Development and Validation of the Dystonia-Pain Classification System: A Multicenter Study.

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.

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.

Botulinum Toxin and Deep Brain Stimulation in Dystonia.

Deep Brain Stimulation (DBS) is a recognized treatment for different dystonia subtypes and has been approved by the Food and Drug Administration (FDA) since 2003. The European Federation of Neurological Societies (EFNS) and the International Parkinson and Movement Disorders Society (MDS) recommend DBS for dystonia after failure of botulinum toxin (BoNT) and other oral medications for dystonia treatment. In addition, several long-term studies have demonstrated the continuous efficacy of DBS on motor and quality of life (QoL) scores. However, there are only a few reports comparing the overall impact of surgical treatment in BoNT protocols (e.g., dosage and number of selected muscles before and after surgery). This retrospective multicenter chart-review study analyzed botulinum toxin total dosage and dosage per muscle in 23 dystonic patients before and after DBS surgery. The study's primary outcome was to analyze whether there was a reduction in BoNT dosage after DBS surgery. The mean BoNT dosages difference between baseline and post-surgery was 293.4 units for 6 months, 292.6 units for 12 months, and 295.2 units at the last visit. The median total dose of BoNT in the preoperative period was 800 units (N = 23). At the last visit, the median was 700 units (p = 0.05). This represents a 12.5% reduction in BoNT median dosage. In conclusion, despite the limitations of this retrospective study, there was a significant reduction in BoNT doses after DBS surgery in patients with generalized dystonia.

How I treat Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a complex neurodegenerative condition. Treatment strategies through all stages of disease progression could affect quality of life and influence the development of future complications, making it crucial for the clinician to be on top of the literature. OBJECTIVE: This paper reviews the current treatment of PD, from early to advanced stages. METHODS: A literature review was conducted focusing on the treatment of PD, in the different stages of progression. RESULTS: Every individual with a new diagnosis of PD should be encouraged to start exercising regularly. In the early stage, treatment should focus on using the lowest dose of levodopa or combination therapy that provides maximum functional capacity, and does not increase the risk of complications, such as peak dose dyskinesias and impulse control disorders. At the moderate and advanced stages, motor fluctuations and complications of treatment dominate the picture, making quality of life one important issue. Rehabilitation programs can improve motor symptoms and should be offered to all patients at any stage of disease progression. CONCLUSION: Many factors need to be considered when deciding on the best treatment strategy for PD, such as disease progression, presence of risk factors for motor and behavioral complications, potential side effects from dopaminergic therapy and phenotypical variabilities. Treatment should focus on functional capacity and quality of life throughout the whole disease course.

Movement Disorders in Brazil: the seminal contributions of Luiz Augusto Franco de Andrade and Egberto Reis Barbosa.

The major advances in the area of movement disorders in Brazil in recent years were driven by the work of Luiz Augusto Franco de Andrade and Egberto Reis Barbosa. This historical review describes the contributions made by these researchers, physicians, and educators to the development of this field in Brazil.

Roberto Melaragno's scientific contributions to Brazilian Neurology.

Roberto Melaragno Filho, an associate professor of neurology at the School of Medicine of Universidade de São Paulo and head of the neurology service at Hospital do Servidor Público Estadual Francisco Morato Oliveira (HSPE-FMO), had a significant scientific career. He is recognized as a reference in the 20th century Brazilian neurology in addition to having a notable international career.

Non-invasive brain stimulation and kinesiotherapy for treatment of focal dystonia: Instrumental analysis of three cases.

