Estimulação cerebral profunda para o tratamento da distonia primária generalizada e distonia cervical / Deep brain stimulation for the treatment of primary generalized dystonia and cervical dystonia

INTRODUÇÃO: A distonia é um distúrbio neurológico caracterizado por contrações musculares involuntárias, responsáveis por posturas e movimentos anormais. Sua expressão clínica é determinada pela gravidade e distribuição dos músculos envolvidos, desde variações focais e segmentares mais leves, a casos mais graves de manifestação generalizada. No Brasil, no âmbito do Sistema Único de Saúde (SUS), há um Protocolo Clínico e Diretrizes Terapêuticas sobre o cuidado de Distonia e Espasmo Hemifacial que preconiza a utilização da Toxina Botulínica Tipo A (TBA). A estimulação cerebral profunda (Deep Brain Stimulation - DBS) é um procedimento cirúrgico utilizado no tratamento de várias doenças neurológicas, normalmente em casos refratários à terapia usual. A DBS consiste na implantação de um dispositivo médico para fornecer estimulação elétrica a regiões específicas do cérebro. Tendo em vista que existem produtos de saúde aprovados pela Anvisa para realização da DBS e que o procedimento já está disponível no SUS para determinadas condições, o presente relatório foi desenvolvido com o objetivo de compreender a viabilidade de ampliação de uso desse procedimento no SUS para o tratamento de distonia primária generalizada e distonia cervical. PERGUNTA DE PESQUISA: O uso da DBS é eficaz, seguro e custo-efetivo para o tratamento de distonia primária generalizada e distonia cervical em pacientes adultos e pediátricos refratários ao tratamento convencional? EVIDÊNCIAS CLÍNICAS: Foi realizada uma revisão sistemática a partir de buscas nas bases de dados MEDLINE (via Pubmed), EMBASE, Cochrane Library, LILACS, IBECS, BRISA (via BVS), considerando o tratamento de distonia primária generalizada e distonia cervical com o procedimento de estimulação cerebral profunda. Foram estabelecidos critérios de elegibilidade abrangentes devido à escassez de estudos disponíveis na literatura científica. Os estudos foram avaliados quanto ao risco de viés com a ferramenta Cochrane Risk of Bias Tool ­ ROB 2.0 para Ensaio Clínico Randomizado (ECR) e a ferramenta Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) para os estudos observacionais. A qualidade geral da evidência foi avaliada utilizando a abordagem GRADE (Grading of Recommendatons Assessment, Development and Evaluaton). Para distonia primária generalizada, foram incluídos 17 estudos que envolveram 350 pacientes, entre crianças e adultos. Entre os estudos identificados um era ensaio clínico randomizado (ECR) que comparou DBS e sham; os demais estudos eram ensaios clínicos não randomizados (n=4) ou observacionais (estudos de coorte (n=10) e séries de casos (n=2). O ECR analisado incluiu tanto crianças quanto adultos e avaliou no total 40 pacientes. Os resultados apresentados foram positivos na redução do comprometimento motor (redução de 39,3%) e da incapacidade (redução de 37,5%) em pacientes que realizaram a DBS, avaliados pela escala Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). é importante destacar a consistência em relação aos resultados sempre mostrarem benefício e a magnitude do efeito, que é relevante clinicamente. Os estudos observacionais incluídos também sugerem resultados positivos com o uso da DBS, com qualidade geral da evidência variando de baixa a muito baixa devido ao risco de viés grave ou crítico, principalmente pela presença de potenciais fatores de confundimento e/ou problemas relacionados ao cegamento (ausência de descrição ou relato inadequado). Para distonia cervical, foram incluídos 13 estudos que envolveram 300 pacientes, a maioria dos estudos incluindo apenas adultos. Entre os estudos identificados um era ECR comparando a DBS com procedimento sham; os demais estudos clínicos eram não randomizados (n=2) ou observacionais (estudos de coorte (n=9) e caso-controle (n=1). O ECR avaliou 62 pacientes adultos e os resultados, avaliados pela escala Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), indicam que a DBS reduz o comprometimento motor (redução média de 5,1 pontos), incapacidade (redução média de 5,6 pontos) e dor (redução média de 4,4 pontos) em pacientes com distonia cervical refratária ao tratamento farmacológico quando comparado com a estimulação simulada. Novamente é importante ressaltar que os resultados foram clinicamente relevantes e observou-se