Avaliação olfatória em pacientes com ataxia espinocerebelar tipo 10 em comparação a pacientes com ataxia espinocerebelar tipo 3, doença de Parkinson e controles

Orientador: Prof. Dr. Helio Afonso G. TeiveCo-orientadora: Profª. Drª. Laura S. MoriyamaTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Medicina Interna. Defesa : Curitiba, 13/12/2015Inclui referências : f. 58-72Resumo: As principais manifestações clínicas das ataxias espinocerebelares (AEC) resultam a partir do envolvimento do cerebelo e suas conexões aferentes e eferentes. O deficit olfativo tem sido descrito em diversas doenças neurodegenerativas, incluindo diferentes formas de ataxias autossômicas recessivas e dominantes. Porém, nenhum estudo até o momento mostrou se existe deficit olfativo em ataxia espinocerebelar tipo 10 (AEC10). Neste estudo, investigou-se de forma transversal a existência de deficit olfativo em pacientes com AEC10 comparando com ataxia espinocerebelar tipo 3 (AEC3), doença de Parkinson (DP) e controles saudáveis. Foram selecionados indivíduos que faziam acompanhamento no Ambulatório de Distúrbios do Movimento do Complexo Hospital de Clínicas da Universidade Federal do Paraná, incluindo 30 pacientes com AEC3, 30 com AEC10, 30 pacientes com doença de Parkinson (DP) e 100 controles saudáveis. Para avaliar a olfação destes pacientes foi utilizado o teste de identificação de cheiro Sniffin' Sticks (SS16). Foram coletados dados demográficos, exame neurológico e as escalas SARA e MEEM. Para a análise foram considerados apenas 44 indivíduos do grupo controle selecionados a partir do método de escore de propensão, que visou selecionar controles que tivessem a maior similaridade possível com os casos (AEC10 e AEC3). Do grupo com AEC10, 17 (56,7%) eram do sexo feminino, a média de idade era de 48,5 ± 11,4 anos e 14 (46,7%) eram tabagistas. Dos 30 pacientes com AEC3, 16 (53,3%) eram mulheres, a média de idade era 51,3 ± 9,8 anos e 10 (33,3%) eram tabagistas. O grupo de controles saudáveis foi composto por 30 (68,2%) mulheres e apresentou média de idade de 46,6 ± 11,1 anos e 21 (47,7%) eram tabagistas. O grupo com DP foi composto por 13 (43,3%) mulheres e apresentou média de idade de 66,4 ± 8,8 anos e apenas duas (6,7%) eram tabagistas. A média de duração da doença nos pacientes com AEC10 foi de 14,2 ± 11 anos e nos pacientes com AEC3 foi de 11,3 ± 6 anos. Os valores do escore de SS16 para o grupo AEC10 foi de 11,9 ± 2,9, no grupo AEC3 12,3 ± 1,9, no grupo da DP foi de 6,6 ± 2,8 e no grupo controle de 12,1 ± 2,0. Quando realizada a comparação do escore do SS16 entre os grupos a AEC10 não apresentou um deficit olfativo significativo quando comparado ao grupo de AEC3 ou controles, porém apresentou um resultado significativo quando comparado ao grupo de DP (p < 0,001). O número de expansões também foi analisado em 17 pacientes com AEC10 e em 14 pacientes com AEC3 e esta associação entre o número de repetições do gene com o escore do teste de SS16, não foi estatisticamente significativa (p = 0,739 e p = 0,303, respectivamente). Quando realizada a associação entre o escore de SS16 e duração da doença, esta também não encontrou significância estatística. Porém, quando se estudou a associação entre o escore de SS16 e escore de Mini Mental, esta foi estatisticamente significativa no grupo controle (p = 0,007), no grupo AEC3 (p = 0,005) e no grupo AEC10 (p = 0,001). Este estudo confirma descobertas anteriores de hiposmia em ataxia quando comparado à doença de Parkinson, porém não foi encontrada nenhuma associação deste deficit olfatório com a duração da doença ou com número de repetição no gene, mas sim com o escore do MEEM. Palavras-chave: Ataxia; Cerebelo; Cognição; Olfato.Abstract: The main clinical manifestations of spinocerebellar ataxias (SCA) result from the involvement of the cerebellum and its afferent and efferent connections. Previous studies have shown olfactory deficits in different forms of ataxia as SCA2, Friedreich ataxia and in small groups of diverse aetiology ataxia. However, no one showed olfactory deficit in spinocerebellar ataxia type 10 (SCA10). This was a cross-sectional study investigating the existence of olfactory deficit in patients with SCA10 compared to SCA3, patients with Parkinson's disease (PD) and healthy controls. Individuals were recruited from the movement disorders clinic of the Federal University of Paraná. Including 30 patients with SCA3, 30 with SCA10, 30 with PD and 100 healthy controls. The authors used a 16-item smell identification test from Sniffin' Sticks (SS16) to assess the olfaction of these patients. Were collected demographic data of the patients, all of them underwent a neurological examination and were applied the SARA scale and the MMSE. For the analysis were considered only 44 individuals in the control group selected from the Propensity score method, which aimed to select controls that had the greatest similarity with possible cases (10 AEC and AEC3). From the SCA10 group 17 (56.7%) were female, the mean age was 48.5 ± 11.4 years and a total of 14 (46.7%) were smokers. Of the 30 patients with SCA3, 16 (53.3%) were women; the mean age was 51.3 ± 9.8 years and 10 (33.3%) were smokers. The group of healthy controls, 30 (68.2%) were women, mean age was 46.6 ± 11.1 years and 21 47.7%) were smokers. The PD group, were composed of 13 (43.3%) women, the mean age was 66.4 ± 8.8 years and only 2 (6.7%) were smokers. The mean disease duration of SCA10 patients was 14.2 ± 11 years and in patients with SCA3 was 11.3 ± 6. The mean SS16 score for the SCA10 group was 11.9 ± 2.9, and 12.3 ± 1.9 in the SCA3, the PD group mean SS16 score was 6.6 ± 2.8 and control group 12.1 ± 2.0. The SS16 score did not preset a significant olfactory deficits when compared to SCA10 with SCA3 or control group, however was a significant higher in ataxias than in DP group (p < 0.001). The number of repeat expansions was also analyzed in 17 SCA10 patients and 14 SCA3 patients. When analyzed the association between the number of repeat expansion and the SS16 score, this was not statistically significant p = 0.739 and p = 0.303 respectively. When performed the evaluation of the association between the SS16 score and the disease duration this also not found statistical significance. However the association between the score of SS16 and Mini Mental score was statistically significant in the control group (p = 0.007), SCA3 group (p = 0.005) and SCA10 group (p = 0.001).This study confirms previous findings in ataxia hyposmia when compared with Parkinson's disease. However association of the olfactory deficit with disease duration or repeat expansion was not found. Keywords: Ataxia; Cerebellum; Cognition; Smell

