Distúrbios neurológicos associados com anticorpos anti-GAD são doenças pleomórficas, raras, de causa incerta, das quais a rigidez muscular espasmódica (SPR) é a mais conhecida. Neste estudo, descrevemos nove casos consecutivos de distúrbios neurológicos associados com a presença de anticorpos anti-GAD, incluindo nove pacientes com SPR e três casos com ataxia cerebelar. Adicionalmente, foram encontrados quatro casos com hipotireoidismo, três com epilepsia, dois com diabetes mellitus e dois casos com mioclonia axial.

Neurological disorders associated with glutamic acid decarboxylase (GAD) antibodies are rare pleomorphic diseases of uncertain cause, of which stiff-person syndrome (SPS) is the best-known. Here, we described nine consecutive cases of neurological disorders associated with anti-GAD, including nine patients with SPS and three cases with cerebellar ataxia. Additionally, four had hypothyroidism, three epilepsy, two diabetes mellitus and two axial myoclonus.

A maioria dos casos de distonia cervical (DC) são idiopáticos; injeções locais com toxina botulínica A (BoNT/A) são o tratamento de escolha. O objetivo de nosso estudo foi documentar os efeitos do tratamento a longo prazo da BoNT/A em pacientes com DC idiopática. Foram selecionados 58 pacientes com DC idiopática de março de 2001 a maio de 2002. Desses pacientes, 28 estavam disponíveis para re-avaliação após sete anos. Durante esse período, todos foram submetidos a tratamento regular com injeções de BoNT/A. As informações clínicas dos pacientes e a gravidade da DC (TWSTRS e VAS) na primeira avaliação (2001-2002) e na reavaliação (2008-2009) foram comparadas. Houve uma significante melhora motora detectada pelos resultados da escala TWSTRS, usada para analisar a gravidade clínica (19,6±6,6 e 17,7±4,8; p<0,05). Não houve melhora nos resultados referentes a dor cervical (p=0,43). Em conclusão, BoNT/A foi uma terapêutica de longo prazo efetiva e segura para DC.

Most cases of cervical dystonia (CD) are idiopathic, and focal injections of botulinum toxin A (BoNT/A) are the treatment of choice. The objective of our study was to document the effects of long-term BoNT/A treatment in idiopathic CD patients. Fifty-eight patients with idiopathic CD were recruited from March 2001 to May 2002. Twenty-eight of the subjects were available for reassessment after seven years. During this period, all had received regular treatment with BoNT/A injections. Clinical information about patients and the severity of CD (TWSTRS and VAPS) at baseline assessment (2001-2002) and follow-up (2008-2009) was compared. Significant motor improvement was detected based on TWSTRS scale scores, which were used to analyze clinical severity (19.6±6.6 and 17.7±4.8; p<0.05). There was no improvement in the severity of cervical pain (p=0.43). In conclusion, BoNT/A was a safe and effective long-term therapy for CD.

No Brasil, apenas alguns hospitais realizam terapia trombolítica para o acidente vascular cerebral isquêmico agudo (AVCiA). OBJETIVO: O objetivo deste estudo foi descrever um protocolo inter-institucional para a rápida identificação e para o tratamento trombolítico de pacientes com AVCiA em hospital público de Curitiba, PR. MÉTODO: O Serviço de Atendimento Médico de Urgência (SAMU) avaliou 433 pacientes com possível AVC durante um período de seis meses. Depois de um check list padrão, os pacientes com suspeita de AVCiA e início dos sintomas inferior a duas horas, foram avaliados no Hospital de Clínicas (HC). RESULTADOS: Sessenta e cinco (15%) pacientes preencheram os critérios propostos, porém apenas 50 pacientes (11%) foram avaliados no HC. Destes, 35 (70%) eram AVC isquêmico (AVCi), 10 (20%) eram hemorrágicos e 5 (10%) tiveram outros diagnósticos. Dos 35 pacientes com AVCi, 15 (43%) foram submetidos a trombólise IV. CONCLUSÃO: O presente estudo demonstrou que o treinamento do SAMU poderia auxiliar na otimização da terapia trombolítica em grandes cidades brasileiras. Programas permanentes de treinamento com controle de qualidade, caracterizados pela correta identificação de pacientes com AVCiA devem ser realizados nos hospitais em parceria com o SAMU para elevar as taxas de tratamento trombolítico no Brasil.

