DNAJC6 Mutations Associated With Early-Onset Parkinson's Disease.

OBJECTIVE: DNAJC6 mutations were recently described in two families with autosomal recessive juvenile parkinsonism (onset age < 11), prominent atypical signs, poor or absent response to levodopa, and rapid progression (wheelchair-bound within ∼10 years from onset). Here, for the first time, we report DNAJC6 mutations in early-onset Parkinson's disease (PD). METHODS: The DNAJC6 open reading frame was analyzed in 274 patients with early-onset sporadic or familial PD. Selected variants were followed up by cosegregation, homozygosity mapping, linkage analysis, whole-exome sequencing, and protein studies. RESULTS: We identified two families with different novel homozygous DNAJC6 mutations segregating with PD. In each family, the DNAJC6 mutation was flanked by long runs of homozygosity within highest linkage peaks. Exome sequencing did not detect additional pathogenic variants within the linkage regions. In both families, patients showed severely decreased steady-state levels of the auxilin protein in fibroblasts. We also identified a sporadic patient carrying two rare noncoding DNAJC6 variants possibly effecting RNA splicing. All these cases fulfilled the criteria for a clinical diagnosis of early-onset PD, had symptoms onset in the third-to-fifth decade, and slow disease progression. Response to dopaminergic therapies was prominent, but, in some patients, limited by psychiatric side effects. The phenotype overlaps that of other monogenic forms of early-onset PD. INTERPRETATION: Our findings delineate a novel form of hereditary early-onset PD. Screening of DNAJC6 is warranted in all patients with early-onset PD compatible with autosomal recessive inheritance. Our data provide further evidence for the involvement of synaptic vesicles endocytosis and trafficking in PD pathogenesis.

Paroxysmal exercise-induced dystonia within the phenotypic spectrum of ECHS1 deficiency.

BACKGROUND: ECHS1 encodes a mitochondrial enzyme involved in the degradation of essential amino acids and fatty acids. Recently, ECHS1 mutations were shown to cause a new severe metabolic disorder presenting as Leigh or Leigh-like syndromes. The objective of this study was to describe a family with 2 siblings affected by different dystonic disorders as a resulting phenotype of ECHS1 mutations. METHODS: Clinical evaluation, MRI imaging, genome-wide linkage, exome sequencing, urine metabolite profiling, and protein expression studies were performed. RESULTS: The first sibling is 17 years old and presents with generalized dystonia and severe bilateral pallidal MRI lesions after 1 episode of infantile subacute metabolic encephalopathy (Leigh-like syndrome). In contrast, the younger sibling (15 years old) only suffers from paroxysmal exercise-induced dystonia and has very mild pallidal MRI abnormalities. Both patients carry compound heterozygous ECHS1 mutations: c.232G>T (predicted protein effect: p.Glu78Ter) and c.518C>T (p.Ala173Val). Linkage analysis, exome sequencing, cosegregation, expression studies, and metabolite profiling support the pathogenicity of these mutations. Expression studies in patients' fibroblasts showed mitochondrial localization and severely reduced levels of ECHS1 protein. Increased urinary S-(2-carboxypropyl)cysteine and N-acetyl-S-(2-carboxypropyl)cysteine levels, proposed metabolic markers of this disorder, were documented in both siblings. Sequencing ECHS1 in 30 unrelated patients with paroxysmal dyskinesias revealed no further mutations. CONCLUSIONS: The phenotype associated with ECHS1 mutations might be milder than reported earlier, compatible with prolonged survival, and also includes isolated paroxysmal exercise-induced dystonia. ECHS1 screening should be considered in patients with otherwise unexplained paroxysmal exercise-induced dystonia, in addition to those with Leigh and Leigh-like syndromes. Diet regimens and detoxifying agents represent potential therapeutic strategies. © 2016 International Parkinson and Movement Disorder Society.

Assisted technology in Parkinson's disease gait: what's up?

