Visual losses in early-onset and late-onset Parkinson's disease.

Patients with Parkinson's disease (PD) manifest visual losses. However, it is not known whether these losses are equivalent in both early-onset (EOPD) and late-onset (LOPD) patients. We evaluated contrast sensitivity and color vision in EOPD and LOPD patients and in age-matched controls. Losses occurred in both patient groups but were more pronounced in EOPD, consistent with the notion that non-motor symptoms are affected by age of symptom onset. More studies of visual function in EOPD and LOPD patients are needed to understand how aging is related to the pathophysiology of non-motor PD symptomatology. This would permit earlier diagnosis and, perhaps, better management of the disease.

Olfactory heterogeneity in LRRK2 related Parkinsonism.

LRRK2 mutations can cause familial and sporadic Parkinson's disease (PD) with Lewy-body pathology at post-mortem. Studies of olfaction in LRRK2 are sparse and incongruent. We applied a previously validated translation of the 16 item smell identification test from Sniffin' Sticks (SS-16) to 14 parkinsonian carriers of heterozygous G2019S LRRK2 mutation and compared with 106 PD patients and 118 healthy controls. The mean SS-16 score in LRRK2 was higher than in PD (p < 0.001, 95% CI for ß = -4.7 to -1.7) and lower than in controls (p = 0.007, 95% CI for ß = +0.6 to +3.6). In the LRRK2 group, subjects with low scores had significantly more dyskinesia. They also had younger age of onset, longer disease duration, and reported less frequently a family history of PD, but none of these other differences reached significance. Odor identification is diminished in LRRK2 parkinsonism but not to the same extent as in idiopathic PD.

PINK1 mutations in a Brazilian cohort of early-onset Parkinson's disease patients.

Data on the frequency of PINK1 mutations in Brazilian patients with early-onset Parkinson's disease (EOPD) are lacking. The aim of this report was to investigate mutations of the PINK1 gene in a cohort of Brazilian patients with EOPD. Sixty consecutive familial or sporadic EOPD patients were included. All eight PINK1 exons and exon-intron boundaries were analyzed. We did not find any pathogenic mutation of PINK1 in our cohort. Single Nucleotide Polymorphisms (SNP) were identified in 46.7% of the patients and in 45.9% of controls (P = 0.9). The SNPs identified in our patients had already been described in previous reports. The results of our study support the hypothesis that mutations in PINK1 may not be a relevant cause of EOPD. In Brazil, if we consider only EOPD patients, it seems that parkin and LRRK2 mutations are more common.

Genetic and environmental findings in early-onset Parkinson's disease Brazilian patients.

Parkinson's disease (PD) etiology has been attributed both to genetic and environmental factors. In this study, we investigated Brazilian early-onset PD (EOPD) patients for mutations in PARK2 and PARK8, exposure to environmental factors and possible correlations between PARK2 polymorphisms, environmental exposure, and disease age of onset. We enrolled 72 EOPD index patients and 81 healthy volunteers. Both groups were investigated for environmental exposure. EOPD patients were screened for PARK2 and PARK8 mutations. PARK2 coding polymorphisms Ser167Asn and Val380Leu were investigated in both groups. Mutations were present in 18% of the patients and in 32% of those with a positive family history. PARK2 mutations represented 12.5% and PARK8 mutations accounted for 5.5% of the mutations. A novel PARK2 mutation (D53X) was identified in 2 patients. A positive correlation was found between EOPD and well water drinking. In patients exposed to well water, a later age of onset was observed for those who carried at least one PARK2 380Leu allele. PARK2 mutations have an important role in EOPD Brazilian patients and PARK8 might be the second most important disease causing gene in this group. Well water drinking exposure represents a risk factor for EOPD and the PARK2 coding polymorphism Val380Leu might be interacting with environmental factors acting as a disease modifier.

Increased dopamine transporter density in Parkinson's disease patients with Social Anxiety Disorder.