Few healthcare centers in Brazil perform thrombolytic therapy for acute ischemic stroke (AIS) patients. OBJECTIVE: The aim of this study was to describe an interinstitutional protocol for the rapid identification and thrombolytic treatment of AIS patients at a public health hospital in a large Brazilian city. METHOD: Emergency medical services (EMS) personnel evaluated 433 patients with possible stroke during a six-month period. After a standard checklist, patients with suspected AIS and symptoms onset of less than two hours were evaluated at our University Hospital (UH). RESULTS: Sixty-five (15%) patients met the checklist criteria and had a symptom onset of less than two hours, but only 50 (11%) patients were evaluated at the UH. Among them, 35 (70%) patients had ischemic stroke, 10 (20%) had hemorrhagic stroke, and 5 (10%) had other diagnoses. Of the 35 ischemic stroke patients, 15 (43%) underwent IV thrombolysis. CONCLUSION: The present study demonstrated that trained EMS workers could help to improve the rate of thrombolytic treatment in large Brazilian cities. Permanent training programs for EMS and hospital staff, with quality control and correct identification of AIS patients, should be implemented to increase appropriate thrombolytic therapy rates in Brazil.

OBJETIVO: A CYP2C9 é uma das principais enzimas do metabolismo de drogas humano e o polimorfismo observado no respectivo gene pode afetar o resultado terapêutico durante o tratamento. Neste trabalho investigamos em uma população de pacientes portadores de epilepsia a distribuição dos alelos variantes do CYP2C9 e a frequência de efeitos adversos da fenitoína tentando estabelecer uma correlação. MÉTODO: Realizamos uma análise através de uma PCR alelo específica para determinar a frequência dos alelos variantes mais comuns, CYP2C9*2 e CYP2C9*3, isolados da amostra de 100 pacientes com epilepsia. Também levantamos a frequência de reações adversas da fenitoína nestes diferentes grupos genotípicos. Os dados são apresentados na forma de média e desvio-padrão. RESULTADOS: A idade média na inclusão foi 39,6±10,3 anos (variando de 17-72 anos) e a duração da epilepsia era 26,5±11,9 anos (variando de 3-48 anos). A idade média dos pacientes no início da epilepsia era 13,1±12,4 anos (variando de 1 mês-62 anos). As frequências do CYP2C9*1 (84%), CYP2C9*2 (9%) e CYP2C9*3 (7%) foram similares a outros estudos publicados. As reações adversas da fenitoína foram frequentemente leves e ocorreram em 15% dos pacientes, sem correlação com o polimorfismo do CYP2C9 (p=0.34). CONCLUSÃO: Nossos achados indicam uma distribuição similar dos alelos variantes *2 e *3 nesta população de pacientes com epilepsia comparado a outros estudos. Esta amostra de usuários de fenitoína mostrou não haver correlação entre efeitos colaterais relacionados à droga e o tipo de alelo variante. O papel da influência do polimorfismo do CYP2C9 nos efeitos colaterais da fenitoína precisam ser melhor determinados, já que algumas evidencias da literatura e este trabalho mostraram resultados negativos.

OBJECTIVE: CYP2C9 is a major enzyme in human drug metabolism and the polymorphism observed in the corresponding gene may affect therapeutic outcome during treatment. The distribution of variant CYP2C9 alleles and prevalence of phenytoin adverse reactions were hereby investigated in a population of patients diagnosed with epilepsy. METHOD: Allele-specific PCR analysis was carried out in order to determine frequencies of the two most common variant alleles, CYP2C9*2 and CYP2C9*3 in genomic DNA isolated from 100 epileptic patients. We also analyzed the frequency of phenytoin adverse reactions among those different genotypes groups. The data was presented as mean±standard deviation. RESULTS: The mean age at enrollment was 39.6±10.3 years (range, 17-72 years) and duration of epilepsy was 26.5±11.9 years (range 3-48 years). The mean age at epilepsy onset was 13.1±12.4 years (range, 1 month-62 years). Frequencies of CYP2C9*1 (84%), CYP2C9*2 (9%) and CYP2C9*3 (7%) were similar to other published reports. Phenytoin adverse reactions were usually mild and occurred in 15% patients, without correlation with the CYP2C9 polymorphism (p=0.34). CONCLUSION: Our findings indicate an overall similar distribution of the CYP2C9 alleles in a population of patients diagnosed with epilepsy in the South of Brazil, compared to other samples. This sample of phenytoin users showed no drug related adverse reactions and CYP2C9 allele type correlation. The role of CYP2C9 polymorphism influence on phenytoin adverse reaction remains to be determined since some literature evidence and our data found negative results.