BACKGROUND: Gait disturbances are prevalent and debilitating symptoms, diminishing mobility and quality of life for Parkinson's disease (PD) individuals. While traditional treatments offer partial relief, there is a growing interest in alternative interventions to address this challenge. Recently, a remarkable surge in assisted technology (AT) development was witnessed to aid individuals with PD. OBJECTIVE: To explore the burgeoning landscape of AT interventions tailored to alleviate PD-related gait impairments and describe current research related to such aim. METHODS: In this review, we searched on PubMed for papers published in English (2018-2023). Additionally, the abstract of each study was read to ensure inclusion. Four researchers searched independently, including studies according to our inclusion and exclusion criteria. RESULTS: We included studies that met all inclusion criteria. We identified key trends in assistive technology of gait parameters analysis in PD. These encompass wearable sensors, gait analysis, real-time feedback and cueing techniques, virtual reality, and robotics. CONCLUSION: This review provides a resource for guiding future research, informing clinical decisions, and fostering collaboration among researchers, clinicians, and policymakers. By delineating this rapidly evolving field's contours, it aims to inspire further innovation, ultimately improving the lives of PD patients through more effective and personalized interventions.

ANTECEDENTES: Os distúrbios da marcha são sintomas prevalentes e debilitantes, diminuindo muito a mobilidade e a qualidade de vida dos indivíduos com doença de Parkinson (DP). Embora os tratamentos tradicionais ofereçam alívio parcial, há um interesse crescente em intervenções alternativas para enfrentar esse desafio. Recentemente, um aumento notável no desenvolvimento de tecnologia assistida (TA) foi testemunhado para ajudar indivíduos com DP. OBJETIVO: Explorar o cenário crescente de intervenções de TA adaptadas para aliviar deficiências de marcha relacionadas à DP e descrever as pesquisas atuais para esse fim. MéTODOS: Nessa revisão, pesquisamos artigos em inglês publicados no PubMed de 2018 a 2023. Além disso, os resumos de cada trabalho foram lidos para assegurar a sua inclusão. Quatro pesquisadores buscaram independentemente os artigos de acordo com os critérios de inclusão e exclusão. RESULTADOS: Incluímos trabalhos que preencheram os critérios de inclusão. Identificamos as tendências em tecnologia assistiva na análise dos parâmetros da marcha em DP. Esses compreendem os sensores portáteis, análise da marcha, retroalimentação em tempo real e técnicas de pista, realidade virtual e robótica. CONCLUSãO: Essa revisão é um recurso para orientar pesquisas futuras, informar decisões clínicas e promover a colaboração entre pesquisadores, médicos e formuladores de políticas. Ao delinear os contornos deste campo em rápida evolução, pretende inspirar mais inovação, melhorando em última análise a vida dos pacientes com DP através de intervenções mais eficazes e personalizadas.

Influence of educational status on executive function and functional balance in individuals with Parkinson disease.

OBJECTIVE: This study investigated whether educational status influenced how people with Parkinson disease (PD) performed on Parts A, B, and DELTA of the Trail Making Test (TMT) and on the Berg Balance Scale (BBS). BACKGROUND: Recent studies have shown that educational status may influence cognitive and motor test performance. METHODS: We gave the TMT and the BBS to assess executive function and functional balance in 28 people with PD (Hoehn and Yahr score between 2 and 3) and 30 healthy elderly people. Participants reported their number of years of formal education. We divided each group of participants by educational status: low (4 to 10 years of education) or high (≥11 years). RESULTS: In both the PD (P=0.018) and control (P=0.003) groups, participants with low educational status performed worse on the TMT Part B than did those with high educational status. Within the PD group, the less-educated participants scored worse on the BBS than did the more educated (P<0.001); this difference was not significant between the more- and less-educated controls (P=0.976). CONCLUSIONS: Whether or not they had PD, less-educated people performed worse than more-educated people on the TMT Part B. Educational status affected executive function, but PD status did not. Among individuals with PD, educational status influenced functional balance.

Physical therapy program for cervical dystonia: a study of 20 cases.

Botulinum toxin (BTX) is the best therapeutic option inpatients with cervical dystonia (CD), but physical therapy (PT) can be added to the treatment to achieve better results. Forty of our 70 patients with CD were en-rolled in a controlled open study. Subjects were divided into two groups: G1 (intervention group comprising patients receiving BTX and PT) and G2 (control group comprising patients receiving BTX only). Both groups were assessed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the 36-Item Short-Form Health Survey (SF-36). On the TWSTRS, significant improvements in disease severity were seen in G1 and G2 but significant improvements on the pain and disability subscales were seen only in G1 patients.There was a significant difference only on the pain sub-scale between G2 and G1 following treatment. An analysis of the physical aspects of SF-36 showed significant improvement in G1 on three subscales. An intergroup difference was also seen on two subscales.Regarding emotional aspects, G1 showed a significant improvement on three subscales. A significant difference on two subscales was also seen between G2 and G1 following treatment. BTX plus PT treatment achieved symptom relief in patients with CD and improved their quality of life.

