Mutação missense de novo patogênica c. 2415C G (p. Asp805Glu) no gene ATP1A3 em paciente com hemiplegia alternante da infância com resposta favorável ao cloridrato de biperideno / A de novo missense pathogenic mutation c.2415C> G (p.Asp805Glu) in ATP1A3 gene in a patient with alternating hemiplegia of childhood with favorable response to biperiden hydrochloride

A Hemiplegia Alternante da Infância é um distúrbio neurológico grave e uma doença rara (1 em cada 100.000 recém-nascidos), caracterizado por ataques repetidos transitórios de hemiplegia episódica ou tetraplegia que podem durar minutos a horas, acompanhados por outros sintomas paroxísticos como anormalidades oculomotoras e autonômicas, distúrbios do movimento como ataxia, comprometimento cognitivo progressivo, convulsões, distonia e coreia. Os tratamentos atuais são amplamente sintomáticos. Neste relato de caso, apresentamos paciente do sexo feminino, 18 anos, na qual aos 10 meses apresentou o primeiro episódio aparente de crise convulsiva com versão ocular. O eletroencefalograma e tomografia computadorizada não revelaram anormalidades e foram administradas diversas medicações como fenobarbital, carbamazepina, valproato de sódio, topiramato, dicloridrato de flunarizina, clonazepam, cipro-heptadina e pizotifeno, todos sem resultado. Devidos aos sintomas extrapiramidais, paciente passou a utilizar biperideno, apresentando não só melhora da distonia, mas também no número de crises hemiplégicas. Aos 13 anos, ela foi diagnosticada com Hemiplegia Alternante da Infância na mutação patogênica missense de novo c.2415C G (p.Asp805Glu) no gene ATP1A3 apresentando boa resposta ao tratamento com cloridrato de biperideno. (AU)

Alternating hemiplegia of childhood is a severe neurological disorder and a rare disease (1 in 100,000 newborns), characterized by repeated transient attacks of episodic hemiplegia or tetraplegia that can last minutes to hours, accompanied by other paroxysmal symptoms such as oculomotor and autonomic abnormalities, movement disorders such as ataxia, progressive cognitive impairment, seizures, dystonia, and chorea. Current treatments are largely symptomatic. In this case report, we present a female patient, 18 years old, who presented the first apparent episode of seizure with ocular version at ten months of age. The electroencephalogram and CT scan revealed no abnormalities, and several medications such as phenobarbital, carbamazepine, sodium valproate, topiramate, flunarizine dihydrochloride, clonazepam, cyproheptadine and pizotifen were administered, all without result. Due to the extrapyramidal symptoms, the patient started using biperidene, showing improvement in dystonia and the number of hemiplegic seizures. At age 13, she was diagnosed with Alternating hemiplegia of Childhood in the pathogenic missense de novo mutation c.2415C>G (p.Asp805Glu) in the ATP1A3 gene showing a good response to treatment with biperidene hydrochloride. (AU)

Successful Management of Clozapine-induced Akathisia with Gabapentin Enacarbil: A Case Report

The management of clozapine (CLZ)-induced adverse events affects patient prognoses. Akathisia is a relatively rare adverse event related to CLZ administration and thus the management of this syndrome is not well established. Here, we report a case of treatment-resistant schizophrenia wherein CLZ-induced akathisia was successfully managed with gabapentin enacarbil (GE). The patient was a 39-year-old woman who had been treated with atypical antipsychotics other than CLZ for three years with poor tolerability. Initiation of CLZ (400 mg/day) attenuated her psychotic symptoms, but was followed by moderate akathisia. Neither benzodiazepines nor biperiden improved the akathisia; however, akathisia was finally diminished with co-administration of GE. GE facilitated a dosage increase in CLZ (450 mg/day) for the improved management of pyschotic symptoms, and thus indirectly contributed to treatment of the patient’s schizophrenia. We suggest that GE is a useful candidate for the management of CLZ-induced akathisia. The improved management of treatment-induced akathisia and other adverse events can extend the potential application of CLZ for treatment-resistant schizophrenia.