OBJECTIVE: To study tremor in patients with X-linked recessive spinobulbar muscular atrophy or Kennedy's disease. METHODS: Ten patients (from 7 families) with a genetic diagnosis of Kennedy's disease were screened for the presence of tremor using a standardized clinical protocol and followed up at a neurology outpatient clinic. All index patients were genotyped and showed an expanded allele in the androgen receptor gene. RESULTS: Mean patient age was 37.6 years and mean number of CAG repeats 47 (44-53). Tremor was present in 8 (80%) patients and was predominantly postural hand tremor. Alcohol responsiveness was detected in 7 (88%) patients with tremor, who all responded well to treatment with a β-blocker (propranolol). CONCLUSION: Tremor is a common feature in patients with Kennedy's disease and has characteristics similar to those of essential tremor.

BACKGROUND: Long-term data on the clinical follow-up and the treatment effectiveness of Wilson's disease are limited because of the low disease frequency. This study evaluated a retrospective cohort of Wilson's disease patients from southern Brazil during a 40-year follow-up period. METHODS: Thirty-six Wilson's disease patients, diagnosed from 1971 to 2010, were retrospectively evaluated according to their clinical presentation, epidemiological and social features, response to therapy and outcome. RESULTS: Examining the patients' continental origins showed that 74.5% had a European ancestor. The mean age at the initial symptom presentation was 23.3 ± 9.3 years, with a delay of 27.5 ± 41.9 months until definitive diagnosis. At presentation, hepatic symptoms were predominant (38.9%), followed by mixed symptoms (hepatic and neuropsychiatric) (30.6%) and neuropsychiatric symptoms (25%). Kayser-Fleischer rings were identified in 55.6% of patients, with a higher frequency among those patients with neuropsychiatric symptoms (77.8%). Eighteen patients developed neuropsychiatric features, most commonly cerebellar syndrome. Neuroradiological imaging abnormalities were observed in 72.2% of these patients. Chronic liver disease was detected in 68% of the patients with hepatic symptoms. 94.2% of all the patients were treated with D-penicillamine for a mean time of 129.9 ± 108.3 months. Other treatments included zinc salts, combined therapy and liver transplantation. After initiating therapy, 78.8% of the patients had a stable or improved outcome, and the overall survival rate was 90.1%. CONCLUSION: This study is the first retrospective description of a population of Wilson's disease patients of mainly European continental origin who live in southern Brazil. Wilson's disease is treatable if correctly diagnosed, and an adequate quality of life can be achieved, resulting in a long overall survival.

OBJETIVO: Comparar dois momentos diferentes da manobra de Valsalva (MV) com o uso de solução salina com sangue como meio de contraste (MC) para investigação de embolia paradoxal (EP). MÉTODO: 42 pacientes foram submetidos a protocolo padronizado de DTCc com a MV em dois momentos diferentes: [1] injeção do MC durante a MV (teste ACduranteMV); [2] injeção de MC antes da MV (teste ACpreMV). RESULTADOS: Exames positivos foram observados em 47 (56%) ACMs testes ACduranteMV e 50 (59.5%) testes ACpreMV, p=0.64. Houve uma correlação quase perfeita entre ambos os testes, r s=0.829 (95% CI 0.61-1.00, p<0.001). CONCLUSÃO: O presente estudo demonstra que não existe diferença significativa na positividade de EP pelo DTCc quando são comparados dois momentos diferentes da MV.

OBJECTIVE: To compare two different timings for the performance of the Valsalva maneuver (VM) using an infusion of agitated saline solution with blood as contrast agent (CA) to right-to-left shunt (RLS) screening. METHOD: 42 patients were submitted to a standardized contrast-enhanced transcranial doppler (cTCD) to screen for right-to-left shunt (RLS). cTCD technique was done with two different moments of the VM: [1] the CA injection during the VM (CAduringVM test); [2] the CA injection before the VM (CApreVM test). RESULTS: Positive MCA tests were observed in 47 (56%) CAduringVM tests and in 50 (59.5%) CApreVM tests, p=0.64. There was an almost perfect agreement for the positive tests between the CAduringVM and CApreVM test, r s=0.829 (95% CI 0.61-1.00, p<0.001). CONCLUSION: The present study demonstrates that there is no significant difference in the results of RLS screening by cTCD when two different moments of VM were done.