Dystonia is a disabling movement disorder characterized by co-contraction of antagonist and agonist muscles, leading to abnormal sustained postures and impaired motor control. Cervical Dystonia (CD) and Hand Focal Dystonia (HFD) have been the most common forms of focal dystonia (FD). Do Non-Invasive Brain Neuromodulation (NIBS) such as Transcranial Direct Current Stimulation (tDCS) and repetitive Transcranial Magnetic Stimulation (rTMS) modulate the excitability of the connections between the motor cortical areas and may represent a therapeutic alternative for focal dystonia? Herein, we reported three cases of focal dystonia, two of them with cervical dystonia (CD) and one with hand focal dystonia (HFD), treated with NIBS combined to kinesiotherapy. The patients were daily submitted to 15 sessions of NIBS combined simultaneously with kinesiotherapy. CD patients were treated with tDCS (2 mA, 20 min, over the primary motor cortex), and HFD patient with rTMS (1 Hz, 1200 pulses, 80% of resting motor threshold, over the premotor cortex). For the CD patient's assessment, the Modified Toronto Scale for Cervical Dystonia Assessment (MTS), quiet balance test, and visual postural assessment were applied to observe the therapeutic effects. Quality handwriting analysis, tremor acceleration amplitudes, and the Wrinter's Cramp Rating Scale (WCRS) were used to assess the NIBS effect on HFD symptoms. Patients were evaluated before (pretest), immediately after (posttest), and three months after treatment (retention). NIBS associated with kinesiotherapy produced a long-term improvement of dystonia symptoms in all three patients. rTMS and tDCS associated with kinesiotherapy showed to be useful and safe to relief the dystonia symptoms in individuals with different types of focal dystonia with distinct functional disorders. SIGNIFICANCE: The combined use of these intervention strategies seems to optimize and anticipate satisfactory clinical results in these neurological conditions, characterized by its difficult clinical management.

The prevalence of PRKRA mutations in idiopathic dystonia.

INTRODUCTION: DYT-PRKRA (DYT16) is considered a rare cause of dystonia-parkinsonism. The significance of this gene as a cause of dystonia and its phenotypical characterization must be determined in larger cohorts. We aimed to investigate the role of PRKRA in patients with dystonia. METHODS: We sequenced PRKRA in 153 unrelated Brazilian patients with idiopathic dystonia. The frequency of novel missense variants was investigated in healthy Brazilian controls and in public databases. Homozygosity in the PRKRA region was assessed through polymorphic markers. RESULTS: PRKRA variants were identified in seven probands with isolated dystonia, including a novel c.C795A variant in compound heterozygosity with the previously described c.C665T variant. Heterozygosity in the gene region was observed in two probands who were homozygous for c.C665T, indicating that this mutation originated from independent events, suggesting a hotspot. CONCLUSION: PRKRA is not an unusual cause of idiopathic dystonia. In this cohort, it was responsible for 4.5% of the total of cases (4.9% of the isolated dystonia cases). The most common phenotype was early-onset isolated focal dystonia followed by generalization, parkinsonism was not observed. This is first report of PRKRA causing adulthood-onset dystonia. Screenings of large cohorts are recommended to investigate the role of this gene in isolated dystonia, as well as in dystonia-parkinsonism cases worldwide.

How I treat Parkinson's disease / Como eu trato a doença de Parkinson

ABSTRACT Background: Parkinson's disease (PD) is a complex neurodegenerative condition. Treatment strategies through all stages of disease progression could affect quality of life and influence the development of future complications, making it crucial for the clinician to be on top of the literature. Objective: This paper reviews the current treatment of PD, from early to advanced stages. Methods: A literature review was conducted focusing on the treatment of PD, in the different stages of progression. Results: Every individual with a new diagnosis of PD should be encouraged to start exercising regularly. In the early stage, treatment should focus on using the lowest dose of levodopa or combination therapy that provides maximum functional capacity, and does not increase the risk of complications, such as peak dose dyskinesias and impulse control disorders. At the moderate and advanced stages, motor fluctuations and complications of treatment dominate the picture, making quality of life one important issue. Rehabilitation programs can improve motor symptoms and should be offered to all patients at any stage of disease progression. Conclusion: Many factors need to be considered when deciding on the best treatment strategy for PD, such as disease progression, presence of risk factors for motor and behavioral complications, potential side effects from dopaminergic therapy and phenotypical variabilities. Treatment should focus on functional capacity and quality of life throughout the whole disease course.