Social Anxiety Disorder (SAD) is more common among PD patients than in the general population. This association may be explained by psychosocial mechanisms but it is also possible that neurobiological mechanism underlying PD can predispose to SAD. The aim of this study was to investigate a possible dopaminergic mechanism involved in PD patients with SAD, by correlating striatal dopamine transporter binding potential (DAT-BP) with intensity of social anxiety symptoms in PD patients using SPECT with TRODAT-1 as the radiopharmaceutical. Eleven PD patients with generalized SAD and 21 PD patients without SAD were included in this study; groups were matched for age, gender, disease duration and disease severity. SAD diagnosis was determined according to DSM IV criteria assessed with SCID-I and social anxiety symptom severity with the Brief Social Phobia Scale (BSPS). Demographic and clinical data were also collected. DAT-BP was significantly correlated to scores on BSPS for right putamen (r=0.37, p=0.04), left putamen (r=0.43, p=0.02) and left caudate (r=0.39, p=0.03). No significant correlation was found for the right caudate (r=0.23, p=0.21). This finding may reinforce the hypothesis that dopaminergic dysfunction might be implicated in the pathogenesis of social anxiety in PD.

PINK1 polymorphism IVS1-7 A-->G, exposure to environmental risk factors and anticipation of disease onset in Brazilian patients with early-onset Parkinson's Disease.

Parkinson's disease (PD) etiology has been attributed both to genetic and environmental factors, although the exact mechanisms of its pathogenesis remains elusive. We investigated Brazilian early-onset PD (EOPD) patients with PINK1 polymorphisms (SNPs) in order to find possible correlations between SNPs, environmental exposure, and disease age of onset. We enrolled 48 patients and 61 controls. PINK1 SNPs and environmental exposure (living in rural areas, well-water drinking, exposure to pesticides, herbicides and organic solvents and smoking) were investigated in both groups. We divided our group of patients into four subgroups, according to the presence/absence of PINK1 SNP IVS1-7 A-->G and the presence/absence of environmental factors exposure. We found a significant decrease (ANOVA test: p=0.02) of age at disease onset in those patients that had the IVS1-7 A-->G SNP and were exposed to environmental risk factors. Our data suggest that the interaction of PINK1 SNP IVS1-7 A-->G and environmental risk factors together have an important role in EOPD: each of them individually has a minor influence, whereas their interaction is associated with a significant effect in anticipating the disease clinical onset.

Konstantin N. Tretiakoff in Brazil: a historical perspective and discussion of his contribution to brazilian neuroscience.

The Hospício de Juquery, near the city of São Paulo (Brazil) was founded in 1896 and after few years it was decided that the institution should have the best possible facilities to study neuropathology. In 1921, a young psychiatrist, Antonio Carlos Pacheco e Silva was sent to the Hôpital de la Salpêtrière (Paris) to study neuropathology. There, Pacheco e Silva (later Prof.Pacheco e Silva) befriended Konstantin N. Tretiakoff accepted an invitation to become the first Chairman of the newly created neuropathology department of the Hospício de Juquery. During his stay in this institution, from 1922 to 1924 or early 1925, he worked very hard and produced many publications. Here we present and comment some of the papers he published in a Journal (Memórias do Hospício de Juquery - 'Memoirs de l'Hôspice de Juquery'), which had been recently created and present some information of this poorly known period of his life.

Clinical and molecular neuroimaging characteristics of Brazilian patients with Parkinson's disease and mutations in PARK2 or PARK8 genes.

OBJECTIVE: To describe clinical and neuroimaging (SPECT) characteristics of Brazilian patients with Parkinson's disease (PD) and mutations in PARK2 or PARK8 genes. METHOD: A total of 119 patients meeting clinical criteria for PD were evaluated. RESULTS: Of all patients studied, 13 had mutations in either PARK2 (n=9) or PARK8 genes (n=4). No statistically significant differences in clinical characteristics in both groups were seen. SPECT with [99mTc] TRODAT-1 showed significant differences between patient and control and the most remarkable difference was between PARK2 and control. CONCLUSION: The study found a frequency of mutation of 10.1% and it was most commonly seen in women. These patients had long disease course and high rates of dyskinesia after L-DOPA use. PARK8 patients did not have a relevant family history of PD.