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.

Rehabilitation in patients with cerebellar ataxias.

Cerebellar ataxias comprise a heterogeneous group of diseases characterized by motor and non-motor symptoms, which can be acquired, degenerative, or have a genetic cause, such as spinocerebellar ataxias (SCA). Usually, the genetic and neurodegenerative forms of cerebellar ataxias present a progressive and inevitable worsening of the clinical picture so that rehabilitation treatment is fundamental. Rehabilitation treatment includes physical therapy, respiratory therapy, speech, voice and swallowing therapy, occupational therapy, and new technologies, such as the use of exergames. The current treatment of patients with cerebellar ataxias, especially neurodegenerative forms, genetic or not, should include these different forms of rehabilitation, with the main objective of improving the quality of life of patients.

Effect of speech therapy on quality of life in patients with spinocerebelar ataxia type 3.

BACKGROUND: Individuals with spinocerebellar ataxia type 3 (SCA3) present communication and swallowing disorders, and consequent deterioration in quality of life (QOL). OBJECTIVE: To evaluate the impact of a speech therapy rehabilitation program on the QOL of patients with SCA3. METHODS: All participants were randomly assigned to two groups, an intervention group receiving speech therapy (STG) and a control group (CG). The International Cooperative Ataxia Rating Scale scores were 32.4 ± 20.2, and the Scale for the Assessment and Rating of Ataxia scores were 11.8 ± 8.0. The intervention consisted of a 12-session speech therapy rehabilitation program with oral, pharyngeal, and laryngeal strengthening exercises-the so-called ATAXIA-Myofunctional Orofacial and Vocal Therapy (A-MOVT). They all were submitted to pre- and postintervention evaluations using the World Health Organization's Quality of Life (WHOQOL-BREF) assessment, as well as the Living with Dysarthria (LwD), Quality of Life in Swallowing Disorders (SWAL-QOL), and Food Assessment Tool (EAT-10). RESULTS: The study sample consisted of 48 patients with SCA3 (STG = 25; CG = 23), mean age was 47.1 ± 11.4 years; mean age at symptom onset was 36.9 ± 11.3 years; disease duration was 11.9 ± 13.3 years. After the 3-month intervention, there were significant changes in the QOL in the STG compared with the CG, when assessed by the LwD (179.12 ± 62.55 vs. 129.88 ± 51.42, p < 0.001), SWAL-QOL (869.43 ± 153.63 vs. 911.60 ± 130.90, p = 0.010), and EAT-10 (5.16 ± 7.55 vs. 2.08 ± 3.85, p = 0.018). CONCLUSIONS: Patients with SCA3 should receive continuous speech therapy as part of the A-MOVT program, because therapy helps to improve difficulty swallowing and dysarthria.

ANTECEDENTES: Indivíduos com ataxia espinocerebelar tipo 3 (AEC3) apresentam distúrbios da comunicação e deterioração da deglutição e, consequentemente, na qualidade de vida (QV). OBJETIVO: Avaliar o impacto de um programa de reabilitação fonoaudiológica na QV em pacientes com AEC3. MéTODOS: Todos os participantes foram alocados aleatoriamente em dois grupos, um grupo intervenção que recebeu terapia fonoaudiológica (GTF) e um grupo controle (GC). As pontuações das escalas: International Cooperative Ataxia Rating Scale (ICARS) foram 32,4 ± 20,2 e da Scale for the Assessment and Rating of Ataxia (SARA) foram 11,8 ± 8,0. A intervenção consistiu em um programa de reabilitação fonoaudiológica de 12 sessões composto por exercícios de fortalecimento oral, faríngeo e laríngeo - denominados ATAXIA - Terapia Miofuncional Orofacial e Vocal (A-TMOV). Todos foram submetidos a avaliações pré e pós-intervenção por meio dos protocolos World Health Organization's Quality of Life (WHOQOL-BREF), Vivendo com Disartria (VcD), Quality of Life in Swallowing Disorders (SWAL-QOL) e Food Assessment Tool (EAT-10). RESULTADOS: A amostra foi composta por 48 pacientes com AEC3 (25 no GTF e 23 no GC), média de idade 47,1 ± 11,4anos; média de idade de início dos sintomas 36,9 ± 11,3anos; duração da doença 11,9 ± 13,3anos. Após intervenção de três meses, houve mudanças significativas na QV no GTF em comparação com o GC quando avaliado pelo VcD (179,12 ± 62,55 versus129,88 ± 51,42, p < 0,001), SWAL-QOL (869,43 ± 153,63 versus 911,60 ± 130,90, p = 0,010), EAT-10 (5,16 ± 7,55 versus 2,08 ± 3,85, p = 0,018). CONCLUSõES: Pacientes com AEC3 devem receber terapia fonoaudiológica contínua como parte do programa A-TMOV, pois a terapia ajuda a melhorar a dificuldade de deglutição e a disartria.

