reciprocal translocation, 46,XY,t(3;9)(p26;q34) in the patient, in all the affected living relatives, and in one apparently unaffected sibling. The asymptomatic mother had a normal karyotype. Analysis of DNA markers was consistent with the karyotype results. Both affected siblings were treated with and responded to flunarizine therapy, with a greater than 70% decrease in attack frequency. Documented flunarizine trough serum concentrations were 28.9 ng/ml in the proband and 6.6 ng/ml in his brother.

Topics: Adult; Child; Child, Preschool; Diagnosis, Differential; Electroencephalography; Epilepsy; Flunarizine; Genes, Dominant; Genetic Linkage; Hemiplegia; Humans; Karyotyping; Male; Pedigree; Polymorphism, Restriction Fragment Length; Syndrome; Tomography, Emission-Computed, Single-Photon

A case of alternating hemiplegia in a young girl is presented. The partial benefits of treatment with a calcium antagonist Flunarizine in this patient and in those reported in literature are reviewed. The onset of the disease in this girl was at three months of age with several episodes that were diagnosed as seizures; afterwards she presented, besides, repeated attacks of hemiplegia involving both sides of her body in an alternating way each time with daily frequency and hours of days of duration accompanied of bad mood and irritability as well as autonomic disturbances, oculomotor abnormalities, acquired mental retardation and residual focal neurological abnormalities. After one year of treatment with a calcium-entry blocker: Flunarizine, there was a 30% reduction in the attacks frequency as well as in its severity and stop of the progression of mental retardation. So we report the consequence of precocious diagnosis and treatment of this not well known entity whose clinical signs resemble paroxistic vascular anomalies in the brainstem territory.

Topics: Child, Preschool; Female; Flunarizine; Hemiplegia; Humans

We report the case of a 3 1/2 year old girl who had had attacks of alternating hemiplegia from the age of 6 months. Peculiar features from the etiopathogenetic angle seem to be the presence of a ring of mild stenosis of the vertebral artery on the right side, the influence of the upright posture on the onset of the attacks and perhaps also of variations in atmospheric pressure. The only drug that had some effect was flunarizine. Phenobartbital, haloperidol and nadolol had no appreciable effect.

Topics: Child, Preschool; Constriction, Pathologic; Female; Flunarizine; Hemiplegia; Humans; Posture; Radiography; Vertebral Artery

Alternating hemiplegia is an infrequent form of complicated migraine. Clinical course has similarities with seizure disorders and correct diagnosis may be difficult. We report three patients whose onset in early childhood was with general impairment, transient hemiplegia, ocular movements and vasomotor symptoms. Clinical course of alternating hemiplegia is characterized by progressive neurologic deterioration. Intermittent motor impairment is alternating in side and later during the episodic attacks headache is present. Laboratory, electrophysiologic and neuroradiologic procedures are not demonstrative. In this report we show the findings in three patients in relation to the symptoms they presented, the utility of paraclinical investigations and their response to flunarizine treatment.

Topics: Age Factors; Child, Preschool; Female; Flunarizine; Hemiplegia; Humans; Infant; Male; Migraine Disorders; Periodicity

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.

Topics: Age Factors; Child; Diazepam; Drug Tolerance; Flunarizine; Hemiplegia; Humans; Male; Neurologic Examination

In 25 rats, an intracerebral hematoma was created in the foreleg area of the motor cortex by injection of 50 microliters blood. After the lesion, 13 were treated with flunarizine and 12 with the solvent. Neurological testing was performed by measuring the running time on a rotating platform. In animals with hemiparesis, the flunarizine group (n = 7) showed a significantly (P less than 0.05) better recovery than the control group (n = 8). No significant differences occurred in animals without neurological deficits (flunarizine: n = 6, control: n = 4). So the effect of the drug is not due to a non-specific activation; it may partially cure neurological deficits caused by intracerebral hematoma.

Topics: Animals; Cerebral Cortex; Cerebral Hemorrhage; Flunarizine; Hematoma; Hemiplegia; Locomotion; Male; Rats; Rats, Inbred Strains; Time Factors

Topics: Adolescent; Female; Flunarizine; Hemiplegia; Humans; Migraine Disorders

From 6 months of age on this girl experienced frequent episodes of hemiplegia involving both sides of the body and lasting up to 8 days. The attacks were often precipitated by tonic deviation of the head and/or the eyes to one side and nystagmus. At this stage the girl used to cry. Squinting, tonic stiffening of body and extremities, and dystonic posturing also occurred. Autonomic dysfunctions such as paleness of the skin, sweating, respiratory embarrassment, tachycardia, and mydriasis were associated features of the attacks. Motor and mental development of the girl is delayed. Improvement concerning severity, duration and frequency of the attacks has been achieved by permanent treatment with flunarizine in combination with acetazolamide and acetylsalicylic acid. If the child falls asleep immediately after rectal application of chloral hydrate at the onset of an attack there is no hemiplegia after awakening.

Topics: Acetazolamide; Aspirin; Brain Ischemia; Cerebral Cortex; Child, Preschool; Chloral Hydrate; Drug Therapy, Combination; Female; Flunarizine; Hemiplegia; Humans; Migraine Disorders; Tomography, Emission-Computed

Topics: Adolescent; Flunarizine; Hemiplegia; Humans; Male; Migraine Disorders

Topics: Child; Cinnarizine; Female; Flunarizine; Hemiplegia; Humans; Piperazines; Recurrence