consistência entre os achados no ECR e nos demais estudos. Os estudos observacionais incluídos também relatam resultados positivos com o uso da DBS. AVALIAÇÃO ECONÔMICA: A razão de custo-efetividade incremental da ampliação de uso da DBS foi de R$ 4.378,58 por QALY na distonia generalizada e de R$46.119,11 por QALY na distonia cervical, com a maior parte dos resultados demonstrando superioridade clínica da tecnologia avaliada na análise de sensibilidade. Pela análise de sensibilidade probabilística, 95% dos valores de RCEI estão abaixo de R$7.000 para a distonia generalizada e abaixo de R$1.000.000,00 para a cervical. ANÁLISE DE IMPACTO ORÇAMENTÁRIO: Estima-se que 945 pessoas possuem distonia generalizada e 10.698 distonias cervical no Brasil e que 482 pacientes sejam passíveis de serem tratados com DBS em 2022. Considerando a participação de mercado do procedimento, 72 pacientes fariam a DBS em 2022, 124 em 2023, 131 em 2024, 98 em 2025 e 55 em 2026. Isso corresponde, em uma ampliação de uso progressiva, um impacto orçamentário de, aproximadamente, R$7.710.181,32 em 5 anos. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: No Monitoramento do Horizonte Tecnológico foram encontradas 2 novas tecnologias com registros ANVISA e FDA (Percept PC Brain Sense e Vercise Genus). Em relação aos depósitos e patentes concedidas foi possível evidenciar 1 documento patentário, com depósito em 2021, referente a métodos e sistemas para estimulação cerebral profunda focalizada não invasiva. CONSIDERAÇÕES FINAIS: As evidências disponíveis para a comparação entre DBS e estimulação simulada para os tipos de distonia avaliadas foram baseadas apenas em dois ECRs. Os resultados dos ECRs mostraram resultados favoráveis à intervenção. Os estudos observacionais identificados, ainda que apresentem limitações metodológicas, também apoiam os resultados dos ECRs avaliados. Como o cuidado da distonia em casos refratários ao tratamento usual carece de alternativas terapêuticas é possível que os pacientes com distonia já façam uso desse procedimento por meio dos CIDs do grupo R (R250, R251, R252, R253 e R258), para os quais o procedimento já está disponível no SUS. RECOMENDAÇÃO PRELIMINAR: os membros presentes no Plenário da Conitec, em sua 110ª Reunião Ordinária, realizada no dia 06 de julho de 2022, deliberaram que a matéria fosse disponibilizada em consulta pública com recomendação preliminar favorável à ampliação de uso da estimulação cerebral profunda para o tratamento da distonia. Para essa recomendação, a Conitec considerou que as evidências acerca da eficácia e segurança do procedimento são escassas, mas provém de ensaios clínicos randomizados com resultados clinicamente relevantes, o quadro clínico que exige seu uso seria para aqueles pacientes refratários a todos os demais tratamentos. CONSULTA PÚBLICA: Todos os participantes da CP nº 50/2022, que realizaram contribuições frente ao tema avaliado, realizada entre os dias 01/08/2022 e 22/08/2022, concordaram com recomendação preliminar da Conitec favorável à ampliação de uso da estimulação cerebral profunda para o tratamento da distonia primária generalizada e distonia cervical. Foram recebidas 23 contribuições, sendo 13 através do formulário técnico-científico e 10 através do formulário de experiência ou opinião. De forma geral, as contribuições ressaltaram os benefícios clínicos do procedimento, principalmente destacando melhora da qualidade de vida. Também comentaram a respeito do alto custo e dificuldade de acesso ao procedimento. RECOMENDAÇÃO FINAL DA CONITEC: Pelo exposto, o Plenário da Conitec, em sua 112ª Reunião Ordinária, realizada no dia 31 de agosto de 2022, deliberou por unanimidade recomendar a ampliação de uso da estimulação cerebral profunda para o tratamento da distonia primária generalizada e distonia cervical em pacientes refratários a terapia convencional. Os membros da Conitec consideraram os benefícios proporcionados pelo procedimento e a necessidade de uso para aqueles pacientes refratários aos demais tratamentos. A consulta pública não trouxe elementos para mudança da recomendação preliminar. Por fim, foi assinado o Registro de Deliberação nº 767/2022. DECISÃO: de ampliar o uso, no âmbito do Sistema Único de Saúde - SUS, da estimulação cerebral profunda para o tratamento de distonias, conforme protocolo estabelecido pelo Ministério da Saúde, conforme a Portaria nº 108, publicada no Diário Oficial da União nº 192, seção 1, página 61, em 7 de outubro de 2022.

