High prevalence of self-reported non-motor symptoms and lack of correlation with motor severity in adult patients with idiopathic isolated dystonia.

BACKGROUND: Although abnormal movements and postures are the hallmark of dystonia, non-motor symptoms (NMS) are common and negatively affect quality of life. OBJECTIVES: The aim of this study was to screen dystonia patients for NMS and analyze their association with clinical parameters, including motor disability. METHODS: Adult patients with idiopathic isolated dystonia were interviewed and examined. Dystonia severity was evaluated with the Fahn-Marsden Dystonia Rating Scale and the presence of NMS was assessed using a list of 29 complaints. RESULTS: A hundred and two patients (63.7% female) were enrolled. Dystonia began after 20 years of age in 61.8% and was focal or segmental in 82.8% of patients. Only eight patients (7.8%) had no NMS and 59.8% reported more than five. The most prevalent NMS were pain (72.5%) and anxiety (63.7%), followed by difficulty recalling information (44.1%), sadness/anhedonia (41.2%), and difficulty falling asleep (38.2%). No correlation was found between the total number of NMS and dystonia severity (p = 0.18) or regular botulinum toxin use (p = 0.66). The majority of NMS domains correlated with each other. CONCLUSIONS: Our results confirm a high prevalence of NMS among dystonia patients, even in those with mild motor disability. The pathophysiology of NMS in dystonia remains to be completely understood.

Descriptive epidemiological study on patients with movement disorders, with emphasis on Parkinson's disease.

BACKGROUND: Knowing the epidemiological profile is relevant for improving healthcare practices. Movement disorders are neurological disorders characterized by the presence of involuntary movements. They have a negative impact on patients' quality of life. OBJECTIVES: To outline the frequencies of the different diagnoses seen among patients, along with their demographic characteristics, at a hospital in São Paulo (SP), Brazil, and to highlight the clinical aspects of those with Parkinson's disease. DESIGN AND SETTING: Retrospective descriptive epidemiological analysis at a specialized outpatient clinic in a state public hospital in São Paulo. METHODS: Patients treated at this clinic over a four-year period were analyzed. Diagnoses, demographic variables and associations with clinical aspects of Parkinson's disease were evaluated. RESULTS: Out of the 680 medical records analyzed, 58.4% related to females. Most patients were over 60 years of age, white, married and teachers. The most frequent diagnosis was Parkinson's disease, followed by essential tremor and dystonia. Parkinson's disease presented in the mixed clinical form; the most common initial symptom was tremor. The akinetic-rigid clinical form occurred in younger individuals and mostly presented with postural instability and freezing of gait in the early years of disease. CONCLUSIONS: Parkinson's disease, essential tremor and dystonia were the most frequent diagnoses. Characteristics like sex, frequency of other pathological conditions and the clinical and demographic aspects of Parkinson's disease were consistent with the data in the relevant literature.

Task-related brain activity and functional connectivity in upper limb dystonia: a functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS) study.

Significance: Dystonia is a dynamic and complex disorder. Real-time analysis of brain activity during motor tasks may increase our knowledge on its pathophysiology. Functional near-infrared spectroscopy (fNIRS) is a noninvasive method that enables the measurement of cortical hemodynamic activity in unconstrained environments. Aim: We aimed to explore the feasibility of using fNIRS for the study of task-related brain activity in dystonia. Task-related functional magnetic resonance imaging (fMRI) and resting-state functional connectivity were also analyzed. Approach: Patients with idiopathic right-upper limb dystonia and controls were assessed through nonsimultaneous fMRI and fNIRS during a finger-tapping task. Seed-based connectivity analysis of resting-state fMRI was performed in both groups. Results: The fMRI results suggest nonspecific activation of the cerebellum and occipital lobe in dystonia patients during the finger-tapping task with the affected hand. Moreover, fNIRS data show lower activation in terms of oxyhemoglobin and total hemoglobin in the frontal, ipsilateral cortex, and somatosensory areas during this task. In dystonia, both fMRI and fNIRS data resulted in hypoactivation of the frontal cortex during finger tapping with both hands simultaneously. Resting-state functional connectivity analysis suggests that the cerebellar somatomotor network in dystonia has an increased correlation with the medial prefrontal cortex and the paracingulate gyrus. Conclusions: These data suggest that unbalanced activation of the cerebellum, somatosensory, and frontal cortical areas are associated with dystonia. To our knowledge, this is the first study using fNIRS to explore the pathophysiology of dystonia. We show that fNIRS and fMRI are complementary methods and highlight the potential of fNIRS for the study of dystonia and other movement disorders as it can overcome movement restrictions, enabling experiments in more naturalistic conditions.

