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People recovered from COVID-19 may still present complications including respiratory and neurological sequelae. In other viral infections, cognitive impairment occurs due to brain damage or dysfunction caused by vascular lesions and inflammatory processes. Persistent cognitive impairment compromises daily activities and psychosocial adaptation. Some level of neurological and psychiatric consequences were expected and described in severe cases of COVID-19. However, it is debatable whether neuropsychiatric complications are related to COVID-19 or to unfoldings from a severe infection. Nevertheless, the majority of cases recorded worldwide were mild to moderate self-limited illness in non-hospitalized people. Thus, it is important to understand what are the implications of mild COVID-19, which is the largest and understudied pool of COVID-19 cases. We aimed to investigate adults at least four months after recovering from mild COVID-19, which were assessed by neuropsychological, ocular and neurological tests, immune markers assay, and by structural MRI and 18FDG-PET neuroimaging to shed light on putative brain changes and clinical correlations. In approximately one-quarter of mild-COVID-19 individuals, we detected a specific visuoconstructive deficit, which was associated with changes in molecular and structural brain imaging, and correlated with upregulation of peripheral immune markers. Our findings provide evidence of neuroinflammatory burden causing cognitive deficit, in an already large and growing fraction of the world population. While living with a multitude of mild COVID-19 cases, action is required for a more comprehensive assessment and follow-up of the cognitive impairment, allowing to better understand symptom persistence and the necessity of rehabilitation of the affected individuals.
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COVID-19 , Disfunção Cognitiva , Adulto , Humanos , COVID-19/complicações , Neuroimagem , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Dystonia is associated with disabling nonmotor symptoms like chronic pain (CP), which is prevalent in dystonia and significantly impacts the quality of life (QoL). There is no validated tool for assessing CP in dystonia, which substantially hampers pain management. OBJECTIVE: The aim was to develop a CP classification and scoring system for dystonia. METHODS: A multidisciplinary group was established to develop the Dystonia-Pain Classification System (Dystonia-PCS). The classification of CP as related or unrelated to dystonia was followed by the assessment of pain severity score, encompassing pain intensity, frequency, and impact on daily living. Then, consecutive patients with inherited/idiopathic dystonia of different spatial distribution were recruited in a cross-sectional multicenter validation study. Dystonia-PCS was compared to validated pain, mood, QoL, and dystonia scales (Brief Pain Inventory, Douleur Neuropathique-4 questionnaire, European QoL-5 Dimensions-3 Level Version, and Burke-Fahn-Marsden Dystonia Rating Scale). RESULTS: CP was present in 81 of 123 recruited patients, being directly related to dystonia in 82.7%, aggravated by dystonia in 8.8%, and nonrelated to dystonia in 7.5%. Dystonia-PCS had excellent intra-rater (Intraclass Correlation Coefficient - ICC: 0.941) and inter-rater (ICC: 0.867) reliability. In addition, pain severity score correlated with European QoL-5 Dimensions-3 Level Version's pain subscore (r = 0.635, P < 0.001) and the Brief Pain Inventory's severity and interference scores (r = 0.553, P < 0.001 and r = 0.609, P < 0.001, respectively). CONCLUSIONS: Dystonia-PCS is a reliable tool to categorize and quantify CP impact in dystonia and will help improve clinical trial design and management of CP in patients affected by this disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Distonia , Distúrbios Distônicos , Transtornos dos Movimentos , Humanos , Distonia/diagnóstico , Distonia/complicações , Qualidade de Vida , Estudos Transversais , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Distúrbios Distônicos/complicações , Distúrbios Distônicos/diagnóstico , Transtornos dos Movimentos/complicações , DorRESUMO
INTRODUCTION/AIMS: Amyotrophic lateral sclerosis (ALS) type 8 (ALS8) is caused by VAPB gene mutations. The differences between neuropsychological and behavioral profiles of patients with sporadic ALS (sALS) and those with ALS8 are unclear. We aimed to compare cognitive performance and behavioral aspects between sALS and ALS8 patients. METHODS: Our study included 29 symptomatic ALS8 patients (17 men; median age 49 years), 20 sALS patients (12 men; median age 55 years), and 30 healthy controls (16 men; median age 50 years), matched for sex, age, and education. Participants underwent neuropsychological assessments focused on executive functions, visual memory, and facial emotion recognition. Behavioral and psychiatric symptoms were evaluated using the Hospital Anxiety and Depression Scale and the Cambridge Behavioral Inventory. RESULTS: Clinical groups (sALS and ALS8) exhibited lower global cognitive efficiency and impaired cognitive flexibility, processing speed, and inhibitory control compared with controls. ALS8 and sALS showed similar performance in most executive tests, except for poorer verbal (lexical) fluency in those with sALS. Apathy, anxiety, and stereotypical behaviors were frequent in both clinical groups. DISCUSSION: sALS and ALS8 patients demonstrated similar deficits in most cognitive domains and had comparable behavioral profiles. These findings should be considered in the care of patients.