Actualización en enfermedad con cuerpos de Lewy / Update in Lewy body disease

La enfermedad con cuerpos de Lewy incluye 2 entidades que podrían ser consideradas variantes clínicas de una misma patología: la demencia con cuerpos de Lewy y la demencia en enfermedad de Parkinson. Con la finalidad de describir correctamente lo que sucede en la evolución de la enfermedad se divide el cuadro en etapa prodrómica y de demencia propiamente dicha. La primera está clínicamente representada por aquel período en el cual, si bien el paciente exhibe algunos signos y síntomas propios de la enfermedad, no reúne criterios de demencia. A pesar de ser difícil de definir y por carecerse todavía de contundentes datos clínicos y biomarcadores, se caracteriza principalmente por deterioro leve selectivo en función atencional ­ visuoespacial, trastorno del sueño REM y disautonomía‒. La segunda etapa está claramente caracterizada en los criterios de consenso del año 2005. Recientemente hemos publicado la validación de un instrumento llamado ALBA Screening Instrument, que permite diagnosticar con alta sensibilidad y especificidad la enfermedad aun en etapas tempranas y diferenciarla de otras patologías semejantes. La tomografía por emisión de positrones (PET) para transportador de dopamina es el procedimiento de referencia (gold standard) del diagnóstico. El tratamiento sintomático con anticolinesterásicos y neurolépticos atípicos favorece una buena evolución de la enfermedad y es fundamental tener en cuenta evitar medicamentos que pueden dañar gravemente a los pacientes como los anticolinérgicos y antipsicóticos típicos. Los avances en el diagnóstico y la difusión del impacto de esta enfermedad en la población contribuirán a generar mayores esfuerzos de investigación para hallar un tratamiento eficaz, preventivo o curativo o de ambas características. (AU)

Lewy body disease includes 2 entities that could be considered clinical variants of the same pathology: Dementia with Lewy bodies and Parkinson's disease Dementia. Two stages of the disease are described in this review, a prodromal stage and one of explicit dementia. The first one is clinically represented by that period in which, the patient exhibits some typical features of the disease, but not dementia criteria. Despite being difficult to define the prodromal stage and that strong clinical data and biomarkers are still lacking, there is evidence to characterize it mainly by mild selective impairment in attention and visuo-spatial function, REM sleep disorder and dysautonomia. The second stage is clearly characterized in the known consensus criteria of 2005. We have recently published the validation of an instrument called ALBA Screening Instrument which showed a high sensitivity and specificity for diagnosis of the disease even in the early stages. It´s useful to differentiate the disease from other similar pathologies. Positron Emission Tomography for dopamine transporter is the gold standard of diagnosis in life. Symptomatic treatment with anticholinesterases and atypical neuroleptics help patients in their evolution of the disease. Anticholinergics and typical antipsychotics are agents to avoid in the treatmen of the disease because can severely damage patients. Future advances in the diagnosis and dissemination of the knowledge of the disease will contribute to generate greater research efforts to find an effective preventive and / or curative treatment. (AU)

Aripiprazole-induced Tardive Dyskinesia in 13 Years Old Girl Successfully Treated with Biperiden: A Case Report

In the last years second-generation antipsychotics are increasingly prescribed in the pediatric population for the treatment of several psychiatric disorders. Among the long term adverse effects, extrapyramidal symptoms (EPS) are less reported compared to first-generation antipsychotics. Tardive dyskinesia (TD) is a iatrogenic rare syndrome characterized by persistent slow writhing and sudden involuntary movements mainly involving the oral-buccal-lingual area with masticatory movements. We report a young girl with mood disorders accompanied by mild intellectual disability and behavioral problems who had TD after treatment with Aripiprazole, which responded to Biperiden therapy.