RESUMO Antecedentes: A doença de Parkinson (DP) é uma doença neurodegenerativa complexa. As estratégias de tratamento ao longo de todos os estágios da evolução podem influenciar a qualidade de vida e o desenvolvimento de futuras complicações e, portanto, devem ser devidamente conhecidas pelos médicos que assistem o paciente. Objetivo: Neste artigo são revistos os tratamentos atuais para a DP, desde o estágio inicial até os estágios avançados. Métodos: Uma revisão da literatura foi realizada com enfoque em diferentes estágios da doença. Resultados: Todos os pacientes que recebem o diagnóstico de DP devem ser orientados a praticar atividades físicas regularmente. Em fase inicial do tratamento a estratégia consiste em usar doses mínimas de levodopa ou terapias combinadas que propiciem máxima capacidade funcional, que não aumentem o risco de complicações motoras, tais como discinesias induzidas por levodopa, ou não motoras, como transtornos do controle do impulso. Em estágio moderado ou avançado da doença, complicações como flutuações motoras e discinesias tornam-se relevantes e devem ser manejadas adequadamente. Programas de reabilitação devem ser oferecidos para os pacientes em todos os estágios da DP. Conclusões: Vários fatores devem ser considerados ao se escolher a melhor estratégia para o tratamento da DP. Entre eles destacam-se: fatores de risco para o desenvolvimento de complicações motoras e comportamentais, potenciais efeitos colaterais da terapia dopaminérgica e variabilidade fenotípica. O objetivo das estratégias de tratamento ao longo de toda a evolução da doença é a melhoria da capacidade funcional e da qualidade de vida dos pacientes.

Speech disorders did not correlate with age at onset of Parkinson's disease.

Speech disorders are common manifestations of Parkinson´s disease. Objective To compare speech articulation in patients according to age at onset of the disease. Methods Fifty patients was divided into two groups: Group I consisted of 30 patients with age at onset between 40 and 55 years; Group II consisted of 20 patients with age at onset after 65 years. All patients were evaluated based on the Unified Parkinson's Disease Rating Scale scores, Hoehn and Yahr scale and speech evaluation by perceptual and acoustical analysis. Results There was no statistically significant difference between the two groups regarding neurological involvement and speech characteristics. Correlation analysis indicated differences in speech articulation in relation to staging and axial scores of rigidity and bradykinesia for middle and late-onset. Conclusions Impairment of speech articulation did not correlate with age at onset of disease, but was positively related with disease duration and higher scores in both groups.

Voice telerehabilitation in Parkinson's disease. / Telerreabilitação vocal na doença de Parkinson.

UNLABELLED: Parkinson's disease (PD) is a neurodegenerative condition associated with motor, neuropsychological, sensorial, and vocal symptoms. It has been suggested that eventual obstacles faced by many patients to reach speech therapy rehabilitation centers could be overcome with the use of synchronous telerehabilitation (real time) approach employing communication technologies. PURPOSE: To investigate the efficacy of vocal telerehabilitation in PD patients. METHODS: Twenty patients diagnosed with PD and with vocal complaints participated in this study. Patients were evaluated by videoconference (Adobe Connect 8) before and after treatment. Evaluation method consisted of perceptual analysis of vocal quality measured by the GRBASI scale. Treatment was conducted following the extended version of Lee Silverman method (LSVT-X). At the end of treatment all patients were requested to fill a questionnaire to assess their experience with telerehabilitation. RESULTS: Analysis revealed decrease in magnitude of voice quality changes after the intervention, indicating improvement of vocal pattern. All patients reported satisfaction and preference for telerehabilitation compared to face-to-face rehabilitation, as well as positive perception of audio and video. Some technological adversities have been identified but did not prevent the approaches to assessment and treatment. CONCLUSION: Present results suggest that telerehabilitation methods can be considered as an effective treatment for speech symptoms associated with PD and can be indicated to patients presenting limited access to speech therapy centers and technological readiness.