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Esclerose Lateral Amiotrófica , Apatia , Masculino , Humanos , Pessoa de Meia-Idade , Esclerose Lateral Amiotrófica/diagnóstico , Função Executiva , Cognição , Testes NeuropsicológicosRESUMO
BACKGROUND: Episodic memory impairment may occur in progressive supranuclear palsy (PSP). However, it remains uncertain whether this is due to executive dysfunction or to the involvement of brain areas responsible for memory. OBJECTIVES: To investigate the specific brain regions underlying episodic memory impairment in PSP. METHODS: Twenty-one patients with PSP and 20 healthy controls underwent the Figure Memory Test (FMT) from the Brief Cognitive Screening Battery and brain MRI. We explored correlations between gray matter volumes and memory scores in PSP patients, adjusting for age and performance on the Frontal Assessment Battery. RESULTS: PSP patients performed worse than controls (p < 0.001) on delayed recall in the FMT. Delayed recall scores correlated to bilateral hippocampal and parahippocampal volumes in PSP patients. CONCLUSIONS: Medial temporal structures may play a role in episodic memory impairment in PSP, suggesting that amnesia in PSP is not solely due to executive dysfunction.
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Memória Episódica , Paralisia Supranuclear Progressiva , Encéfalo/diagnóstico por imagem , Humanos , Transtornos da Memória/diagnóstico por imagem , Transtornos da Memória/etiologia , Neuroimagem , Testes Neuropsicológicos , Paralisia Supranuclear Progressiva/complicações , Paralisia Supranuclear Progressiva/diagnóstico por imagemAssuntos
Ataxia Cerebelar/fisiopatologia , Polineuropatias/fisiopatologia , Síndrome de Sjogren/fisiopatologia , Distúrbios Somatossensoriais/fisiopatologia , Adulto , Idoso , Ataxia/diagnóstico por imagem , Ataxia/etiologia , Ataxia/fisiopatologia , Atrofia , Ataxia Cerebelar/diagnóstico por imagem , Ataxia Cerebelar/etiologia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Eletrodiagnóstico , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa , Polineuropatias/etiologia , Síndrome de Sjogren/complicações , Distúrbios Somatossensoriais/etiologiaAssuntos
Blefarospasmo/tratamento farmacológico , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/uso terapêutico , Espasmo Hemifacial/tratamento farmacológico , Injeções/métodos , Fármacos Neuromusculares/administração & dosagem , Fármacos Neuromusculares/uso terapêutico , Adulto , Idoso , Toxinas Botulínicas Tipo A/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fármacos Neuromusculares/efeitos adversos , Órbita , Articulações Tarsianas , Resultado do TratamentoRESUMO
Background: Handicap is a patient-centered measure of health status that encompasses the impact of social and physical environment on daily living, having been assessed in advanced and late-stage Parkinson's Disease (PD). Objective: To characterize the handicap of a broader sample of patients. Methods: A cross-sectional study of 405 PD patients during the MDS-UPDRS Portuguese validation study, using the MDS-UPDRS, Unified Dyskinesias Rating Scale, Nonmotor symptoms questionnaire, PDQ-8 and EQ-5D-3L. Handicap was measured using the London Handicap Scale (LHS). Results: Mean age was 64.42 (±10.3) years, mean disease duration 11.30 (±6.5) years and median HY 2 (IQR, 2-3). Mean LHS was 0.652 (±0.204); "Mobility," "Occupation" and "Physical Independence" were the most affected domains. LHS was significantly worse in patients with longer disease duration, older age and increased disability. In contrast, PDQ-8 did not differentiate age groups. Handicap was significantly correlated with disease duration (r = -0.35), nonmotor experiences of daily living (EDL) (MDS-UPDRS-I) (r = -0.51), motor EDL (MDS-UPDRS-II) (r = -0.69), motor disability (MDS-UPDRS-III) (r = -0.49), axial signs of MDS-UPDRS-III (r = -0.55), HY (r = -0.44), presence of nonmotor symptoms (r = -0.51) and PDQ-8 index (r = -0.64) (all P < 0.05). Motor EDL, MDS-UPDRS-III and PDQ-8 independently predicted Handicap (adjusted R 2 = 0.582; P = 0.007). Conclusions: The LHS was easily completed by patients and caregivers. Patients were mild-moderately handicapped, which was strongly determined by motor disability and its impact on EDL, and poor QoL. Despite correlated, handicap and QoL seem to differ in what they measure, and handicap may have an added value to QoL. Handicap seems to be a good measure of perceived-health status in a broad sample of PD.