Miopatia nemalínica (NM) é uma doença congênita que leva a hipotonia e dificuldade de sugar em neonatos. Alguns casos possuem uma evolução benigna, com deformidades ósseas tardias. Nós analisamos uma série de oito pacientes com NM obtidos da análise retrospectiva de 4300 biópsias musculares. Os pacientes foram classificados como forma típica em cinco casos, forma intermediária em dois casos e forma severa em um caso. Análise histoquímica mostrou distribuição mista dos rods em todos os casos e predominância de fibras tipo I em cinco casos. Análise imuno-histoquímica mostrou expressão anormal da nebulina em todos os pacientes (quatro heterogênea e quatro ausente), expressão homogenea da desmina em quatro casos, fortemente positiva em tres e ausente em um, expressão da miosina (rápida) com padrão em mosaico em seis casos e ausente em dois casos. Não há relação específica entre a expressão destas proteínas e as formas clínicas da NM.

Nemaline myopathy (NM) is a congenital disease that leads to hypotonia and feeding difficulties in neonates. Some cases have a more benign course, with skeletal abnormalities later in life. We analyzed a series of eight patients with NM obtained from a retrospective analysis of 4300 muscle biopsies. Patients were classified as having the typical form in five cases, intermediate form in two cases and severe form in one case. Histochemical analysis showed mixed rods distribution in all cases and predominance of type I fibers in five cases. Immunohistochemical analysis showed abnormal nebulin expression in all patients (four heterogeneous and four absent), homogeneous desmin expression in four cases, strongly positive in three and absent in one, fast myosin expression in a mosaic pattern in six cases and absent in two cases. There was no specific relation between these protein expression patterns and the clinical forms of NM.

Para avaliação da segurança e eficácia do tratamento com toxina botulínica A (TB-A) na espasticidade na paralisia cerebral (PC), foram selecionadas 20 crianças com a forma diplegia espástica. Todos os pacientes receberam injeções nos gastrocnêmios e sóleos, 15 receberam doses nos adutores da coxa. A dose total variou de 70 a 140 Us (99,75±16,26 U), 7,45±2,06 U/Kg por paciente. O tratamento com a TB-A melhorou significativamente a deambulação e o padrão de marcha. Houve também significativa alteração da distância tornozelo-solo e aumento da amplitude de movimento da articulação do tornozelo. Essas mudanças estruturais dos pés se mantiveram até o final do acompanhamento. O mesmo não foi observado com parâmetros funcionais. Três pacientes apresentaram fraqueza em membros inferiores. Conclui-se que a TB-A, em uma única aplicação, é segura e eficaz. Há modificação sustentada da estrutura motora dos membros inferiores, porém mudanças funcionais são temporárias, durante o pico de ação do medicamento.

We evaluated the safety and effectiveness of botulinum toxin A (BoNT/A) in the treatment of spasticity in 20 children with spastic diplegic cerebral palsy (CP). All the patients received injections in the gastrocnemius and soleus, and 15 received injections in the adductors. The total dose varied from 70 to 140 U (99.75±16.26 U), or 7.45±2.06 U/kg per patient. The treatment improved the patients' walking and gait pattern significantly. There was also a significant alteration in the heel-ground distance and increased motion of the ankle joint. These structural changes in the feet were sustained until the end of the follow-up, although the same was not observed for the functional parameters. Three patients complained of weakness in the lower limbs. In conclusion, BoNT/A is safe and effective when used in a single session of injections and produces a sustained structural modification of the lower limbs. However, functional changes are temporary and are only observed during the peak effect of the drug.

CONTEXTO E OBJETIVO: O sinal de Lhermitte, um sinal neurológico clássico, é uma rara manifestação clínica da deficiência de vitamina B12. O objetivo foi relatar o caso de um paciente idoso com deficiência de vitamina B12, cuja manifestação clínica inicial foi a presença do sinal de Lhermitte. RELATO DO CASO: Paciente idoso com deficiência de vitamina B12, apresentou-se com disfunção cognitiva, polineuropatia periférica e ataxia sensitiva, cuja manifestação clínica inicial foi a presença do sinal de Lhermitte. Este sinal é uma das mais raras manifestações da deficiência de vitamina B12.

CONTEXT AND OBJECTIVE: Lhermitte's sign, a classical neurological sign, is a rare manifestation of vitamin B12 deficiency. The aim here was to report on a case of an elderly patient with vitamin B12 deficiency whose first clinical manifestation was the presence of Lhermitte's sign. CASE REPORT: We describe an elderly patient with vitamin B12 deficiency who presented cognitive dysfunction, peripheral polyneuropathy and sensory ataxia, and whose first clinical manifestation was the presence of Lhermitte's sign. This sign is one of the rarest manifestations of vitamin B12 deficiency.