Patients with essential tremor can have manual dexterity and attention deficits with no impairments in other cognitive functions.

Essential tremor (ET) was long believed to be a monosymptomatic disorder. However, studies have evidenced structural changes and attention is now being focused on non-motor symptoms. The objective of the study is to describe and compare ET patients with control groups according to their cognitive functions, and secondarily, to compare their sociodemographic characteristics and other clinical features. All participants were assessed using the Fahn-Tolosa-Marin Tremor Rating Scale for the severity of tremor; a neuropsychological assessment battery and a screening questionnaire for mood and anxiety symptoms. There were no significant age and gender differences between all groups. As for neuropsychological assessment results, a significant difference was found only in the Pegboard test. We also found a significant negative correlation between a poorer cognitive test results and disease severity and a significant differences regarding depression or anxiety symptoms in patients with ET. The study results suggest that patients with ET have impaired manual dexterity and attention.

Screening of GNAL variants in Brazilian patients with isolated dystonia reveals a novel mutation with partial loss of function.

GNAL was identified as a cause of dystonia in patients from North America, Europe and Asia. In this study, we aimed to investigate the prevalence of GNAL variants in Brazilian patients with dystonia. Ninety-one patients with isolated idiopathic dystonia, negative for THAP1 and TOR1A mutations, were screened for GNAL variants by Sanger sequencing. Functional characterization of the Gαolf protein variant was performed using the bioluminescence resonance energy transfer assay. A novel heterozygous nonsynonymous variant (p. F133L) was identified in a patient with cervical and laryngeal dystonia since the third decade of life, with no family history. This variant was not identified in healthy Brazilian controls and was not described in 63,000 exomas of the ExAC database. The F133L mutant exhibited significantly elevated levels of basal BRET and severely diminished amplitude of response elicited by dopamine, that both indicate substantial functional impairment of Gαolf in transducing receptor signals, which could be involved in dystonia pathophysiology. GNAL mutations are not a common cause of dystonia in the Brazilian population and have a lower prevalence than THAP1 and TOR1A mutations. We present a novel variant that results in partial Gαolf loss of function.

Novel THAP1 variants in Brazilian patients with idiopathic isolated dystonia.

THAP1 mutations are associated with idiopathic isolated dystonia in different ethnicities, but the importance of this gene as a cause of dystonia in the Brazilian population has not been determined. The aim of this study was to investigate the prevalence of THAP1 variants in Brazilian patients with idiopathic dystonia and to describe their clinical characteristics including non-motor symptoms. One hundred and ten unrelated patients with non-TOR1A (DYT1) idiopathic isolated dystonia and family members were evaluated and screened for genetic variants. Variants with a potential pathological role were observed in 9.0% of families studied, of which four were novel. The variants were identified in approximately 12% of patients with the age of onset below 40 years. In most of the patients, the onset of the disease was before early adulthood. The upper limb was the most common site of the onset, and approximately half of the patients had dysphonia. Pain, anxiety, and sleep-onset insomnia were the most prevalent non-motor symptoms, and their prevalence was not different from that observed in THAP1-negative patients. Therefore, THAP1 variants are an important cause of dystonia among individuals with an early-onset disease and a positive family history. The phenotypical heterogeneity among patients carrying similar variants shows that other factors may be modulating the disease.

Clinical features and treatment with botulinum toxin in blepharospasm: a 17-year experience.

OBJECTIVE: It was to analyze clinical aspects of patients with blepharospasm, including outcomes of botulinum toxin treatment. Additionally, clinical characteristics of isolated blepharospasm were compared to those of blepharospasm plus other movement disorders. METHODS: Clinical data recorded during 17 years were reviewed. The variables included age, gender, age of onset, past medical history, head trauma, smoking history, family history of dystonia, severity, duration of botulinum toxin relief and adverse effects. RESULTS: A total of 125 patients were included and 75.2% were female. The mean age of onset was 54.3 years; 89.6% of the individuals started with contractions in eye region, and 39.2% of them spread to lower face or neck. Isolated blepharospasm group was compared with blepharospasm-plus group for demographic and clinical features, and therapeutic outcomes, without significant differences. Botulinum toxin treatment improved the severity of contractions (p=0.01) with low rate of side effects (14%). CONCLUSIONS: Both groups - isolated blepharospasm and blepharospasm-plus - shared similar results concerning epidemiology, clinical features and therapeutic response to botulinum toxin.