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INTRODUCTION: The VAPB gene is associated with fALS (fALS 8). This disease presents a variable phenotype and no study sought to characterize its neuroanatomical abnormalities until now. This study aims to evaluate structural brain and spinal cord abnormalities in symptomatic and pre-symptomatic VAPB-related ALS. METHODS: This cohort included 10 presymptomatic and 20 symptomatic carriers of the Pro56Ser VAPB variant as well as 30 matched controls and 20 individuals with sporadic ALS. They underwent detailed clinical evaluation and MRI in a 3 T scanner. Using volumetric T1 sequence, we computed cerebral cortical thickness (FreeSurfer), basal ganglia volumetry (T1 Multi-atlas) and SC morphometry (SpineSeg). DTI was used to assess white matter integrity (DTI Multi-atlas). Groups were compared using a generalized linear model with Bonferroni-corrected p values<0.05. We also plotted VAPB brain expression map using Allen Human Brain Atlas to compare with imaging findings. RESULTS: Mean age of presymptomatic and symptomatic subjects were 43.2 and 51.9 years, respectively. Most patients had a predominant lower motor neuron phenotype (16/20). Sleep complaints and tremor were the most frequent additional manifestations. Compared to controls, symptomatic subjects had pallidal, brainstem and SC atrophy, whereas presymptomatic only had SC atrophy. This pattern also contrasted with the sALS group that presented motor cortex and corticospinal abnormalities. Brain structural damage and VAPB expression maps were highly overlapping. CONCLUSION: VAPB-related ALS has a distinctive structural signature that targets the basal ganglia, brainstem and SC, which are regions with high VAPB expression. Neuroanatomical SC changes are evident before clinical onset of the disease.
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Esclerose Lateral Amiotrófica , Substância Branca , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Esclerose Lateral Amiotrófica/genética , Atrofia , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Medula Espinal/diagnóstico por imagem , Proteínas de Transporte Vesicular , Substância Branca/diagnóstico por imagemRESUMO
Background: Progressive supranuclear palsy (PSP) is the most common atypical parkinsonism and has executive dysfunction as a core feature. The magnitude of episodic memory disturbance in PSP is yet to be clarified. Objectives: To investigate how impaired is episodic memory in PSP compared to healthy controls and other neuropsychiatric disorders. Also, we sought to identify the brain correlates underlying these memory disturbances. Methods: We performed a systematic search on PubMed and Scopus, combining the terms "progressive supranuclear palsy" AND "memory". The search was limited to papers published in English, French, Portuguese or Spanish, with no chronological filters. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Results: The initial search returned 464 results. After extraction of duplicates, 356 records were screened, leading to inclusion of 38 studies. Most studies found that PSP patients had lower scores on episodic memory compared to healthy controls. In addition, the majority of studies suggest that PSP does not differ from Parkinson's disease and from atypical parkinsonism in terms of episodic memory performance. The same is seen for PSP and frontotemporal dementia. Conversely, episodic memory impairment seems to be greater in typical Alzheimer's disease compared to PSP. Neuroimaging findings indicate that striatofrontal structures may be involved in PSP episodic memory dysfunction, while no associations with mesial structures (including hippocampi) were found. Conclusions: Episodic memory is impaired in PSP. Whether this amnesia refers to executive dysfunction is still controversial. More studies are warranted to clarify the neural basis of memory impairment in PSP.
