Objetivo Descrever características do transtorno comportamental do sono REM (TCSR) na doença de Wilson (DW). Método Aplicação de entrevistas, vídeo-polissonografia, sonografia transcraniana (STC), ressonância magnética (RM), diário de sonhos. Resultados Descrevemos quatro casos de DW com TCSR. Três apresentaram o TCSR como primeira manifestação. Todos mostraram hiperecogenicidades mesencefálicas na STC, dois apresentaram hiperintensidades ponto-mesencefálicas na RM. Conclusão Esta é a primeira descrição do TCSR na DW. Relatamos o TCSR como um sintoma inicial da DW. Acrescentamos prova para o paralelismo entre a doença de Parkinson e DW, com relação aos fenótipos e localização das lesões cerebrais. Nas alfa-sinucleinopatias, o TCSR tem relevância prognóstica quanto à neurodegeneração. Na DW, já conhecemos a importância de diagnóstico e tratamento precoces. O TCSR na DW oferece um modelo para antecipar o tratamento desta síndrome de acometimento dos núcleos basais e tronco, vislumbrando a possibilidade de tratamento neuroprotetor para a fase “pré-clínica” da DP.

Objective To describe characteristics of REM sleep behavior disorder in Wilson’s disease. Method Questionnaire-based interviews (patients and relatives), neurological examinations, two-week prospective dream-diary, video-polysomnography, transcranial sonography, MRI. Results Four Wilson’s disease cases with REM sleep behavior disorder were described; three had REM sleep behavior disorder as initial symptom. All showed mesencephalic tegmental/tectal sonographic hyperechogenicities and two presented ponto-mesencephalic tegmental MRI hyperintensities. Conclusion This first description of REM sleep behavior disorder in Wilson’s disease in literature documents REM sleep behavior disorder as a possible presenting symptom of Wilson’s disease and adds further evidence to the parallelism of Parkinson’s disease and Wilson’s disease in phenotype and brainstem topography, which ought to be further studied. REM sleep behavior disorder has prognostic relevance for neurodegeneration in α-synucleinopathies. In Wilson’s disease, usefulness of early diagnosis and treatment are already well established. REM sleep behavior disorder in Wilson’s disease offers a possible theoretical model for potential early treatment in this extrapyramidal and brainstem paradigm syndrome, previewing the possibility of neuroprotective treatment for REM sleep behavior disorder in “pre-clinical” Parkinson’s disease.

OBJECTIVES: To evaluate predictors of the response to doxazosin, a selective alpha-adrenoceptor antagonist, when used for the treatment of lower urinary tract symptoms in men with Parkinson's disease. METHODS: In a prospective study, 33 consecutive men (mean age 59.2±7.0 years) with Parkinson's disease and lower urinary tract symptoms were evaluated. Neurological dysfunction was assessed with the Unified Parkinson's Disease Rating Scale. Urological assessment was performed at baseline and after 12 weeks of treatment with 4 mg/day of extended-release doxazosin, including symptom evaluation with the International Continence Society male short-form questionnaire, an assessment of the impact of lower urinary tract symptoms on quality of life and urodynamics. Clinical and urodynamic predictors of response were specifically evaluated. RESULTS: Compared with the score at baseline, the total International Continence Society male short-form score was reduced after doxazosin administration, from 17.4±7.5 to 11.1±6.9 (p<0.001). The impact of lower urinary tract symptoms on quality of life was also significantly reduced, from 1.8±1.1 to 1.0±1.0 (p<0.001) and the maximum urinary flow varied from 9.3±4.4 to 11.2±4.6 ml/s (p = 0.025). The severity of neurological impairment was the only predictor of the clinical response. Additionally, patients with a Unified Parkinson's Disease Rating Scale score lower than 70 had a significantly higher chance of clinical improvement with doxazosin treatment than those with higher Unified Parkinson's Disease Rating Scale scores did (RR = 3.10, 95% CI = [1.15 to 5.37], p = 0.011). CONCLUSIONS: Doxazosin resulted in the improvement of lower urinary tract symptoms and the maximum flow rate and was well tolerated in men with Parkinson's disease. The response to treatment is dependent on the severity of neurological disability.