Shell Shock: Psychogenic Gait and Other Movement Disorders—A Film Review

Background: The psychological pressure on soldiers during World War I (WWI) and other military conflicts has resulted in many reported cases of psychogenic gait as well as other movement disorders. In this paper, psychogenic movement disorders captured in the WWI film footage “War Neuroses” is reanalyzed. Methods: Two movement disorders specialists re-examined film images of 21 WWI patients with various and presumed psychogenic manifestations, pre- and post treatment. The film was recorded by Arthur Hurst, a general physician with an interest in neurology. Results: All 21 subjects were males, and all presented with symptoms relating to war trauma or a psychological stressor (e.g., being buried, shrapnel wounds, concussion, or trench fever). The most common presenting feature was a gait disorder, either pure or mixed with another movement disorder (15), followed by retrograde amnesia (2), abnormal postures (pure dystonia) (1), facial spasm (1), head tremor (1), “hyperthyroidism-hyperadrenalism” (1). Nineteen patients received treatment, and the treatment was identified in nine cases. In most cases, treatment was short and patients improved almost immediately. Occupational therapy was the most common treatment. Other effective methods were hypnosis (1), relaxation (1), passive movements (2), and probable “persuasion and re-education” (6). Discussion: The high success rate in treating psychogenic disorders in Hurst's film would be considered impressive by modern standards, and has raised doubt in recent years as to whether parts of the film were staged and/or acted

Allogeneic stem cell transplantation as a curative option in relapse/refractory diffuse large B cell lymphoma: Spanish multicenter GETH/GELTAMO study

Grupo Español de Trasplante Hematopoyético (GETH) and Grupo Español de Linfoma y Trasplante Autólogo (GELTAMO).We performed a retrospective multicenter study including 140 patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) who underwent allogeneic hematopoietic stem cell transplantation (allo-SCT) from March 1995 to November 2018. Our objective was to analyze long term outcomes. Seventy-four percent had received a previous auto-SCT (ASCT) and the median number of lines pre-allo-SCT was 3 (range 1–9). Three year-event free survival (EFS) and overall survival (OS) were 38% and 44%, respectively. Non-relapse mortality (NRM) at day 100 was 19%. Cumulative incidence of grade III–IV acute graft versus host disease (GVHD) at day 100 was 16% and moderate/severe chronic GVHD at 3 years 34%. Active disease at allo-SCT (HR 1.95, p = 0.039) (HR 2.19, p = 0.019), HCT-CI ≥ 2 (2.45, p = 0.002) (HR 2.33, p = 0.006) and donor age >37 years (HR 2.75, p = 0.014) (HR 1.98, p = 0.043) were the only independent variables both for PFS and OS, respectively. NRM was significantly modified by HCT-CI ≥ 2 (HR 4.8, p = 0.008), previous ASCT (HR 4.4, p = 0.048) and grade III–IV acute GVHD on day 100 (HR 6.13, p = 0.016). Our data confirmed that allo-SCT is a curative option for patients with R/R DLBCL, displaying adequate results for fit patients with chemosensitive disease receiving an allo-SCT from a young donor