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Mentalizing and emotion recognition are impaired in behavioral variant frontotemporal dementia (bvFTD). It is not clear whether these abilities are also disturbed in other conditions with prominent frontal lobe involvement, such as progressive supranuclear palsy (PSP). Our aim was to investigate social cognition (facial emotion recognition, recognition of social norms violation and mentalizing) in bvFTD and PSP. The neural basis of these functions in PSP and bvFTD groups, by analysis of structural neuroimaging, were also investigated. Twenty-three bvFTD patients, 21 PSP patients and 23 healthy controls were included. All participants underwent 3T brain MRI and a full cognitive exam including the short version of Social and Emotional Assessment (Mini-SEA), which is composed of a facial emotion recognition test (FERT) and the faux pas test. Two components of the faux pas test were distinguished: a score assessing the recognition of social norms violation and a score assessing mentalizing. Compared to controls, bvFTD and PSP patients had significantly reduced scores in all tests of social cognition but did not differ on these measures. PSP and bvFTD had cerebral atrophy in critical regions for social cognition processes, when compared to controls. The cortical correlates of emotion recognition partially overlapped in bvFTD and PSP, with correlations retrieved within the frontal medial cortex, cingulate, insula and limbic structures. PSP and bvFTD patients also displayed similar patterns of brain correlations for the composite score of social norms, with a significant cluster in anterior temporal lobes. Mentalizing scores were associated with frontal and temporal poles bilaterally, in both bvFTD and PSP. These findings support previous observations that PSP patients exhibit impairment in complex cognitive abilities, such as mentalizing. Moreover, these data extend previous findings showing that PSP and bvFTD share key clinical, cognitive and neuroimaging features.
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Demência Frontotemporal , Mentalização , Doença de Pick , Paralisia Supranuclear Progressiva , Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/psicologia , Humanos , Testes Neuropsicológicos , Paralisia Supranuclear Progressiva/diagnóstico por imagem , Paralisia Supranuclear Progressiva/psicologiaRESUMO
Hereditary sensory neuropathies (HSN) are a group of rare neurological disorders with heterogeneous clinical and genetic characteristics. Although at least 17 different genes have already been associated with HSN, the epidemiology of the disorder in Brazil is still unknown. Performing whole genome sequencing (WGS) in 23 unrelated Brazilian families diagnosed with HSN, we detected pathogenic variants in ATL3, SPTLC2, and SCN9A in 12 patients belonging to five unrelated families. Clinical features associated with heterozygous mutations in ATL3 (c.575A > G; p.(Tyr192Cys)) and SPTLC2 (c.529A > G; p.(Asn177Asp)) were sensory deficits, neuropathic pain, and recurrent ulcerations. Presenting as congenital insensitivity to pain, three unrelated probands carried biallelic loss-of-function mutations in SCN9A. The so far undescribed stop mutation c.2106G > A (p.(Trp702Ter)) and the likewise novel splicing variant c.3319-1G > A were found in compound-heterozygosity with, respectively, the known pathogenic variants c.2908G > T (p.Trp970Ter) and c.2690G > A (p.Glu897Ter). In total, we identified pathogenic mutations in 21.7% of our families, which suggests that most of the cases could be explained by yet to be discovered genes or unusual alleles. Our study represents the first mutational screen in a Brazilian HSN cohort, enabling additional insights for genotype-phenotype correlations, reducing misdiagnoses, and providing early treatment considerations.