Testes padronizados já estão disponíveis para testagem do olfato e uma versão em Português esta sendo desenvolvida para o University of Pennsylvania Smell Identification Test (UPSIT), especificamente para a população brasileira. A versão mais recente deste teste (chamada UPSIT-Br2) foi aplicada a 88 sujeitos brasileiros que não tinham história de qualquer problema neurológico ou otorrinolaringológico. Compatível com dados prévios da literatura, a performance no UPSIT-Br2 decaiu com a idade e foi inferior no genero masculino. Os resultados foram mais baixos em participantes de menor nível sócio-econômico e a relação deste achado com a falta de familiaridade para com os itens do teste não é conhecida. Apesar desta versão do UPSIT poder ser útil para o teste da função olfativa da população brasileira, a revisão de alguns itens se faz necessária para alcançar valores comparáveis aos dados normativos norte-americanos.

Standardized olfactory tests are now available to quantitatively assess disorders of olfaction. A Brazilian-Portuguese version of the University of Pennsylvania Smell Identification Test (UPSIT) is currently being developed specifically for the Brazilian population. The most recent Brazilian-Portuguese version of the UPSIT (UPSIT-Br2) was administered to 88 Brazilian subjects who had no history of neurological or otorhinolaryngological disease. UPSIT-Br2 scores decreased with age, were lower in men than in women, and were lower in subjects with lower income. The degree to which the poorer performance of subjects with lower socio-economic status reflects lack of familiarity with test items is not known. Although this version of the UPSIT provides a sensitive and useful test of smell function for the Brazilian population, a revision of some test items is needed to achieve comparable norms to those found using the North American UPSIT in the United States.

A FXTAS (síndrome de tremor e ataxia associada ao X frágil) é uma doença neurodegenerativa de início tardio que afeta principalmente homens acima dos 50 anos de idade, portadores de pré-mutação do gene FMR1. A mutação completa desse gene é responsável pela síndrome do cromossomo X frágil (SXF), a causa mais comum de deficiência mental herdada. Indivíduos afetados pela FXTAS geralmente apresentam tremor de intenção e ataxia de marcha que podem estar associados a sinais radiológicos ou neuropatológicos específicos. Outras características comumente observadas são parkinsonismo, declínio cognitivo, neuropatia periférica e disfunções autonômicas. Quase uma década após sua caracterização clínica, a FXTAS é mal conhecida por médicos no Brasil. Esta revisão apresenta o conhecimento atual sobre os aspectos clínicos, genéticos e diagnósticos da síndrome.

FXTAS (Fragile X-associated tremor and ataxia syndrome) is a late- onset neurodegenerative disorder affecting mainly men, over 50 years of age, who are carriers of the FMR1 gene premutation. The full mutation of this gene causes the fragile X syndrome (FXS), the most common cause of inherited mental retardation. Individuals affected by FXTAS generally present intention tremor and gait ataxia that might be associated to specific radiological and/or neuropathological signs. Other features commonly observed are parkinsonism, cognitive decline, peripheral neuropathy and autonomic dysfunction. Nearly a decade after its clinical characterization, FXTAS is poorly recognized in Brazil. Here we present a review of the current knowledge on the clinical, genetic and diagnostic aspects of the disease.