Telerehabilitation in Parkinson's disease: Influence of cognitive status.

BACKGROUND: The need for efficacy in voice rehabilitation in patients with Parkinson's disease is well established. Given difficulties traveling from home to treatment centers, the use of telerehabilitation may represent an invaluable tool for many patients. OBJECTIVE: To analyze the influence of cognitive performance on acceptance of telerehabilitation. METHODS: Fifty patients at stages 2-4 on the Hoehn-Yahr scale, aged 45-87 years old, with cognitive scores of19-30 on the Mini-Mental State Examination, and 4-17 years of education were enrolled. All patients were submitted to evaluation of voice intensity pre and post in-person treatment with the Lee Silverman Voice Treatment (LSVT) and were asked to fill out a questionnaire regarding their preferences between two options of treatment and evaluating basic technological competence. RESULTS: Comparisons between pre and post-treatment values showed a mean increase of 14dBSPL in vocal intensity. When asked about potential acceptance to participate in future telerehabilitation, 38 subjects agreed to take part and 12 did not. For these two groups, 26% and 17% self-reported technological competence, respectively. Agreement to engage in remote therapy was positively associated with years of education and cognitive status. CONCLUSION: Responses to the questionnaire submitted after completion of traditional in-person LSVT showed that the majority of patients (76%) were willing to participate in future telerehabilitation. Age, gender, disease stage and self-reported basic technological skills appeared to have no influence on the decision, whereas other factors such as cognitive status and higher school education were positively associated with acceptance of the new therapy approach.

EMBASAMENTO: A eficácia na reabilitação da voz em pacientes com doença de Parkinson está bem estabelecida. Tendo em vista as dificuldades de lidar com a locomoção de casa para centros de tratamento, o uso da telerreabilitação pode representar uma ferramenta inestimável para muitos pacientes. OBJETIVO: Analisar a influência do desempenho cognitivo na aceitação da telerreabilitação. MÉTODOS: Participaram cinquenta pacientes em estágios 2-4 de acordo com a escala de Hoehn-Yahr, com idade entre 45 e 87 anos, escores cognitivos de 19 a 30 no Mini-Exame do Estado Mental e escolaridade entre 4-17 anos. Todos foram submetidos à avaliação da intensidade da voz antes e depois do tratamento pelo Lee Silverman Voice Treatment (LSVT) e foram convidados a responder um questionário sobre suas preferências entre duas opções de tratamento. RESULTADOS: O tratamento resultou em aumento médio de 14dBNPS. Quando questionados sobre a possibilidade de aceitação para participar de um futuro programa de telerreabilitação, 38 indivíduos concordaram e 12 não. Em relação a estes dois grupos, a competência tecnológica foi referida em 26% e 17%, respectivamente. A aceitação à telerreabilitação foi positivamente relacionada com anos de estudo e estado cognitivo. CONCLUSÃO: As respostas ao Questionário após a conclusão do LSVT tradicional mostraram que a maioria dos pacientes (76%) concordaria em participar de uma futura telerreabilitação. Idade, sexo, estágio da doença ou competência tecnológica não pareceu influenciar na adesão à telerreabilitação enquanto que outros fatores, como estado cognitivo e anos de escolaridade foram positivamente relacionados com a aceitação da nova forma de terapia.

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.

[Treatment of vocal symptoms in Parkinson's disease: the Lee Silverman method]. / Tratamento dos distúrbios da voz na doença de Parkinson: o método Lee Silverman.