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Neuropatias Hereditárias Sensoriais e Autônomas , Insensibilidade Congênita à Dor , Brasil , GTP Fosfo-Hidrolases/genética , Neuropatias Hereditárias Sensoriais e Autônomas/genética , Heterozigoto , Humanos , Mutação/genética , Canal de Sódio Disparado por Voltagem NAV1.7/genética , Insensibilidade Congênita à Dor/genética , Serina C-PalmitoiltransferaseRESUMO
The aim of the study was to evaluate the frequency and to perform phenotypic and genotypic characterization of familial Parkinsonism and early onset Parkinson's disease (EOPD) in a Brazilian movement disorder unit. We performed a standardized clinical assessment of patients followed by sequencing of PRKN, PINK1 in EOPD cases and SNCA, LRRK2 in familial Parkinsonism individuals. During the period of study (January through December, 2006), we examined 575 consecutive patients of whom 226 (39.3%) met the diagnosis of Parkinsonism and idiopathic Parkinson's disease (IPD) was diagnosed in 202 of the latter. Of the IPD cases, 45 (22.3%) had EOPD. The age at onset in the EOPD cases (n = 45) was 34.8 +/- 5.4 years (mean +/- standard deviation). The age at onset in the familial late-onset PD patients (n = 8) was 52.3 +/- 12.2 years. In the early onset cases, we identified five known mutations in PRKN, two single heterozygous and three compound heterozygous (P153R, T240M, 255Adel, W54R, V3I); in addition, we identified one novel mutation in PINK1 (homozygous deletion of exon 7). In the familial cases (late onset), 1 patient had a novel LRRK2 variant, Q923H, but no SNCA mutations were identified. We have demonstrated that EOPD accounts for a high frequency of IPD cases in our tertiary referral center. PRKN was the most commonly mutated gene, but we also identified a novel mutation in PINK1 and a novel variant in LRRK2.
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Predisposição Genética para Doença , Mutação/genética , Doença de Parkinson/genética , Transtornos Parkinsonianos/genética , Fenótipo , Proteínas Quinases/genética , Proteínas Serina-Treonina Quinases/genética , Ubiquitina-Proteína Ligases/genética , alfa-Sinucleína/genética , Adulto , Idade de Início , Idoso , Aminoácidos/genética , Brasil/epidemiologia , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Dados de Sequência MolecularRESUMO
OBJECTIVE: Amyotrophic lateral sclerosis type 8 (ALS8) is a familial form of motor neuron disease, with predominance of lower motor neuron degeneration, and is caused by mutation of the vesicle-associated membrane protein-associated protein B (VAPB). We aimed to compare the cognitive profile of patients with ALS8 and healthy controls (HC), and to screen for behavioural features in ALS8 patients. METHODS: The sample was composed of ALS8 patients (n = 22; 14 men; median age 48 years old; median disease duration 6.5 years) and HC (n = 33; 19 men; median age 48 years old). Patients and HC were matched for sex, age and educational level. Participants underwent behavioural, psychiatric (Hospital Anxiety and Depression Scale and Cambridge Behavioural Inventory-Revised) and neuropsychological assessments, focused on executive functions, visual memory, and facial emotion recognition. RESULTS: ALS8 patients exhibited subtle deficits in executive functions. Compared to controls, ALS8 patients were significantly impaired in measures of flexibility and inhibitory control. ALS8 patients and HC did not differ in scores of facial emotion recognition. There was clinically relevant anxiety and depression in 36% and 27% of ALS8 patients, respectively. Behavioural disorders such as stereotypic and motor behaviours were present in more than 30% of patients. CONCLUSIONS: ALS8 patients present mild executive dysfunction and behavioural changes such as mood disorders, apathy and stereotypic behaviour. Our findings suggest that ALS8 is not a pure motor disorder and it is associated with subtle cognitive and behavioural impairments.