A toxina botulínica do tipo A foi introduzida recentemente para o tratamento das co-contrações entre os músculos biceps e triceps, que comprometem a função do cotovelo nas crianças com plexopatia braquial obstétrica. Apresentamos nossa experiência preliminar com esta abordagem. Oito crianças foram tratadas com 2 - 3 U/kg de toxina botulínica injetada nos músculos triceps (4 pacientes) e biceps (4 pacientes), divididas em 2 ou 3 sítios. Todos os pacientes submetidos a injeções no triceps apresentaram melhora persistente da flexão do cotovelo e nenhum precisou de novas aplicações após seguimento de 3 a 18 meses. Três pacientes submetidos a aplicações no biceps apresentaram melhora na extensão do cotovelo, mas nenhum adquiriu força antigravitacional e o efeito durou apenas 3 a 5 meses. Um paciente não respondeu às injeções. Nossos dados sugerem que a toxina botulínica pode ser útil no tratamento de algumas crianças com seqüelas de plexopatia braquial obstétrica.

Botulinum toxin type A was recently introduced for treatment of biceps - triceps muscle cocontraction, which compromises elbow function in children with obstetrical brachial plexopathy. This is our preliminary experience with this new approach. Eight children were treated with 2 - 3 U/kg of botulinum toxin injected in the triceps (4 patients) and biceps (4 patients) muscle, divided in 2 or 3 sites. All patients submitted to triceps injections showed a long-lasting improvement of active elbow flexion and none required new injections, after a follow-up of 3 to 18 months. Three of the patients submitted to biceps injections showed some improvement of elbow extension, but none developed anti-gravitational strength for elbow extension and the effect lasted only three to five months. One patient showed no response to triceps injections. Our data suggest that botulinum toxin can be useful in some children that have persistent disability secondary to obstetrical brachial plexopathy.

Para avaliar os efeitos a longo prazo da toxina botulínica tipo A (BTX) no tratamento do blefaroespasmo foi realizado estudo retrospectivo no Ambulatório de Distúrbios do Movimento da Clínica Neurológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo de 1993 a 2003. Um total de 379 aplicações de BTX foram administradas a 30 pacientes com blefaroespasmo. Previamente ao tratamento com toxina botulínica 63% dos pacientes utilizaram medicação oral para blefaroespasmo, mas apenas 15% referiu resposta satisfatória a este tratamento. Noventa e três por cento dos pacientes tiveram resposta significativa à primeira aplicação de BTX. Não houve decremento na resposta quando comparada a primeira à última aplicação registrada dos pacientes. Efeitos adversos, em sua maioria leves, ocorreram pelo menos uma vez durante o tratamento em 53% dos pacientes. Seis pacientes interromperam o tratamento, mas não houve nenhum caso de resistência secundária.

To evaluate the long-term effect of botulinum toxin type A (BTX) in the treatment of blepharospasm, a retrospective analysis was conducted from the patients seen at the Movement Disorders Clinic of the Department of Neurology, Hospital das Clínicas, University of São Paulo School of Medicine from 1993 to 2003. A total of 379 treatments with BTX were administered to 30 patients with blepharospasm. Sixty six per cent of the subjects had used oral medication for dystonia and only 15% of them reported satisfactory response to this treatment. Ninety three per cent of the patients showed significant improvement after the first BTX injection. There was no decrement in response when compared the first and the last injection recorded. Adverse effects, mostly minor, developed at least once in 53% of patients. Six patients (20%) discontinued the treatment but there was no case of secondary resistance.

Relatamos o caso de uma mulher de 49 anos com rara combinação de miastenia gravis e distonia cervical tratada com toxina botulínica tipo A, apresentando boa resposta e nenhuma evidência de piora do quadro miastênico. A partir dessas observações concluimos que é possível o uso de toxina botulínica na presença de doença da transmissão neuromuscular.

We report the case of a 49-year-old woman who has the rare combination of myasthenia gravis and cervical dystonia. She was treated with botulinum toxin type A with good response and no evidence of deterioration of the myasthenic symptoms. We therefore conclude that it is possible to use botulinum toxin in the presence of defective neuromuscular transmission.