Patients with essential tremor can have manual dexterity and attention deficits with no impairments in other cognitive functions / Pacientes com tremor essencial podem apresentar prejuízo na destreza manual e déficit de atenção sem prejuízo em outras áreas da cognição

ABSTRACT Essential tremor (ET) was long believed to be a monosymptomatic disorder. However, studies have evidenced structural changes and attention is now being focused on non-motor symptoms. The objective of the study is to describe and compare ET patients with control groups according to their cognitive functions, and secondarily, to compare their sociodemographic characteristics and other clinical features. All participants were assessed using the Fahn-Tolosa-Marin Tremor Rating Scale for the severity of tremor; a neuropsychological assessment battery and a screening questionnaire for mood and anxiety symptoms. There were no significant age and gender differences between all groups. As for neuropsychological assessment results, a significant difference was found only in the Pegboard test. We also found a significant negative correlation between a poorer cognitive test results and disease severity and a significant differences regarding depression or anxiety symptoms in patients with ET. The study results suggest that patients with ET have impaired manual dexterity and attention.

RESUMO O tremor essencial (TE) era considerado como um transtorno monossintomático. Contudo estudos tem demonstrado alterações anatômicas despertando o interesse para sintomas não-motores.O objetivo do estudo é descrever e comparar pacientes com grupos controles segundo suas funções cognitivas, e secundariamente, comparar suas características demográficas e outros sintomas clínicos. Todos os participantes foram submetidos à escala de Fahn, Tolosa e Marin para avaliação da intensidade do tremor, a uma bateria neuropsicológica e a um questionário para detecção de transtorno de humor e ansiedade. Não houve diferença significativa na idade e gênero entre todos os grupos. Quanto ao resultado da avaliação neuropsicológica, foi encontrado uma diferença significativa apenas no Test Pegboard. Nós também encontramos uma correlação negativa no desempenho dos testes cognitivos e intensidade do tremor, presença de sintomas depressivos e ansiosos. Os resultados deste trabalho sugerem que pacientes com TE apresentem alteração na destreza manual e na atenção.

Clinical features and treatment with botulinum toxin in blepharospasm: a 17-year experience / Característica clínicas e tratamento com toxina botulínica em blefaroespasmo: experiência de 17 anos

OBJECTIVE: It was to analyze clinical aspects of patients with blepharospasm, including outcomes of botulinum toxin treatment. Additionally, clinical characteristics of isolated blepharospasm were compared to those of blepharospasm plus other movement disorders. METHODS: Clinical data recorded during 17 years were reviewed. The variables included age, gender, age of onset, past medical history, head trauma, smoking history, family history of dystonia, severity, duration of botulinum toxin relief and adverse effects. RESULTS: A total of 125 patients were included and 75.2% were female. The mean age of onset was 54.3 years; 89.6% of the individuals started with contractions in eye region, and 39.2% of them spread to lower face or neck. Isolated blepharospasm group was compared with blepharospasm-plus group for demographic and clinical features, and therapeutic outcomes, without significant differences. Botulinum toxin treatment improved the severity of contractions (p=0.01) with low rate of side effects (14%). CONCLUSIONS: Both groups - isolated blepharospasm and blepharospasm-plus - shared similar results concerning epidemiology, clinical features and therapeutic response to botulinum toxin.

OBJETIVOS: Analisar as características clínicas de pacientes com blefaroespasmo e os resultados do tratamento com toxina botulínica. Além disso, os pacientes foram divididos em dois grupos, blefaroespasmo isolado e blefaroespasmo associado a outros distúrbios do movimento, os quais foram comparados quanto a características clínicas e terapêuticas. MÉTODOS: Foram revisados prontuários dos últimos 17 anos. As variáveis consideradas foram idade, sexo, idade de início dos sintomas, antecedentes pessoais, história prévia de trauma crânio-encefálico, tabagismo, história familiar de distonia, gravidade do blefaroespasmo, duração do efeito da toxina botulínica e efeitos adversos. RESULTADOS: Foram incluídos 125 pacientes, dos quais 75,2% eram do sexo feminino. A média de idade do início dos sintomas era 54,3 anos; 89,6% dos pacientes tiveram início dos sintomas na região ocular e em 39,2% dos casos houve disseminação para face ou pescoço. Não houve diferenças significativas entre os grupos blefaroespasmo isolado versus blefaroespasmo-plus. O tratamento com toxina botulínica proporcionou melhora dos sintomas (p=0,01) com baixa incidência de efeitos adversos (14%). CONCLUSÕES: Ambos os grupos - blefaroespasmo isolado e blefaroespasmo-plus - apresentaram as mesmas características clínicas, epidemiológicas e resposta terapêutica à toxina botulínica.