Konstantin N. Tretiakoff in Brazil a historical perspective and discussion of his contribution to brazilian neuroscience / Konstantin N. Tretiakoff no Brasil: uma perspectiva histórica e discussão de sua contribuição à neurociência brasileira

The Hospício de Juquery, near the city of São Paulo (Brazil) was founded in 1896 and after few years it was decided that the institution should have the best possible facilities to study neuropathology. In 1921, a young psychiatrist, Antonio Carlos Pacheco e Silva was sent to the Hôpital de la Salpêtrière (Paris) to study neuropathology. There, Pacheco e Silva (later Prof.Pacheco e Silva) befriended Konstantin N. Tretiakoff accepted an invitation to become the first Chairman of the newly created neuropathology department of the Hospício de Juquery. During his stay in this institution, from 1922 to 1924 or early 1925, he worked very hardly and produced many publications. Here we present and comment some of the papers he published in a Journal (Memórias do Hospício de Juquery - "Memoirs de l'Hôspice de Juquery"), which had been recently created and present some information of this poorly known period of his life.

O Hospício de Juquery, perto da cidade de São Paulo (Brasil) foi fundado em 1896 e depois de poucos anos o Prof. Franco da Rocha, seu fundador, e os demais responsáveis pela instituição, com a ajuda do Governo do Estado de São Paulo, decidiram que deveriam criar as melhores instalações para o estudo da neuropatologia. Em 1921, o jovem psiquiatra Antonio Carlos Pacheco e Silva foi enviado para o Hôpital de la Salpêtrière (Paris) para estudar neuropatologia. Nessa instituição, Prof. Pacheco e Silva tornou-se amigo de um jovem neuropatologista, neurologista e psiquiatra russo Konstantin N. Tretiakoff que aceitou o desafio de chefiar o recém criado Departamento de Neuropatologia do Hospício de Juquery. Durante sua estada entre nós, de 1922 a 1924 ou início de 1925, ele trabalhou muito aplicadamente e produziu muitas publicações. Aqui nós apresentamos e comentamos alguns destes trabalhos que ele e seus associados publicaram em um novo Jornal (Memórias do Hospício de Juquery - "Memoirs de l'Hospice de Juquery") que circulou entre 1924 e 1927. Ademais, apresentamos algumas informações sobre esta parte menos conhecida de sua biografia.

Clinical and molecular neuroimaging characteristics of Brazilian patients with Parkinson's disease and mutations in PARK2 or PARK8 genes / Características clínicas e de neuroimagem molecular de pacientes brasileiros com doença de Parkinson e mutações nos genes PARK2 ou PARK8

OBJECTIVE: To describe clinical and neuroimaging (SPECT) characteristics of Brazilian patients with Parkinson's disease (PD) and mutations in PARK2 or PARK8 genes. METHOD: A total of 119 patients meeting clinical criteria for PD were evaluated. RESULTS: Of all patients studied, 13 had mutations in either PARK2 (n=9) or PARK8 genes (n=4). No statistically significant differences in clinical characteristics in both groups were seen. SPECT with [99mTc] TRODAT-1 showed significant differences between patient and control and the most remarkable difference was between PARK2 and control. CONCLUSION: The study found a frequency of mutation of 10.1 percent and it was most commonly seen in women. These patients had long disease course and high rates of dyskinesia after L-DOPA use. PARK8 patients did not have a relevant family history of PD.

OBJETIVO: Descrever as características clínicas e de neuroimagem (SPECT) de pacientes brasileiros com doença de Parkinson e mutações PARK2 e PARK8. MÉTODO: Foram avaliados 119 pacientes com critérios clínicos para a doença de Parkinson. RESULTADO: Entre os pacientes avaliados foram encontrados 13 pacientes com mutação nos genes PARK2 (n=9) ou PARK8 (n=4). Não houve diferença significativa na avaliação das características clínicas entre os dois grupos. Os resultados de SPECT mostraram diferenças significativas quanto ao potencial de ligação do [99mTc] TRODAT-1 SPECT entre pacientes vs. controle, sendo a diferença mais pronunciada entre PARK2 e controle. CONCLUSÃO: A freqüência de mutação encontrada foi 10,1 por cento, sendo mais comum em mulheres. Estes pacientes apresentavam longo tempo de doença e alta prevalência de discinesias associadas ao uso da levodopa. Nossos pacientes com PARK8 não apresentaram uma história familiar relevante de doença de Parkinson.