Tem sido descrita na literatura a ocorrência de movimentos mioclônicos e distônicos como expressão isolada de uma condição neurológica de caráter hereditário. Para essa entidade alguns autores propõem a denominação "distonia mioclônica hereditária", enquanto outros preconizam o uso da expressão "mioclonia essencial hereditária". O presente relato refere-se a uma família em que essa peculiar associação de movimentos anormais acometia diversos membros em três gerações. O propósito é uma paciente de 14 anos com movimentos distônicos instalados aos 7 anos e mioclonias aos 13 anos, com evolução lenta e tendendo à estabilização. Não havia referência a melhora sob ação do álcool (paciente abstêmia). A história familiar mostrava outros casos semelhantes. A investigação complementar (dosagens sericas de cobre, ceruloplasmina, T3, T4, TSH; pesquisa de acantócitos; exame do LCR; tomografia e ressonância do segmento cefálico) não revelou anormalidades. O quadro foi satisfatoriamente controlado com clonazepam na dose de 3 mg/dia.

The occurrence of myoclonic and dystonic movements as an isolated expression of a neurologic condition of hereditary pattern have been scarcely described in literature. For this entity some authors proposed the denomination "hereditary myoclonic dystonia" while others prefer the use of the expression "hereditary essential myoclonus". We present a family in which this unusual association of abnormal movements affected several members in three generations. The propositus patient is a 14-year-old girl who have noticed the dystonic movements by 7 years of age and the myoclonic ones by 13 years of age, with a slow progression. There was no reference about the effect of alcohol (abstemious patient). There was a family history of similar cases. The suplementary investigation (seric dosage of cupper, ceruloplasmine, T3, T4, TSH; acanthocytes search; CSF examination; CT scan and MRI of the head) did not show any abnormality. Clonazepam was the only medication that lead to a clinical improvement, reducing both movements.

Parkinsonismo consequente a intoxicações exógenas tem sido relatado desde o início do século. Os agentes mais comumente implicados são o manganês, o monóxido de carbono e o sulfureto de carbono. No presente relato descreve-se síndrome parkinsoniana consequente a exposição aguda ao óxido de etileno. Manifestações neurológicas como neuropatia periférica e distúrbios cognitivos relacionados à exposição a este gás foram previamente descritas, porém não foi encontrada na literatura registro de parkinsonismo consequente a esse tipo de intoxicação exógena.

Ethylene oxide is a gas widely used in the production of industrial chemicals. It is also used to sterilize heat-sensitive medical supplies. Previous reports of acute and chronic exposure have described neurotoxic effects like peripheral neuropathy and cognitive impairment. We describe a pure parkinsonian syndrome following acute ethylene oxide intoxication. A 39-years-old male was referred to our Movement Disorders Clinic tor evaluation of a parkinsonian syndrome. He was acutely exposed to ethylene oxide four years before and remained comatose for three days, and gradually regained consciousness.. At that time he showed a global parkinsonian syndrome including bradykinesia, rigidity and rest tremor, with a severe motor disability; no other neurological disorders were found. The symptomatology was partially controlled with biperidene and levodopa plus carbidopa. Two years later he developed L-dopa induced dyskinesias. Four years after the intoxication he was evaluated at our clinic. General examination showed no abnormalities. Neurologic examination revealed a normal menta1 status. Motor evaluation disclosed moderate bradykinesia, rigidity and rest tremor, shuffling gait, poor facial mimic, stooped posture, and his speech was low and monotonous; deep tendon reflexes were brisk. The Hoehn-Yahr disability score was degree IV. Routine laboratory and radiological exams showed results within normal limits. The CSF examination was normal. Brain computed tomography and magnetic ressonance were normal. A trial with bromocriptine and levodopa plus carbidopa did not improve dyskinesia, and he was put on a schedule including amantadine and biperidene with improvement to grade III in Hoehn-Yahr scale. In the present case there was a clear relation between the acute exogenous intoxication and irreversible parkinsonism. No other causes for the condition were identified.

