Thirteen subjects with trigeminal neuralgia were treated with botulinum-A neurotoxin (BoNT/A) in an open-label pilot study. After BoNT/A, visual analog scale score, surface area of pain, and therapeutic coefficient were reduced in all patients and for all branch trigeminal nerves studied. Therefore, BoNT/A is an efficient treatment. There were no major side effects. A placebo-controlled clinical trial is needed to confirm these findings.

The spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders varying in both clinical manifestations and mode of inheritance. Six different genes causing autosomal dominant SCA are mapped: SCA1, SCA2, Machado-Joseph disease (MJD)/SCA3, SCA4, SCA5, and dentatorubropallidoluysian atrophy (DRPLA). Expansions of an unstable trinucleotide CAG repeat cause three of these disorders: SCA type 1 (SCA1), MJD, and DRPLA. We determine the frequency of the SCA1, DRPLA, and MJD mutations in a large group of unrelated SCA patients with various patterns of inheritance and different ethnic backgrounds. We studied 92 unrelated SCA patients. The frequency of the SCA1 mutation was 3% in the overall patient group and 10% in the non-Portuguese dominantly inherited SCA subgroup. We found that DRPLA mutation in only one Japanese patient, who was previously diagnosed with this disease. We identified the MJD mutation in 41% of the overall patient group, which included 38 autosomal dominant kindreds of Portuguese origin; the frequency of the MJD mutation among the non-Portuguese dominantly inherited cases was 17%. These results suggest that SCA may be occasionally caused by the SCA1 mutation and rarely caused by the DRPLA mutation and that, to date, the MJD mutation seems to be the most common cause of dominantly inherited SCA. Finally, our results suggest that recessively inherited cases of SCA are not caused by the known trinucleotide repeat expansions.

RESUMO -O autor apresenta breve revisão histórica acerca do papel desempenhado por J-M. Charcot, com a sua magistral contribuição na definição clínica da doença de Parkinson. PALAVRAS-CHAVE "Para aprender a tratar uma doença, precisa-se aprender a reconhecê-la: o diagnóstico é o melhor trunfo no tratamento" J-M. CharcotA doença de Parkinson (DP) é um dos distúrbios do movimento mais encontrados na população idosa, representando até 2/3 dos pacientes que visitam os grandes centros de distúrbios do movimento em todo o mundo. A prevalência da DP tem sido estimada entre 85 e 187 casos por 100000 pessoas e a incapacidade funcional produzida pela doença é comparável à causada pelos acidentes vasculares encefálicos 1 . O diagnóstico desta enfermidade neurodegenerativa é estabelecido basicamente pelo quadro clínico característico, sem a necessidade de utilização de exames complementares para tal. Os sintomas cardinais da DP são : tremor de repouso, bradicinesia, rigidez muscular e instabilidade postural. A presença de dois destes sinais acima descritos permite o diagnóstico de Parkinsonismo, sendo o Parkinsonismo Primário ou Idiopático (DP) a causa mais frequente. Outros autores acrescentam também os sinais como a postura fletida do pescoço, tronco e membros e a presença de bloqueio motor (freezing) 1,2 . JAMES PARKINSON E A PARALISIA AGITANTECoube a James Parkinson, médico inglês, membro do colégio real de cirurgiões, nascido em 1755 e falecido em 1824, o mérito da descrição inicial da doença que hoje leva o seu nome. James Parkinson publicou muitos artigos científicos dentro da área médica e nas áreas de geologia, paleontologia e sociologia, além de ter sido considerado um reformador social para o seu tempo e um panfletário político radical, escrevendo sob o pseudônimo de "Old Hubert" [1][2][3][4]

Spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia type 2 (SCA2) and Machado-Joseph disease or spinocerebellar ataxia type 3 (MJD/SCA3) are three distinctive forms of autosomal dominant spinocerebellar ataxia (SCA) caused by expansions of an unstable CAG repeat localized in the coding region of the causative genes. Another related disease, dentatorubropallidoluysian atrophy (DRPLA) is also caused by an unstable triplet repeat and can present as SCA in late onset patients. We investigated the frequency of the SCA1, SCA2, MJD/SCA3 and DRPLA mutations in 328 Brazilian patients with SCA, belonging to 90 unrelated families with various patterns of inheritance and originating in different geographic regions of Brazil. We found mutations in 35 families (39%), 32 of them with a clear autosomal dominant inheritance. The frequency of the SCA1 mutation was 3% of all patients; and 6% in the dominantly inherited SCAs. We identified the SCA2 mutation in 6% of all families and in 9% of the families with autosomal dominant inheritance. The MJD/SCA3 mutation was detected in 30% of all patients; and in the 44% of the dominantly inherited cases. We found no DRPLA mutation. In addition, we observed variability in the frequency of the different mutations according to geographic origin of the patients, which is probably related to the distinct colonization of different parts of Brazil. These results suggest that SCA may be occasionally caused by the SCA1 and SCA2 mutations in the Brazilian population, and that the MJD/SCA3 mutation is the most common cause of dominantly inherited SCA in Brazil.