Botulinum toxin A for trismus in cephalic tetanus

O tétano cefálico é uma forma localizada de tétano. Da mesma maneira que nas formas generalizadas, o trismo é componente clínico, proeminente, leva a grande dificuldade na alimentaçäo, na deglutiçäo da saliva e para a higiene da boca. Essas dificuldades frequentemente precedem os problemas respiratórios e as pneumonias aspirativas, que se constituem em complicaçöes que ameaçam a vida dos pacientes. Drogas relaxantes musculares de outro tipo que as drogas curarizantes trazem pouco benefício para o trismo. A neurotoxina tetânica (tetanospasmin) e a toxina botulínica compartilham muitas semlhanças, como estrutura química símile, origem de microorganismos relacionados (clostridium tetani e Clostridium botulinum, respectivamente) e, presumivelmente, os mesmos mecanismos de açäo no neurônio. A diferença entre as duas reside na sua peculiar neuroespecificidade, atuando em diferentes neurônios. Injeçäo de doses reduzidas da toxina botulínica em músculos envolvidos em distonias focais ou outras desordens com espasticidade muscular localizada tem se mostrado eficaz em abolir as contraçöes. Descrevemos o uso da toxina botulínica A com sucesso no tratamento do trismo num paciente sofrendo de tétano cefálico. Acreditamos que esta forma de tratamento possa ser de valor no sentido de diminuir o risco de complicaçöes pulmonares nos pacientes com tétano

Discinesias induzidas por levodopa em 176 pacientes com doença de Parkinson / Levadopa induced dyskinesias in 176 patients with Parkinson's disease

A ocorrência de discinesias dificulta consideravelmente o manuseio terapêutico dos pacientes parkinsonianos tratados como levodopa. Estudamos asa caracrísticas clínicas das discinesias em 176 pacientes com diagnóstico de doença de Parkinson e tratados com levodopa. As discinesias ocorreram, em média, após 6,2 anos de duraçao da doença a após 4,2 anos de tratamento como levodopa. A maioris dos pacientes (90 por cento) achava-se nos estágios II e III de Hoehn & Yahr por ocasiao do início das discinesias. As discinesiasmais frequentes foram de "pico de dose" e "contínua". Movimento do tipo distônico ocorreu em 40 por cento dos casos e predominou nas discinesias de "fim de dose" e "bifásica". Distonia matinal correspondeu a 35 por cento dos casos de distonia. Movimentos coreiformes se manifestaram de forma gerenalizada em 43,2 por cento dos casos. Movimentos distônicos predominaram nos membros inferiores. A discinesia, qunado unilateral, ocorreu mais frequentemente no hemicorpo mais comprometido pela doença de Parkinson. A discinesia orofacial, quando isolada, foi mais frequentes nos pacientes mais idosos.

Experiência com aplicaçäo de toxina botulínica A em 115 pacientes / Botulinum toxin A: experience in the treatment of 115 patients

A toxina botulínica A é a forma mais eficaz de tratar algumas distonias focais e o espasmo hemifacial. Devido a seu custo ainda elevado no nosso país, seu uso ainda näo é disseminado. Mostramos nossa experiência com a toxina botulínica A em 115 pacientes, sendo 45 com espasmo hemifacial que apresentaram melhora acentuada ou total em 100 por cento. Em 20 pacientes com blefaroespasmo essencial houve melhora acentuada ou total em 70 por cento. Na síndrome de Meige, representada por 14 pacientes, a melhora acentuada ou total foi observada em 71,4 por cento. Em 23 pacientes com distonia cervical observou-se melhora acentuada em 65,2 por cento. Distonia da mäo, com 6 pacientes, apresentou o menor índdice de melhora acentuada (2 pacientes, 33,3 por cento). As complicaçöes de caráter transitório ocorreram, sendo as mais frequentes ptose palpebral e diminuiçäo da força palpebral e a mais grave, pneumonia aspirativa. Acreditamos que a toxina Ú forma eficaz e habitualmente segura de tratamento destas condiçöes clínicas.