Schizophrenia-Like Psychosis and Dandy-Walker Variant Comorbidity: Case Report

Dandy-Walker variant is a developmental malformation consisting of cerebellar hypoplasia and cystic dilatation of the fourth ventricle. Previous research has proposed a possible role for the cerebellum in cognition and in schizophrenia. In this paper we report a schizophrenia-like psychotic disorder in a 30 year-old woman with Dandy-Walker variant. The patient was treated with risperidone 6 mg/day, biperiden 4 mg/day and risperidone depot 50 mg injections fortnightly, and most of the symptoms were ameliorated within 2 months. The similar cognitive profile to populations with cerebellar pathology and rarity of the condition strongly suggests that there may be direct relationship between cerebellar pathology and appearence of psychotic symptoms.

[Effect of Ginkgo biloba, risperidone and biperiden regimen in chronic schizophrenia]

Schizophrenia is a disorder characterized by a chronic recurrent course. Despite the availability of an ever-expanding range of typical and atypical antipsychotics, a substantial proportion of patients with schizophrenia show a partial or total lack of response to antipsychotic monotherapy. This study was done to evaluate the clinical effects of Ginkgo biloba as an adjunct to the Risperidone and Biperiden in the treatment of chronic schizophrenic patients. This randomized clinical trial study was carried out on 60 chronic schizophrenic patients in Sina hospital Shahrekord, Iran during 2009-10. Schizophrenia was diagnosed by DSM-IV-TR criteria. Subjects were randomly divided into intervention and control groups. Two groups were matched according to the age, sex, education, duration of illness. Patients in interventional group received Risperidone up to 6mg/day, Biperiden 4mg/day and Ginkgo biloba 240 mg/day for 12 weeks. The control group received Risperidone up to 6mg/day and Biperiden 4mg/day for 12 weeks. The scales for assessment of positive symptoms [SAPS] and assessment of negative symptoms [SANS] were recorded in prior, 6th and 12th weeks. Data analyzed by using SPSS-15 and student t-test. The mean score of positive symptoms were 55.7 +/- 2.1 and 74.4 +/- 2.3 in interventional and control groups, respectively [P<0.05] after 12 weeks. The mean score of negative symptoms were 63 +/- 1.3 and 69.3 +/- 1.8 in interventional and controls, respectivley [P<0.05] after 12 weeks. This study suggested that the use of Ginkgo biloba as an adjunct to Respridone and Biperiden was more effective than Risperidone with Biperiden regimen improving psychological condition of chronic schizophrenic patients

Adicción a biperideno y síndrome anticolinérgico: a propósito de un caso / Biperiden addiction and anticholinergic syndrome: a case report

Se reporta el caso de un paciente de 46 años de edad, con diagnóstico de esquizofrenia, en tratamiento desde los 26 años, con trifluoperazina y decanoato de flufenazina y uso concomitante de biperideno por los efectos adversos, que desarrolló dependencia al biperideno llegando a tomar, en la última semana antes de su hospitalización 14 mg diarios. El día de su ingreso tomó 20 mg, desarrollando un cuadro compatible con síndrome anticolinérgico, que se complicó con hiponatremia severa, acidosis metabólica con alcalosis respiratoria, leucocitosis, fiebre y elevación de la creatinfosfoquinasa, por lo que la impresión diagnóstica inicial fue de síndrome neuroléptico maligno. Su evolución fue favorable, saliendo de alta a la semana.

We report the case of a 46-year-old man diagnosed with schizophrenia, treated with trifluoperazine and fluphenazine decanoate since he was 26 years old, with concomitant use of biperiden for adverse effects. He developed dependence to biperiden, taking in the last week, prior to his hospitalization, 14 mg daily. The day of his admission he took 20 mg, developing an anticholinergic syndrome, complicated with severe hyponatremia, metabolic acidosis with respiratory alkalosis, leukocytosis, fever and creatine phosphokinase elevation, due to this he was initially focused as a neuroleptic malignant syndrome. He had a favorable outcome; being discharged one week later.