Guidelines for Parkinson's disease treatment: consensus from the Movement Disorders Scientific Department of the Brazilian Academy of Neurology - motor symptoms.

The treatment of Parkinson's disease (PD) is challenging, especially since it is considered highly individualized. The Brazilian Academy of Neurology has recognized the need to disseminate knowledge about the management of PD treatment, adapting the best evidence to the Brazilian reality. Thus, the main published treatment guidelines were reviewed based on the recommendations of group from the Movement Disorders Scientific Department of the Brazilian Academy of Neurology.

Neuropathologic Findings in a Patient With Juvenile-Onset Levodopa-Responsive Parkinsonism Due to ATP13A2 Mutation.

OBJECTIVE: To describe the postmortem neuropathologic findings of a patient with Kufor Rakeb syndrome (KRS) due to ATP13A2 mutation. KRS is characterized by juvenile-onset levodopa-responsive parkinsonism associated with pyramidal signs, supranuclear gaze palsy, and cognitive impairment. METHODS: A detailed neuropathologic analysis of the brain was performed. The patient had a genetically confirmed ATP13A2 homozygous missense mutation and died at age 38 years, which was 26 years after the onset of his symptoms. RESULTS: The main brain neuropathologic findings were widespread neuronal and glial lipofuscin accumulation with no Lewy body-type inclusions and absence of α-synuclein-positive, tau-positive, ß-amyloid-positive, and TDP-43 protein-positive pathologies. Sparse iron deposits were observed in several brain areas, but no obvious axonal spheroids were identified. DISCUSSION: This is to our knowledge the first KRS postmortem neuropathologic description. Iron deposits were found but not associated with increased axonal spheroids, as frequently observed in neurodegeneration with brain iron accumulation. ATP13A2 mutations have been described in patients with neuronal ceroid lipofuscinosis (CLN). Moreover, animal models with these mutations develop neurodegenerative disorders with CLN pathology. Therefore, our findings support that ATP13A2 mutations may be considered a genetic etiology of neuronal lipofuscinosis.

Effects of resistance training on postural control in Parkinson's disease: a randomized controlled trial.

BACKGROUND: Postural instability affects Parkinson's disease (PD) patients' postural control right from the early stages of the disease. The benefits of resistance training (RT) for balance and functional capacity have been described in the literature, but few studies have been conducted showing its effects on PD patients' postural control. OBJECTIVE: To investigate the effects of a three-month RT intervention on static posturography (SP) measurements and clinical functional balance assessment among PD patients. METHODS: Seventy-four patients were randomly assigned to a three-month RT intervention consisting of using weightlifting machines at a gym (gym group) or RT consisting of using free weights and elastic bands (freew group), or to a control group. The participants were evaluated at baseline, three months and six months. We evaluated changes of SP measurements under eyes-open, eyes-closed and dual-task conditions (primary endpoint), along with motor performance and balance effects by means of clinical scales, dynamic posturography and perceptions of quality of life (secondary endpoints). RESULTS: There were no significant interactions in SP measurements among the groups. Unified Parkinson Disease Rating Scale (UPDRS-III) motor scores decreased in both RT groups (p<0.05). Better perceived quality of life for the mobility domain was reported in the gym group while functional balance scores improved in the freew group, which were maintained at the six-month follow-up (p<0.05). CONCLUSIONS: This study was not able to detect changes in SP measurements following a three-month RT intervention. Both RT groups of PD patients showed improved motor performance, with positive balance effects in the freew group and better perceived quality of life in the gym group.