Cholinergic Pathway SNPs and Postural Control in 477 Older Adults

Objective: To determine whether single nucleotide polymorphisms (SNPs) of the cholinergic system and quantitative parameters of postural control are associated in healthy older adults. This is a cross-sectional analysis from the TREND study.Methods: All participants performed a static postural control task for 30 s on a foam pad in semitandem stance and eyes closed. We analyzed mean power frequency (MPF), area, acceleration, jerk, and velocity from a mobile sensor worn at the lower back using a validated algorithm. Genotypes of four SNPs in genes involved in the cholinergic system (SLC5A7, CHAT, BCHE, CHRNA4) were extracted from the NeuroX chip. All participants present a normal neurological examination and a Minimental state examination score &gt;24.Results: Four hundred and seventy seven participants were included. Mean age was 69 years, 41% were female. One SNP of the cholinergic pathway was significantly associated with a quantitative postural control parameter. The minor allele of rs6542746 in SLC5A7 was associated with lower MPF (4.04 vs. 4.22 Hz; p = 3.91 × 10-4). Moreover, the following associations showed trends toward significance: minor allele of rs6542746 in SLC5A7 with higher anteroposterior acceleration (318 vs. 287 mG; p = 0.005), and minor allele of rs3810950 in CHAT with higher mediolateral acceleration [1.77 vs. 1.65 log(mG); p = 0.03] and velocity [1.83 vs. 1.74 log(mm/s); p = 0.019]. Intraindividual occurrence of rs6542746 and rs3810950 minor alleles was dose-dependently related with lower MPF (p = 0.004).Conclusion: This observational study suggests an influence of SNPs of the cholinergic pathway on postural control in older adults

Motor, cognitive and mobility deficits in 1000 geriatric patients : protocol of a quantitative observational study before and after routine clinical geriatric treatment – the ComOn-study

© The Author(s). 2020 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany). Methods: This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week's inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters. Discussion: This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.info:eu-repo/semantics/publishedVersio

Shell Shock: Psychogenic Gait and Other Movement Disorders - A Film Review

Background: The psychological pressure on soldiers during World War I (WWI) and other military conflicts has resulted in many reported cases of psychogenic gait as well as other movement disorders. In this paper, psychogenic movement disorders captured in the WWI film footage "War Neuroses" is reanalyzed. Methods: Two movement disorders specialists re-examined film images of 21 WWI patients with various and presumed psychogenic manifestations, pre- and post treatment. The film was recorded by Arthur Hurst, a general physician with an interest in neurology. Results: All 21 subjects were males, and all presented with symptoms relating to war trauma or a psychological stressor (e.g., being buried, shrapnel wounds, concussion, or trench fever). The most common presenting feature was a gait disorder, either pure or mixed with another movement disorder (15), followed by retrograde amnesia (2), abnormal postures (pure dystonia) (1), facial spasm (1), head tremor (1), "hyperthyroidism-hyperadrenalism" (1). Nineteen patients received treatment, and the treatment was identified in nine cases. In most cases, treatment was short and patients improved almost immediately. Occupational therapy was the most common treatment. Other effective methods were hypnosis (1), relaxation (1), passive movements (2), and probable "persuasion and re-education" (6). Discussion: The high success rate in treating psychogenic disorders in Hurst's film would be considered impressive by modern standards, and has raised doubt in recent years as to whether parts of the film were staged and/or acted.</p

Increased sexual arousal in patients with movement disorders

ABSTRACT Increased of sexual arousal (ISA) has been described in different neurological diseases. The purpose of this study was present a case series of ISA in patients with movement disorders. Method Fifteen patients with different forms of movement disorders (Parkinson’s disease, Huntington’s disease, Tourette´s syndrome, spinocerebellar ataxia type 3), were evaluated in the Movement Disorders Unit of the Federal University of Paraná. Results Among Parkinson’s disease patients there were seven cases with different forms of ISA due to dopaminergic agonist use, levodopa abuse, and deep brain stimulation (DBS). In the group with hyperkinetic disorders, two patients with Huntington’s disease, two with Tourette’s syndrome, and four with spinocerebellar ataxia type 3 presented with ISA. Conclusions ISA in this group of patients had different etiologies, predominantly related to dopaminergic treatment or DBS in Parkinson’s disease, part of the background clinical picture in Huntington’s disease and Tourette’s syndrome, and probably associated with cultural aspects in patients with spinocerebellar ataxia type 3

Spinocerebellar ataxia type 3: subphenotypes in a cohort of brazilian patients

Spinocerebellar ataxia type 3 (SCA3) involves cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems with strong phenotypic heterogeneity, that lead us to classify the disorder into different clinical subtypes according to the predominantly affected motor systems. Method The series comprises 167 SCA3 patients belonging to 68 pedigrees, studied from 1989-2013. These patients were categorized into seven different subphenotypes. Results SCA3 cases were clustered according to the predominant clinical features. Three most common forms were subphenotype 2, characterized by ataxia and pyramidal symptom was observed in 67.5%, subphenotype 3 with ataxia and peripheral signs in 13.3%, and subphenotype 6 with pure cerebellar syndrome in 7.2%. Conclusion Our study was the first to systematically classify SCA3 into seven subphenotypes. This classification may be particularly useful for determination of a more specific and direct phenotype/genotype correlation in future studies