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Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/psicologia , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Transtornos Motores/epidemiologia , Transtornos Motores/psicologia , Adulto , Esclerose Lateral Amiotrófica/diagnóstico , Estudos Transversais , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Pessoa de Meia-Idade , Transtornos Motores/diagnóstico , Testes NeuropsicológicosRESUMO
Dopa responsive Dystonia (DRD) was first described in 1971 and typically begins at childhood with gait dysfunction caused by foot dystonia progressing to affect other extremities. There is marked diurnal fluctuation and sustained improvement of symptoms with low dose levodopa therapy. Heterozygous mutation of the gene GCH1 has been shown to cause DRD. We studied GCH1 in nine patients with DRD from six families of Federal University of Minas Gerais Movement Disorders Clinic. We identified three mutations; two affected siblings carried a novel T209P mutation and two siblings from another family were compound heterozygous carriers of Met211Val and Lys224Arg mutations. To our knowledge this is the first report of GCH1 mutations underlying DRD in patients from Brazil.
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Dopaminérgicos/uso terapêutico , Distonia/tratamento farmacológico , Distonia/genética , GTP Cicloidrolase/genética , Levodopa/uso terapêutico , Mutação/genética , Arginina/genética , Brasil/epidemiologia , Saúde da Família , Humanos , Lisina/genética , Metionina/genética , Valina/genéticaAssuntos
Arginina/genética , Cisteína/genética , DNA Polimerase Dirigida por DNA/genética , Mutação/genética , Oftalmoplegia Externa Progressiva Crônica/genética , Adulto , Brasil , Cardiomiopatias/complicações , Cardiomiopatias/genética , Análise Mutacional de DNA , DNA Polimerase gama , Depressão/complicações , Depressão/genética , Eletromiografia , Feminino , Transtornos Neurológicos da Marcha/complicações , Transtornos Neurológicos da Marcha/genética , Humanos , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Condução Nervosa , Oftalmoplegia Externa Progressiva Crônica/complicações , Oftalmoplegia Externa Progressiva Crônica/patologia , Doença de Parkinson/complicações , Doença de Parkinson/genética , Fenótipo , Succinato Desidrogenase/metabolismoRESUMO
We report the first Brazilian family with Brown-Vialetto-van Laere syndrome. The presence of consanguineous marriages and illness affecting three sisters and one niece support an autosomal recessive transmission. The age at onset of the illness ranged from 12 to 20 years old. The time interval between hearing loss and involvement of other cranial nerves varied from 3 to 12 years. MRI demonstrated bulbar atrophy and also high intensity signal at T2 weighted and fluid attenuated inversion recovery (FLAIR) sequences.
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Paralisia Bulbar Progressiva/genética , Perda Auditiva Neurossensorial/genética , Padrões de Herança/genética , Adolescente , Atrofia , Paralisia Bulbar Progressiva/diagnóstico , Feminino , Perda Auditiva Neurossensorial/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Linhagem , SíndromeRESUMO
The definition and classification of the dystonias was recently revisited. In the new 2013 classification, the dystonias are subdivided in terms of their etiology according to whether they are the result of pathological changes or structural damage, have acquired causes or are inherited. As hereditary dystonias are clinically and genetically heterogeneous, we sought to classify them according to the new recently defined criteria. We observed that although the new classification is still the subject of much debate and controversy, it is easy to use in a logical and objective manner with the inherited dystonias. With the discovery of new genes, however, it remains to be seen whether the new classification will continue to be effective.