Mild changes in voice quality and articulation of speech may be seen in early phases of Parkinson's disease (PD). Voice and speech disturbances in PD constitute a hypocinetic dysarthria or dysarthrophonia and are characterized by monotony and reduced intensity of voice, imprecise articulation and disturbances of rhythm. Favorable results with an intensive method (Lee Silverman Voice Treatment) for the treatment of voice disturbances in PD were recently reported. The main goal of the method is to augment vocal intensity through the increment of phonatory effort. The purpose of the present study was to characterize vocal abnormalities (hoarseness, breathiness, articulatory pattern and inteligibility) in a group of patients with PD and to evaluate the therapeutic efficacy of the Lee Silverman method. Acoustic as well as perceptive-auditory analysis showed statistically significant differences between pre and post treatment groups. Although the articulatory pattern has not considerably changed, the benefits obtained with the improvement in vocal quality positively influenced overall quality of oral communication.

A case of primary spinal myoclonus: clinical presentation and possible mechanisms involved.

Spinal myoclonus is a rare movement disorder characterized by myoclonic involvement of a group of muscles supplied by a few contiguous segments of the spinal cord. Structural lesions are usually the cause, but in primary spinal myoclonus the etiology remains unknown. We present the case of a 26-year-old woman with cervical spinal myoclonus in which both clinical and electromyographic findings pointed to the segment C1-C3 as the origin of the myoclonus. Laboratorial examinations were normal and no structural lesion was found in magnetic resonance imaging (MRI). Botulinum toxin type A was injected in infrahyoid muscles and cervical paraspinal musculature. The patient remained free of symptoms for almost five months. The pathophysiology of spinal myoclonus remains speculative, but there is evidence that various possible mechanisms can be involved: loss of inhibitory function of local dorsal horn interneurons, abnormal hyperactivity of local anterior horn neurons, aberrant local axons re-excitations and loss of inhibition from suprasegmentar descending pathways.

[Bilateral hemifacial spasm: case report]. / Espasmo hemifacial bilateral: relato de caso.

Bilateral hemifacial spasm (BHS) is a rare focal movement disorder often associated with vascular compression of both facial nerves. The contractions are usually asymmetric and asynchronous. Typically, one side is affected first and there is a long but variable interval for the symptoms on the other side to occur. BHS must be differentiated from other conditions including blefarospasm, facial myokymia, facial tics, oromandibular dystonia, and hemimasticatory spasm. The most successful and non-invasive symtomatic treatment is botulinum toxin injections but microvascular decompression surgery is another therapeutic option. We report the case of a 70 years old man with bilateral hemifacial spasms and present a brief review of the literature.

[Leptomeningeal carcinomatosis as the first clinical manifestation of lung adenocarcinoma: case report]. / Carcinomatose leptomeníngea como primeira manifestação de adenocarcinoma pulmonar: relato de caso.

Leptomeningeal carcinomatosis is a neurological complication of several systemic tumors and is characterized by multifocal invasion of the meninges by neoplastic cells. It is estimated that 5% of all patients with cancer will present leptomeningeal carcinomatosis at some time during the course of the illness. Clinical manifestations are heterogeneous and present with signs and symptoms related to involvement of multiple areas of the nervous system, particularly cranial nerves and spinal roots. The diagnosis is based on suggestive clinical findings, cerebrospinal fluid (CSF) testing and imaging studies. The most informative findings come from CSF where the presence of neoplastic cells is definitive for the diagnosis. The purpose of this report is to describe, along with a review of the literature, a clinical case of a 42 years old man in whom the first clinical signs of a lung cancer manifested with symptoms suggestive of meningeal involvement.

Movement disorders induced by peripheral trauma.

Movement disorders induced by central nervous system trauma are well recognized. However, over the last few years, attention has been drawn to the role of peripherally induced movement disorders. We describe three patients presenting respectively dystonia, tremor and choreoathetosis associated with tremor and dystonia of the body parts previously exposed to traumatic injuries. Pathophysiological mechanisms underlying these phenomena are not entirely known, but functional changes in afferent neuronal input to the spinal cord and secondary affection of higher brain stem and subcortical centers are probably involved.

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.