São descritos três casos d© degeneração hepatolenticular (DHL.) em que o efeito nefrotóxico da D-penicilina (DP) levou à substituição dessa droga por zinco, com resultados satisfatórios. O tempo médio de tratamento com zinco nos casos descritos foi de 2 anos e 7 meses. Com base nos dados de literatura e na experiência com esses pacientes, os autores consideram que os sais de zinco podem ser uma alternativa para o tratamento da DHL quando a DP determina o aparecimento de efeitos colaterais graves que levam à sua retirada definitiva.

Three patients with symptoms and signs of hepatolenticular degeneration (HLD) who developed serious renal side effects of D-penicillamine (DP) had their therapeutic schedule changed to zinc. Patient 1, a 55 year-old man had been well until 12 years old, when skeletal changes (osteomalacia) due to tubular renal disturbance began. His diagnosis of HLD had first been established at age of 32 when he presented with «wing-beat» tremor. He was then begun on DP and his neurological symptons resolved within one year of initiating therapy but skeletal abnormalities remained unchanged as a sequel. During the next 22 years the patient was continued on DP therapy but with poor compliance. Then the reapperance of his neurological manifestations occurred several times. By the age of 53, after one year without therapy, his neurological status has worse. DP was reinstituted but some weeks later his renal laboratorial parameters became serevely affected. DP was discontinued and zinc sulfate (220mg three times daily) was introduced. On this therapeutic regimen his renal laboratorial parameters returned to previous level after one month. Within one year on this therapeutic regimen neurological manifestations were resolved. After 31 months on zinc treatment he remains neurologically asymptomatic and his renal function is satisfactory. Patient 2, a 41 years old woman had been her diagnosis of HLD at age of 20, when following the diagnosis of the disease in her old brother, she was found to have the laboratorial features of HLD and bilateral Kayser-Fleischer rings. DP treatment was recommended at that time but she quitted the follow-up. When she. was 23, an esophageal variceal bleeding occurred. At the age of 30 she started DP treatment. During 9 years the patient, under regular use of the drug remained assymptomatic. At the age of 39 she developed acute renal failure due to penicillamine-induced immune complex nephropathy. DP was then stopped and prednisone introduced. After 4 months, as renal function returned to normal, prednisone was discontinued and zinc sulphate (220mg three times daily) introduced. She remained asymptomatic for 38 months. By the age of 41 a relapse of renal manifestations occurred, and she died months later. Patient 3, a 20 year-old man developed hemolytic anemia as the single manifestation of HLD at 16. DP was introduced with excellent results. Neverthless, 4 months later, with the appearance of severe renal side--effects, this drug was replaced by zinc sulphate (220mg three times daily). After 11 months under this therapeutic schedule he was hematologically asymptomatic but an epigastric distress appeared. Zinc sulphate was discontinued and zinc acetate (170mg three times daily) was introduced. Since that time, after 30 months of treatment with zinc, he remains asymptomatic and Kayser-Fleisher rings disappeared. A review of zinc salts therapy of HLD is presented and discussed.

Foi avaliada a evolução neurológica, sob tratamento, de 76 casos de degeneração hepatolenticular. Dos 76 casos, 59 (77,6%) apresentariam melhora do quadro neurológico ou mantiveram-se assintomáticos, 8 (10,6%) permaneceram inalterados e 9 (11,8%) pioraram. Os principais fatores relacionados a resultados insatisfatórios foram: duração de tratamento insuficiente para permitir reversão de distúrbios neurológicos, uso irregular da medicação e predomínio de manifestações distônicas no quadro neurológico.