Receptores NMDA e não-NMDA estão envolvidos na transmissão das informações nociceptivas em condições fisiológicas e patológicas. Com o objetivo de estudar a influência dos antagonistas dos receptores NMDA e não-NMDA sobre o controle de dor no sistema trigeminal utilizamos modelo de dor orofacial induzida pela formalina. Testes de desempenho motor foram também avaliados. Ratos machos da espécie Rattus norvegicus foram tratados com topiramato (T) (n=8), memantina (M) (n=8), divalproato de sódio (D) (n=8) ou solução salina isotônica (SSI) (n=10), por via intraperitoneal, 30 minutos antes dos testes com a formalina. Formalina 2.5% foram injetadas na região do lábio superior dos animais (segundo ramo do trigêmeo) induzindo comportamento em duas fases distintas: fase I (precoce ou neurogênica) (0-3 min ) e fase II (tardia ou inflamatória) (12-30 min). Para avaliação da atividade motora utilizou-se o teste do campo aberto mensurando-se a latência para o início dos movimentos, número de casas andadas, freqüência de levantamentos e tempo de imobilidade. Animais pré-tratados com M e D atenuaram a fase inflamatória do teste da formalina. O T aumenta o número de casas andadas, freqüência de levantamentos e reduz o tempo de imobilidade. Nossos resultados mostram que o antagonista NMDA é mais potente do que os antagonistas não-NMDA para o controle da fase inflamatória da dor. O topiramato entretanto aumenta a atividade motora provavelmente porque apresente propriedades ansiolíticas.

NMDA and non-NMDA receptors are involved in spinal transmission of nociceptive information in physiological and pathological conditions. Our objective was to study the influence of NMDA and non-NMDA receptor antagonists on pain control in the trigeminal system using a formalin-induced orofacial pain model. Motor performance was also evaluated. Male Rattus norvegicus were pre-treated with topiramate (T) (n=8), memantine (M) (n=8), divalproex (D) (n=8) or isotonic saline solution (ISS) (n=10) intraperitoneally 30 minutes before the formalin test. Formalin 2.5% was injected into the right upper lip (V2 branch) and induced two phases: phase I (early or neurogenic) (0-3 min) and phase II (late or inflammatory) (12-30 min). For motor behavior performance we used the open-field test and measured latency to movement onset, locomotion and rearing frequencies, and immobility time. Pre-treatment of animals with M and D only attenuated nociceptive formalin behavior for phase II. T increased locomotion and rearing frequencies and reduced immobility time. Treatment with M increased immobility time and with D reduced locomotion frequency. Our results showed that the NMDA antagonist (M) is more potent than the non-NMDA antagonists (D and T) in the control of pain in the inflammatory phase. The non-NMDA topiramate improved motor performance more than did D and M, probably because T has more anxiolytic properties.

A comunicação direita-esquerda (CDE) pode ser identificada por Doppler transcraniano contrastado (DTCc) em pacientes com forame oval patente (FOP). OBJETIVOS: Analisar o DTCc para triagem de FOP comparado a ecocardiografia transesofágica (ETEc). MÉTODO: Realizamos 45 exames de DTCc para diagnóstico de FOP e correlacionamos com os achados do ETEc. Os pacientes foram submetidos a técnica padronizada e divididos em dois grupos conforme a positividade do exame. RESULTADOS: 29 (65%) pacientes foram incluídos no grupo 1 (CDE positiva) e 16 (35%) no grupo 2 (CDE negativa). A confirmação do FOP pelo ETEc ocorreu em 28 (62%) pacientes. O DTCc apresentou sensibilidade de 92,85%, especificidade de 82,35%, valor preditivo positivo de 89,65% e valor preditivo negativo de 87,5% comparado ao ETEc para o diagnóstico de FOP. CONCLUSÃO: A técnica padronizada de DTCc possibilita a visualização de CDE em pacientes com FOP com boa correlação com o ETEc.

Right-to-left shunt (RLS) can be identified by contrast-enhanced transcranial Doppler (cTCD) in patent foramen ovale (PFO) patients. AIM: To evaluate cTCD for PFO screening comparing it to cTEE. METHOD: 45 previous cTCD performed for PFO diagnosis and correlated its findings with cTEE. Patients were submitted to a cTCD standardized technique and were divided in two groups according to RLS: Group 1, patients with a positive RLS and Group 2 when RLS was negative. RESULTS: 29 (65%) patients were included in group 1 and 16 (35%) in group 2. PFO confirmation by cTEE was performed in 28 (62%) patients. cTCD had a 92.85% sensitivity, 82.35% specificity, 89.65% positive predictive value and 87.5% negative predictive value when compared to cTEE for PFO diagnosis. CONCLUSION: Standardized technique cTCD allows for RLS visualization in PFO patients with a good correlation with cTEE and can be used as a screening test before cTEE.