Generation of 5 hiPSC lines derived from three unrelated idiopathic Parkinson disease patients and two unrelated healthy control individuals.

We describe generation of human induced pluripotent stem cell (hiPSC) lines of three unrelated idiopathic late onset Parkinson disease patients and two healthy controls above 60 years of age without neurological diseases nor Ashkenazi ancestry. Human iPSC were derived from peripheral blood-erythroblasts using integration free episomal plasmids carrying four reprogramming factors OCT4, SOX2, c-MYC, KLF4 and BCL-XL. The hiPSC lines were characterized according to established criteria.

Generation of three human induced pluripotent stem cell (hiPSC) lines derived from one Gaucher disease patient with Parkinson's disease and two unrelated Parkinson's disease patients with GBA mutations.

We describe the generation and characterization of hiPSC lines of one type 1-Gaucher disease patient with Parkinson's disease and two unrelated Parkinson's disease patients heterozygous for GBA mutations. Human iPSCs were derived from lymphocytes reprogrammed with Sendai virus carrying the reprogramming factors OCT3/4, SOX2, KLF4 and MYC. The hiPSC lines were characterized according to established criteria, and retained the original GBA mutations found in the respective patients.

Is virtual reality beneficial for dual-task gait training in patients with Parkinson's disease? A systematic review.

This systematic review examined the evidence about the effects of virtual reality (VR) on dual-task gait training in Parkinson's disease (PD). METHODS: this study (PROSPERO registration CRD42019114736) aimed to answer the question: "Is VR beneficial for dual-task gait training in patients with PD?" We searched for studies from 2008 to 2018 on Medline/PubMed and Web of Science/Web of knowledge databases. The keywords were Parkinson AND gait training AND virtual reality OR Parkinson AND gait training AND game. A total of 55 articles were retrieved, of which 11 systematic reviews, 11 opinions, letters to the editor, posters or conferences abstracts and 17 studies not evaluating the effects of VR gait training were excluded. Three further studies addressing VR dual-task gait training in PD (found in references of studies selected) were also included. Therefore, 19 studies were included and analysed. RESULTS: all studies reported gait improvement after VR training. Many clinical scales were used, hampering comparison of the effects of each protocol. CONCLUSION: VR dual-task gait training should be part of rehabilitation protocols for PD. The studies showed that VR training was effective, although specific guidelines have not yet been established.

Essa revisão sistemática examinou as evidências sobre os efeitos da realidade virtual (RV) no treinamento de marcha com tarefa-dupla na doença de Parkinson (DP). MÉTODOS: esse estudo (registro PROSPERO: CRD42019114736) visou responder à questão: "A RV é benéfica no treinamento de marcha com tarefa-dupla em pacientes com DP?" A busca, de 2008 a 2018, foi feita nos bancos de dados Medline/PubMed e Web of Science/Web of Knowledge. Os descritores foram Parkinson, treinamento de marcha, realidade virtual e jogos eletrônicos. Foram encontrados 55 artigos e eliminadas 11 revisões sistemáticas, 11 cartas ao editor, resumos de pôsteres ou conferências e 17 estudos que não avaliaram os efeitos do treinamento da marcha em RV. Três outros estudos (encontrados nas referências dos estudos selecionados) foram incluídos porque também abordaram o treinamento de marcha com dupla tarefa de RV em DP. Portanto, 19 estudos foram incluídos e analisados. RESULTADOS: todos os estudos relataram melhora da marcha após o treinamento com RV. Muitas escalas clínicas foram usadas e foi difícil comparar os efeitos de cada protocolo. CONCLUSÃO: RV deve fazer parte dos protocolos de reabilitação em DP. O treinamento com RV é eficaz, embora recomendações específicas ainda não tenham sido estabelecidas.

Relationship Between Posturography, Clinical Balance and Executive Function in Parkinson´s Disease.