Apomorfina: uma alternativa no controle das flutuaçöes motoras na doença de Parkinson / Apomorphine: an alternative in the control of motor fluctuations in Parkinson's disease

As flutuaçöes motoras (FM) decorrentes do uso prolongado de levedopa säo uma das principais complicaçöes do tratamento da doença de Parkinson (DP). A utilizaçäo da apomorfina, um potente agonista de receptores dopaminérgicos, associada ao domperidone para bloquear seus efeitos eméticos, surge como uma alternativa para contornar as FM dos parkinsonianos. Para adquirirmos experiência inicial com essa droga, decidimos estudar a açäo e os efeitos adversos da apomorfina em um grupo de quatro pacientes do nosso ambulatório com o diagnóstico de DP e com flutuaçöes do rendimento da levodopa. A apomorfina foi administrada por via subcutânea, sendo obtido o estado "on" em todos os pacientes com doses entre 1,5 e 3mg por aplicaçäo. A latência para o início do efeito variou de 7 a 30 minutos e a duraçäo da açäo de 60 a 85 minutos. O estado "on" produzido com a apomorfina foi indistinguível do observado com a levodopa, inclusive com a ocorrência de discinesias. Näo foram observados efeitos colaterais significativos. Nossa experiência inicial mostra que a apomorfina, em doses relativamente baixa, é uma alternativa eficaz para as FM da DP, com poucos efeitos colaterais

Acidentes vasculares cerebrais / Cerebrovascular diseases

Os acidentes vasculares cerebrais (AVC) continuam a ser causa importante de doenças neurológicas, com alta mortalidade envolvida na fase aguda e morbidade seqüelar importante a longo prazo. Nesta publicação os autores apresentam uma revisão do diagnóstico e do tratamento dos AVC isquêmicos, que se constituem na maioria dos casos. A abordagem inicial do paciente é crucial para a determinação do tipo de AVC, da extensão do comprometimento cerebral, das condições gerais do paciente e das comorbidades que possam estar presentes, permitindo delinear a melhor estratégia de tratamento. Avaliações do estado respiratório, cardiovascular, metabólico e do balanço hidroeletrolítico são fundamentais para melhor chance de sucesso. Um fator primordial é a determinação do tempo decorrido entre o início dos sintomas e a chegada do paciente ao hospital e sua avaliação neurológica e geral, para que se possa considerar a utilização de tratamento fibrinolítico, quando indicado. Pacientes com menos de três horas decorridas são os que, eventualmente, serão indicados para a trombólise endovenosa. Os critérios de indicação desta terapêutica, assim como do tratamento da hipertensão arterial nas fases iniciais são apresentados na forma de consensos consagrados. Da mesma maneira são apresentados e discutidos os protocolos de administração de fibrinolíticos e de anticoagulantes. Considerações sobre novos enfoques de tratamento neuroprotetor, ainda incipientes, são também apresentadas.(au)

Discinesia tardia: aspectos clínicos; fisiopatologia e tratamento / Tardive dyskinesia: clinical aspects;physiopathology and treatment

A discinesia tardia (DT), uma complicaçäo do uso da medicaçäo antipsicótica por longo período em pacientes psiquiátricos, apresenta inúmeros fatores de risco, que podem a influenciar na prevalência. Embora sua fisiopatologia näo esteja bem esclarecida foram demonstrados distúrbios na neurotransmissäo dopaminérgica no estriado envolvendo vários mecanismos e neurotransmissores. Apesar de todas as tentativas terapêuicas, até o momento näo se encontrou uma medicaçäo que pudesse reverter totalmente o quadro hoje exitente