Efeitos extrapiramidais como conseqüência de tratamento com neurolépticos / Extrapyramidal side effects as a consequence of treatment with neuroleptics

Objetivo: Identificar a ocorrência de efeitos extrapiramidais (EPS) com o uso de neurolépticos, em pacientes esquizofrênicos, bem como verificar o possível aparecimento de alucinação secundária ao tratamento dos EPS. Métodos: Trinta e nove pacientes que estiveram em tratamento com neurolépticos em uma instituição pública de atenção primária em saúde mental, localizada na região sul da cidade de São Paulo, tiveram seus dados coletados do prontuário e participação por meio de entrevistas após concordarem, voluntariamente, em fazer parte da pesquisa. Resultados: Dos 39 pacientes esquizofrênicos em tratamento com neurolépticos analisados, 85% apresentaram EPS, enquanto 69,7% receberam tratamento para estes efeitos colaterais de movimento. Foram tratados com biperideno 73,91% dos pacientes, enquanto 29,06% tiveram redução da dose do neuroléptico. Dos pacientes que receberam biperideno, 70,50% apresentaram alucinação/delírio, visão embaçada, sonolência ou deficit de memória verbal. Conclusões: Grande parte dos pacientes que receberam neurolépticos (85%) apresentou efeitos colaterais motores e estes, quando tratados com anticolinérgico de ação central (biperideno), apresentaram alucinação e/ou delírio (52,94%) – provavelmente pelo aumento da atividade dopaminérgica decorrente da redução de atividade colinérgica nas vias mesocortical e mesolímbica.

biochemical, cognitive, and psychiatric effects of anticholinergics benzhexol hydrochloride and biperiden hydrochloride in schizophrenic patients

It is estimated that 45 million people suffer from schizophrenia around the world; it is among the top ten leading causes of disability. By 2050, this number will have grown to approximately 71 million people. Mental illnesses contribute more to the global burden of disease than all cancers combined. The present study has been planned to evaluate the effect of anticholinergic parkinol [benzhexol hydrochloride] and akineton [biperiden hydrochloride] on erythrocyte acetyl cholinesterase [AChE] activity and serum activities of gamma-glutamyl transferase [GOT], alanine transaminase [ALT], aspartate transaminase [AST], and alkaline phosphatase [ALP] in schizophrenic patients treated with haloperidol, and also to study the effect of the previously mentioned two anticholinergics on both the cognitive functions and psychiatric symptoms in such patients. The study was carried out on 30 male schizophrenic patients who were divided into two main groups [group 1 and group 2] each of 15 patients of comparable age. The present results revealed that the total score of [PANSS] showed a significant decrease in all studied groups. The total score of [MMSE] showed a significant increase in all studied groups. The AChE activity didn't show any significant difference in all comparisons in all studied groups. In our study, there was a significant elevation of serum GGT, ALT, AST and ALP levels in some groups of treated patients as compared to pretreatment groups. The results obtained in our study showed a significant increase in serum GGT, ALT, AST, and ALP levels in groups treated with either [haloperidol + benzhexol hydrochloride] or [haloperidol + biperiden hydrochloride] as compared to the corresponding levels in groups treated with haloperidol only, respectively. From all results we can concluded that the biochemical parameters used in this study are useful in detecting any side effects of antipsychotic and anticholinergic drugs on liver functions. The treatment with [haloperidol + benzhexol hydrochloride] and [haloperidol + biperiden hydrochloride] are effective in decreasing the positive and negative symptoms of schizophrenia

[Clozapine induced oculogyric crisis, a case report]

Oculogyric crisis which is a dystonic reaction commonly caused by typical antipsychotics treatment of acute dystonias, rarely occurs with atypical antipsychotics like clozapine. The aim of this report was to describe a rare case of clozapine-induced oculogyric crisis successfully treated with biperiden. The patient was a 42-year-old woman with a 19-year history of schizophrenia treated with high-potency typical antipsychotics, risperidone and lithium augmentation with appropriate doses and duration. Because of poor response to prior medications, she was prescribed clozapine started with 25 mg/d and gradually titrated up to 150 mg/d. She has experienced two episodes of oculogyric crisis treated successfully with biperiden. Although low affinity of clozapine for blocking D2 dopaminergic receptors and its anticholinergic activity may explain the significantly lower incidence of dystonic reactions, they may happen in some patients and could be suppressed with biperiden. should consider dystonic reaction as a possible clozapine adverse effect and on the basis of this report, clozapine-induced oculogyric crisis may be treated successfully with biperiden