A series of 76 patients with hepatolenticular degeneration (HLD) followed up at the Hospital of the University of São Paulo Medical School between 1963 and 1988 have been studied focusing the evolution under treatment of neurological features. The assessment of neurological symptoms included 12. specific items, and it was made by a scoring system ranging from 0 to 3 (absent, mild, moderate and severe). Global score varied between 0 to 36. A functional disability scale (0, normal; 1, mild; 2, moderate; 3, severe) was also adopted. All patients received D-penicillamine but three of them developed serious renal toxic side-effects, and this drug was replaced by zinc (sulphate or acetate). Fifty-nine patients (77.6%) improved, 8 (10.6%) remained unchanged, and 9 (11.8%) got worse. The main features related to bad results were poor compliance, predominance of dystonic symptoms, and short time treatment (death due hepatic complications). Eight patients (10.5%) developed transient worsening of neurological symptoms during the first weeks of treatment. Three patients who have D-penicillamine replaced by zinc salts presented satisfactory evolution. From them, only one had neurological symptoms. Death due to infectious complications related to severe motor disability occurred in three patients, representing only 10.7% of fatal evolution.

Descreve-se o caso de paciente com síndrome parkinsoniana à direita, associada a disfunções cognitivas e síndrome de hipertensão intracraniana. A tomografia de crânio e o estudo angiográfico de vasos intracranianos demonstraram a presença de volumoso processo expansivo fronto-temporal esquerdo. A eletromiografia revelou tremor de repouso com frequência de 4 a 6 ciclos por segundo. A paciente foi submetida a ressecção cirúrgica da massa tumoral, cujo exame histológico revelou tratar-se de meningioma. A evolução pós-operatória foi excelente e após dois meses todas as anormalidades neurológicas haviam desaparecido. Um ano após a remoção do tumor a paciente permanecia assintomática sem uso de qualquer medicação. São discutidos aspectos fisiopatológicos do parkinsonismo por processo expansivo e as particularidades do presente caso são analisadas em confronto a dados da literatura.

We are presenting an uncommon case of cerebral tumor whose major manifestation was parkinsonism. The patient was a 50-year-old woman presented with a 5-month history of tremor of the right hand, particularly at rest, and headache. On neurological examination of March, 1987 there were: slight right-sided hemiparesis with symmetrical hiperreflexia; discrete bradykinesia in combination with cogwheel rigidity also on the right-side; resting tremor of the right hand; and bilateral papilledema. The neuropsycho-logycal examination disclosed: nominative aphasia, impaired recent memory and right-left disorientation. The computed tomography showed a large, left frontotemporal tumor. Angiograms of the left internal and external carotid arteries revealed a tumor blush in the left frontotemporal region supplied by a enlarged middle meningeal artery. An electromyogram revealed a 4-6 HZ tremor on right hand. A course of treatment with dexametasone 16mg/day and levodopa plus benzerazine (500mg/day) was unsuccessful. A left fronto-temporo-parietal craniotomy was performed and an attached sphenoid wing tumor was mtacroseopically completely removed. Microscopy indicated that the tumor was a meningioma. Postoperativelly, the patient made an uneventful recovery. After two weeks, her right-sided palsy and parkinsonism had disappeared, and neuropsyehologyeal deficits improved. Two months later there was no abnormalities on neurological and neuropsyehologycal examination. It was concluded that the parkinsonism was caused by mechanical pressure on the basal ganglia.

Distúrbios do movimento, geralmente de tipo distónico, têm sido relatados em heterozigotos para doença de Wilson (DW). O presente relato assinala a presença em uma mesma família de heterozigoto para DW com quadro distónico e sua sobrinha com quadro clássico de DW. Discutem-se as peculiaridades dessa família, comparando-se aos dados da literatura, bem como os possíveis mecanismos etiopatrogênicos envolvidos.

Movement disorders, mostly dystonia, sometimes occur in heterozygotes for Wilson's disease (WD). A patient with metabolic abnormalities suggestive of heterozigose for WD and dystonia is reported. His niece showed the typical neurological and metabolic abnormalities of WD. This rare coincidence and the etiopathogenic mechanisms involved are discussed .