This study aimed to evaluate the relationship between posturography, clinical balance, and executive function tests in Parkinson´s disease (PD). Seventy-one people participated in the study. Static posturography evaluated the center of pressure fluctuations in quiet standing and dynamic posturography assessed sit-to-stand, tandem walk, and step over an obstacle. Functional balance was evaluated by Berg Balance Scale, MiniBESTest, and Timed Up and Go test. Executive function was assessed by Trail Making Test (TMT) and semantic verbal fluency test. Step over obstacle measures (percentage of body weight transfer and movement time) were moderately correlated to Timed Up and Go, part B of TMT and semantic verbal fluency (r > 0.40; p < 0.05 in all relationships). Stepping over an obstacle assesses the responses to internal perturbations. Participants with shorter movement times and higher percentage of body weight transfer (higher lift up index) on this task were also faster in Timed Up and Go, part B of TMT, and semantic verbal fluency. All these tasks require executive function (problem solving, sequencing, shifting attention), which is affected by PD and contribute to postural assessment.

Cross-cultural adaptation and validation of the International Cooperative Ataxia Rating Scale (ICARS) to Brazilian Portuguese.

OBJECTIVE: The clinical assessment of patients with ataxias requires reliable scales. We aimed to translate, adapt and validate the International Cooperative Ataxia Rating Scale (ICARS) into Brazilian Portuguese. METHODS: The steps of this study were forward translation, translation synthesis, backward translation, expert committee meeting, preliminary pilot testing and final assessment. Thirty patients were enrolled in the preliminary pilot testing and 61 patients were evaluated for construct validity, internal consistency, intra- and inter-rater reliability and external consistency. RESULTS: This study showed good validity of the construct and high internal consistency for the full scale, except for the oculomotor domain (Cronbach's alpha = 0.316, intraclass correlation coefficients intra- = 82.4% and inter- = 79.2%). A high correlation with the Scale for the Assessment and Rating of Ataxia was observed. We found good intra-rater agreement and relative inter-rater disagreement, except in the posture and gait domain. CONCLUSION: The present ICARS version is adapted for the Brazilian culture and can be used to assess our ataxic patients.

Defining spasticity: a new approach considering current movement disorders terminology and botulinum toxin therapy.

Spasticity is a symptom occurring in many neurological conditions including stroke, multiple sclerosis, hypoxic brain damage, traumatic brain injury, tumours and heredodegenerative diseases. It affects large numbers of patients and may cause major disability. So far, spasticity has merely been described as part of the upper motor neurone syndrome or defined in a narrowed neurophysiological sense. This consensus organised by IAB-Interdisciplinary Working Group Movement Disorders wants to provide a brief and practical new definition of spasticity-for the first time-based on its various forms of muscle hyperactivity as described in the current movement disorders terminology. We propose the following new definition system: Spasticity describes involuntary muscle hyperactivity in the presence of central paresis. The involuntary muscle hyperactivity can consist of various forms of muscle hyperactivity: spasticity sensu strictu describes involuntary muscle hyperactivity triggered by rapid passive joint movements, rigidity involuntary muscle hyperactivity triggered by slow passive joint movements, dystonia spontaneous involuntary muscle hyperactivity and spasms complex involuntary movements usually triggered by sensory or acoustic stimuli. Spasticity can be described by a documentation system grouped along clinical picture (axis 1), aetiology (axis 2), localisation (axis 3) and additional central nervous system deficits (axis 4). Our new definition allows distinction of spasticity components accessible to BT therapy and those inaccessible. The documentation sheet presented provides essential information for planning of BT therapy.

Endonasal approach of salpingopharyngeus muscle for the treatment of ear click related to palatal tremor.

Palatal tremor (PT) is a rare disease associated with rhythmic movements of the soft palate. It can be separated into two distinct clinical entities: symptomatic and essential. Most patients with essential PT complain of the rhythmic ear clicks and in some cases tinnitus, but usually have an uneventful medical history. Symptomatic PT patients are often unaware of the palatal movements and have symptoms and signs of brainstem or cerebellar dysfunction. We describe the case of a 25-year-old patient who developed severe essential PT, with very distressing bilateral objective tinnitus, constantly perceived as ear clicks. Several oral medications were prescribed with poor results. No significant improvement was obtained with repetitive injections of botulinum toxin type A (BTX A) distributed in soft palate muscles. Because of the continuous tinnitus and its impact on the patient's quality of life, chemical denervation of the salpingopharyngeus muscles, which is involved in the production of tinnitus, with BTX A was performed endonasally under endoscopic guidance. The result was very satisfactory. Tinnitus due to essential PT may be satisfactorily treated by endonasal injection of BTX into the salpingopharyngeus and palatopharyngeus muscles.

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.