Demência reversível e quedas associadas ao biperideno / Reversible dementia and falls associated with biperiden

As drogas anticolinérgicas podem causar efeitos adversos, mais freqüentemente nos pacientes idosos. Relatamos um caso de demência reversível e quedas, associadas ao uso de biperideno. A paciente, com 82 anos, foi admitida em lar geriátrico devido a quedas freqüentes no domicílio, acentuado déficit cognitivo, tremores de extremidades ao movimento e perda de autonomia. Na verdade, era portadora de tremor essencial, que foi confundido com doenca de Parkinson e tratado com biperideno; posteriormente, desenvolveu déficit cognitivo que foi erroneamente diagnosticado como demência do tipo Alzheimer. Após submeter-se à avaliacão especializada, foi suspensa a droga anticolinérgica e houve reversão completa do quadro demencial; o tremor essencial foi controlado com uso de propranolol. Ao avaliar um paciente com déficit cognitivo, o clínico deve descartar possíveis causas de demência reversível, em especial, o grupo das iatrogênicas.

Acantosis Nigricans de etiología benigna / Acanthosis nigricans of benign etiology

Esta comunicación tiene por objeto presentar un caso de Acantosis nigricans de etiología poco frecuente. La misma se caracteriza por la presencia de placas hiperpigmentadas y de tacto verrugoso aterciopelado, distribuidas simétricamente en áreas de flexión. Estas lesiones pueden ser manifestación de patologías benignas o acompañar a distintas neoplasias, constituyendo en este último caso un síndrome paraneoplásico. El caso que se presenta corresponde a un cuadro de Acantosis nigricans de etiología benigna poco frecuente.

Haloperidol, biperideno e parkinsonismo / Haloperidol, biperiden and parkinsonism

O autor fez uma extensa revisäo bibliográfica sobre os neurolépticos, em especial o haloperidol, bem como sobre as reaçöes extrapiramidais, com atençäo principal ao parkinsonismo, com descriçäo de quadros e tratamentos indicados

Rehabilitación en la enfermedad de Parkinson: enfoque multidisciplinario / Rehabilitation in Parkinson's disease: a multidiscipline focus

De manera prospectiva y en forma conjunta con la Clínica de Discinesias, el Servicio de Rehabilitación y Neuropsicología Experimental, estudiamos a un grupo de 30 pacientes con Enfermedad de Parkinson (EP) en estadio I a III de la clasificación de Hoehn y Yahr, se realizó un programa de rehabilitación física abarcando aspectos motores, psicológicos y ambientales, con participación de la familia y/o cuidadores. Al analizar los resultados, se obtuvo mejoría, estadísticamente significativa en la marcha, coordinación, equilibrio y postura así como en las actividades cotidianas; el aspecto motor tuvo cambios positivos, aunque ligeramente menor que los primeros. El estado de ánimo de los pacientes y la participación también mejoró

Parkinsonismo induzido pela flunarizina: a propósito de um caso / Parkinson disease induced by flunarizine: apropos of a case

Os autores registram o caso de uma paciente com parkinsonismo induzido pela flunarizina. Ressaltam um aspecto importante, relacionado ao tremor, que assumia características wilsonianas quando realizava a prova índice-nariz. A depressäo foi sintoma importante. A cura se efetivou pela retirada da droga e pelo uso de levedopa e de tremaril por período de três meses