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Distonia/classificação , Distonia/genética , Distúrbios Distônicos/classificação , Distúrbios Distônicos/genética , Adolescente , Adulto , Idade de Início , Criança , Coreia/classificação , Coreia/genética , Feminino , Humanos , Masculino , Mutação/genética , Mioclonia/classificação , Mioclonia/genética , Transtornos Parkinsonianos/classificação , Transtornos Parkinsonianos/genéticaRESUMO
We evaluated the reliability of a translated Brazilian version of the Unified Huntington's Disease Rating Scale (UHDRS) to establish the reproducibility of the scale in a population that differs substantially from that on which the scale was originally validated. After a training period with the video and guidelines requested from the Huntington Study Group, we applied the UHDRS, except for the cognitive tests, to a group of 21 Brazilian patients with a molecular diagnosis of Huntington's disease (HD). We found a high degree of internal consistency of the motor section of the UHDRS (Cronbach's alpha= 0.841). There was a negative correlation between the total motor score and the functional assessment, the independence scale and the functional capacity. There was a positive correlation between these 3 scales of functional evaluation and a negative correlation between the age of onset of the disease and the number of CAG repeats. The behavioral scale and disease duration were not correlated with any factor. The clinical characteristics of this sample of patients as described by the UHDRS were roughly similar to those reported in the original validation studies and the correlations described were similar to those reported previously. We conclude that the Brazilian version of the UHDRS is reliable and valid to study patients with HD in the Brazilian setting, that this sample of Brazilian patients had clinical characteristics similar to those observed in other world regions, as expected, and that the clinical training method used for the application of the UHDRS was effective to insure a high degree of clinical reproducibility.
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Doença de Huntington/diagnóstico , Destreza Motora/fisiologia , Exame Neurológico/normas , Transtornos Psicomotores/diagnóstico , Adulto , Idoso , Brasil , Comparação Transcultural , Feminino , Humanos , Doença de Huntington/classificação , Doença de Huntington/genética , Masculino , Entrevista Psiquiátrica Padronizada/normas , Pessoa de Meia-Idade , Destreza Motora/classificação , Fenótipo , Transtornos Psicomotores/classificação , Transtornos Psicomotores/genética , Reprodutibilidade dos TestesRESUMO
UNLABELLED: Several genes have been mapped in families or in sporadic cases of dystonia. TOR1-A (DYT1) gene was linked to isolated dystonia. OBJECTIVE: To associate clinical information of patients with dystonia with the TOR1-A gene mutations. METHOD: Eighty-eight patients with dystonia in cervical area (focal, segmental, multifocal and generalized) were recruited at Movement Disorders Clinic of Hospital de Clínicas of the Federal University of Paraná between June of 2008 and June of 2009. They were submitted to the clinical evaluation. DNA was extract from blood and submitted at analysis to TOR1-A mutations by PCR according standard protocols. RESULTS: Two patients had c.907GAGdel mutation on TOR1-A gene. These patients, with familial history of dystonia, started his symptoms by legs and had secondary generalization. CONCLUSION: We can suggest that analysis for TOR1-A mutations should be performed only in patients with early onset, generalized and familial dystonia.
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Distonia/genética , Predisposição Genética para Doença , Chaperonas Moleculares/genética , Mutação/genética , Adolescente , Adulto , Idoso , Brasil , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Linhagem , Adulto JovemRESUMO
BACKGROUND: Several genes associated with dystonia have been identified. A mutation in one of these, THAP1 (DYT6), is linked to isolated dystonia. The aim of this study was to assess the prevalence of THAP1 gene mutations and the clinical characteristics of patients with these mutations in a clinical population in Brazil. METHODS: Seventy-four patients presenting with dystonia involving the cervical muscles and without mutations in the TOR1A (DYT1) gene or any other movement disorders were recruited at a movement disorders clinic between June 2008 and June 2009. All the patients underwent clinical examination and were screened for mutations of the THAP1 gene. RESULTS: Three patients had the novel p.Gln97Ter THAP1 nonsense mutation in heterozygosis. One of them had no family history of dystonia. Symptoms in this patient first appeared in his right arm, and the condition progressed to the generalized form. The other two patients belonged to the same family (cousins). Symptoms in the first patient started in her right arm at the age of 18 years and the condition progressed to the segmental form. The second patient, who carried the p.Arg169Gln missense mutation, developed dystonia in her left arm at the age of 6 years. The condition progressed to generalized dystonia. DISCUSSION: We conclude that THAP1 mutations are also a cause, albeit uncommon, of segmental and generalized dystonia in the Brazilian population.