The purpose of this study was to investigate if botulinum neurotoxin type-A (BoNT/A) had a preemptive antinociceptive effect in a formalin-induced orofacial pain model (FT). To test this hypothesis, male Rattus norvegicus were injected with isotonic saline solution 0.9% or BoNT/A administered as a 40 µl bolus, lateral to their nose, at 24 hours, 8, 15, 22, 29 or 36 days pre-FT. The procedures were repeated 42 days later. Influence on motor activity was assessed through the open-field test. Pain scores corresponded to the time spent rubbing and flicking the injected area. Animals pre-treated with BoNT/A at the first protocol (8 days subgroup) showed reduced inflammatory scores (p=0.011). For the other groups no significant results were observed at any phase. Motor activity was similar in both groups. BoNT/A showed to be effective preventing inflammatory pain up to eight days after the first treatment, an effect not reproduced on the second dose administration. Key words: antinociceptive effect, orofacial pain, preemptive treatment, botulinum neurotoxin type-A.Toxina botulínica do tipo-A no tratamento preemptivo da dor trigeminal aguda: estudo pré-clínico duplo cego placebo controlado RESUMO O objetivo deste estudo foi investigar o efeito preemptivo da neurotoxina botulínica do tipo/A (NTBo/A) através de um modelo de dor orofacial induzida pelo teste da formalina (TF). Rattus norvegicus machos foram injetados no lábio superior com solução salina isotônica 0,9% (SSI) ou NTBo/A (subgrupos 24 horas, 8, 15, 22, 29 ou 36 dias) antes do TF, em dois tratamentos farmacológicos e respectivas avaliações intercalados por 42 dias. Os escores da dor corresponderam ao tempo de fricção da região injetada. Após o primeiro pré-tratamento com NTBo/A no subgrupo 8 dias os escores da fase inflamatória foram menores do que no grupo SSI (p=0,011). Todas as outras comparações não foram significativas. Nos testes de atividade motora não ocorreram diferenças entre SSI e NTBo/A. A NTBo/A pode ser considerada como tratamento preemptivo das dores orofaciais quando utilizada até oito dias antes do estímulo álgico, não havendo consistência terapêutica após um segundo tratamento. Palavras-chave: dor orofacial, efeito antinociceptivo, toxina botulínica do tipo-A, tratamento preemptivo.

Machado-Joseph disease (MJD) is a form of autosomal dominant spinocerebellar ataxia first described in North-American patients originating from the Portuguese islands of the Azores. Clinically this disorder is characterized by late onset progressive ataxia with associated features, such as: ophthalmoplegia, pyramidal and extrapyramidal signs and distal muscular atrophies. The causative mutation is an expansion of a CAG repeat in the coding region of the MJD1 gene. We have identified 25 unrelated families segregating the MJD mutation during a large collaborative study of spinocerebellar ataxias in Brazil. In the present study a total of 62 family members were genotyped for the CAG repeat in the MJD1 gene, as well as 63 non-MJD individuals (126 normal chromosomes), used as normal controls. We observed a wide gap between the size range of the normal and expanded CAG repeats: the normal allele had from 12 to 33 CAGs (mean = 23 CAGs), whereas the expanded alleles ranged from 66 to 78 CAGs (mean = 71.5 CAGs). There were no differences in CAG tract length according to gender of affected individuals or transmitting parent. We observed a significant negative correlation between age at onset of the disease and length of the CAG tract in the expended allele (r = -0.6, P = 0.00006); however, the size of the expanded CAG repeat could explain only about 40% of the variability in age at onset (r2 = 0.4). There was instability of the expanded CAG tract during transmission from parent to offspring, both expansions and contractions were observed; however, there was an overall tendency for expansion, with a mean increase of +2.4 CAGs. The tendency for expansion appeared to the greater in paternal (mean increase of +3.5 CAGs) than in maternal transmissions (mean increase of +1.3 CAGs). Anticipation was observed in all transmissions in which ages at onset for parent and offspring were known; however, anticipation was not always associated with an increase in the expanded CAG repeat length. Our results indicate that the molecular diagnosis of MJD can be confirmed or excluded in all suspected individuals, since alleles of intermediary size were not observed.
A doença de Machado-Joseph (MJD) é uma forma de ataxia espinocerebelar (AEC) de herança autossômica domi nante, que foi descrita inicialmente em pacientes norte-americanos provenientes das ilhas portuguesas dos Açores. Clinicamente essa doença é caracterizada por uma ataxia cerebelar progressiva, de início tardio e com algumas características associadas tais como: oftalmoplegia, sinais piramidais e extrapiramidais e amiotrofias. A mutação responsável é uma expansão de trinucleotídeos CAG localizada na região codificadora do gene MJD1. Como parte de um estudo colaborativo sobre AEC no Brasil, nós identificamos 25 famílias, não aparentadas, segregando a mutação MJD. Nesse artigo nós relatamos as características moleculares do trinucleotídeo CAG presente no gene MJD1 em 62 indivíduos dessas famílias com MJD e em 63 indivíduos que não apresentam a mutação MJD (126 cromossomos normai...

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Relato do caso de paciente do sexo feminino com 40 anos de idade, com quadro progressivo de diminuição de força, disfonia, disfagia, dispnéia e hiperidrose. O exame físico revelava contratura em flexão das mãos, déficit de força muscular, fasciculações, mioquimia facial e pseudomiotonia nas mãos, A eletromiografia mostrou atividade elétrica contínua em repouso. O estudo histoquímico muscular revelou atrofia de fibras do tipo II, enquanto a microscopia eletrônica mostrou dilatação importante das cisternas do retículo sarcoplasmático. O diagnóstico de síndrome de Isaacs foi firmado. Excelente resposta clínica ao emprego de carbamazepina foi observada. São discutidos e revistos vários aspectos relacionados a essa rara síndrome.