Electroconvulsive therapy in Parkinson's disease

Para evaluar el efecto de la terapia electroconvulsivante (TEC) en pacientes con enfermedad de parkinson, Nosotros condujimos un estudio abierto con un curso de siete días de TEC en seis pacientes con enfermedades de parkinson idiopática. El deterioro motor mejoró en todos los casos durante TEC. Esta mejoría fue sostenida en tres pacientes después de 30 días, y persistió hasta el día 60 en un paciente; los registros de depresión mejoraron en cuatro pacientes y los niveles séricos de prolactina estuvieron elevados con cinco pacientes durante la TEC, disminuyendo establemente después. La respuesta a la TEC observada en las valoraciones motoras, congnoscitivas o afectivas pereció que era independiente una de otra. La mejor respuesta en la ejecución motora se observó en aquellos pacientes con una evolución más corta de la enfermedad y etapas más bajas de discapacidad. El método de TEC utilizado en este estudio fue seguro y evitó la apnea o las contracciones musculares. Nosotros concluímos que la electroterapia perece que induce una respuesta favorable aunque afímera en la enfermedad de parkinson. Sin embargo, se deben de hacer estudios controlados a largo plazo. Otros métodos de electroestimulación más selectivos de vías dopaminérgicas se deben de investigar.

L-dopa, biperideno e excreçäo sebácea na doença de Parkinson

A excreçäo sebácea frontal de 47 parkinsonianos "de novo" antes e após tratamento com anticolinérgico (biperideno), levodopa + IDAA e bromocriptina foi avaliada pelo método do ácido ósmico. Outros 100 parkinsonianos sob terapêutica crônica com biperideno, levodopa + IDAA ou associaçäo de ambos foram avaliados. Parkinsonianos "de novo" do sexo masculino apresentam valores de excreçäo sebácea significativamente mais elevados em relaçäo `as mulheres. Verificou-se que biperideno näo foi eficaz em reduzir o grau de excreçäo sebácea. Já, em relaçäo a L-dopa + IDAA constatou-se que a droga foi efetiva em reduzir o grau de excreçäo sebácea (NC e TRE) tanto no sexo masculino quanto no feminino. Em relaçäo `a bromocriptina (10mg/dia) também constatou-se que houve reduçäo da excreçäo sebácea no sexo masculino. Correlaçäo significante positiva foi verificada entre o NC, tremor, bradieinesia, hipertonia, alteraçöes da marcha e postura e incapacidade funcional, entre parkinsonianos do sexo masculino e faixa etária 50-59 anos, no período pré-tratamento. Após o período de tratamento näo mais havia correlaçäo entre excreçäo sebácea e as manifestaçöes neurológicas da doença de Parkinson. Entre parkinsonianos sob terapêutica crônica verificou-se correlaç-äo positiva e significante entre excreçäo sebácea e bradicinesia. O grau de excreçäo sebácea de parkinsonianos "de novo" sem tratamento näo difere do grau daqueles sob tratamento crônico, exceçäo feita a parkinsonianos com idade >= 60 anos, em que verificou-se maior ggrau de exreçäo sebácea (NC e TRE) em relaçäo ao mesmo sexo e faixa etária, sem tratamento. L-dopa + IDAA foi eficiente em reduzir o grau de excreçäo sebácea de parkinsonianos "de novo", tornando-a...

Síndrome neuroléptica maligna: relato de dois casos / Neuroleptic malignant syndrome: report of 2 cases

Os autores fazem um relato sobre a síndrome neuroléptica maligna, baseados na bibliografia existente. Descrevem dois casos desta síndrome com boa evoluçäo, reforçam a necessidade de conhecimento dos efeitos colaterais dos neurolépticos, para que um uso mais judicioso deste seja feito, assim como o diagnóstico precoce destas reaçöes adversas, evitando em muitos casos a morte de pacientes

Tratamiento farmacológico de la conducta agresiva; estudio de un caso / Pharmacological treatment of aggressive behavior: one case study

Se estudia un paciente esquizofrénico con conducta agresiva. En él se evalúan, doble ciego, cuatro esquemas terapéuticos utilizado trifuoperazina, carbamazepina, biperideno y placebo. Los resultados se aprecian en función de criterios experimentales y terapéuticos. Se utilizan la escala Breve de evaluación Psiquiátrica, la de Impresión Clínica Global y la de Agresividad. Se considera la agresividad como variables independientes en un diseño experimental de caso único. El control de la conducta agresiva se observa cuando la trifluoperazina es administrada sola. Se evidenciaron diferencias estadísticamente significativas en relación con los esquemas terapéuticos