Trends in safety and cost of deep brain stimulation for treatment of movement disorders in the United States: 2002-2014.

PURPOSE: Deep brain stimulation (DBS) is being increasingly utilized to treat movement disorders including Parkinson's disease (PD), essential tremor (ET), and dystonia. An improved understanding of national trends in safety and cost is necessary. Herein, our objectives are to (1) characterize complication, mortality, and cost profiles of patients undergoing DBS for movement disorders in the United States, (2) identify predictors of morbidity and mortality, and (3) evaluate impact of complications on cost. METHODS: DBS surgeries were extracted from the National Inpatient Sample (NIS) 2002-2014 for the clinical indications of PD, ET, and dystonia. Patient characteristics and eight complication categories (hardware malfunction, infection, neurological, other haemorrhagic, thromboembolic, cardiac, pulmonary, and renal/urinary) were reviewed. Outcomes included complications, mortality, hospitalization length, and inflation-adjusted cost. RESULTS: There were 44,866 weighted admissions (PD-73.5%, ET-22.7%, dystonia-3.8%). The number of procedures increased 2.22-fold from 2002 to 2014 (N = 2372 in 2002; N = 5260 in 2014). Inpatient cost was $22,802 ± 13,164, remaining stable from 2002 to 2014 ($24,188 ± 15,910, $20,630 ± 11,031, respectively). Four percent experienced complications (dystonia-6.0%, PD-4.4%, ET-3.1%, p < .001). In-hospital mortality was 0.2%. Cost was greater in patients with complications ($36,306 ± 29,263 vs. $22,196 ± 11,560, p < .001). Most common complications were renal/urinary (1.5%), neurological (1.1%), and pulmonary (0.7%). Thromboembolic, pulmonary, and haemorrhagic complications were associated with greatest cost. CONCLUSION: Increased DBS utilization for adult movement disorders in the United States from 2002 to 2014 was attributed to rapid adoption by teaching hospitals for PD. DBS remains a safe procedure with low overall complications and stable inpatient costs from 2002 to 2014. Complication risks vary by type of movement disorder, and although rare, multiple complications increase morbidity and cost of care.

American Cancer Society Head and Neck Cancer Survivorship Care Guideline.

Answer questions and earn CME/CNE The American Cancer Society Head and Neck Cancer Survivorship Care Guideline was developed to assist primary care clinicians and other health practitioners with the care of head and neck cancer survivors, including monitoring for recurrence, screening for second primary cancers, assessment and management of long-term and late effects, health promotion, and care coordination. A systematic review of the literature was conducted using PubMed through April 2015, and a multidisciplinary expert workgroup with expertise in primary care, dentistry, surgical oncology, medical oncology, radiation oncology, clinical psychology, speech-language pathology, physical medicine and rehabilitation, the patient perspective, and nursing was assembled. While the guideline is based on a systematic review of the current literature, most evidence is not sufficient to warrant a strong recommendation. Therefore, recommendations should be viewed as consensus-based management strategies for assisting patients with physical and psychosocial effects of head and neck cancer and its treatment. CA Cancer J Clin 2016;66:203-239. © 2016 American Cancer Society.

Internal Pulse Generators in Deep Brain Stimulation: Rechargeable or Not?

OBJECTIVE: Deep brain stimulation (DBS) is a cost-effective strategy for the treatment of different neurologic disorders. However, DBS procedures are associated with high costs of implantation and replacement of the internal pulse generator (IPG). Different manufacturers propose the use of rechargeable IPGs. The objective of this study is to compare the implantation costs of nonrechargeable IPGs versus the estimated costs of rechargeable IPGs in different categories of patients to evaluate if an economic advantage for the health care system could be derived. METHODS: The study looked at 149 patients who underwent a surgical procedure for IPG replacement. In a hypothetical scenario, rechargeable IPGs were implanted instead of nonrechargeable IPGs at the time of DBS system implantation. Another scenario was outlined in a perspective period of time, corresponding to the patients' life expectancy. Costs were calculated, and inferential analysis was performed. RESULTS: A savings of €234,194, including the cost of management of complications, was calculated during a follow-up period of 7.9 years. In a comprehensive life expectancy period of 47 years, a savings of €5,918,188 would be obtained (P < 0.05). Long-term group data point out that a relevant savings would be expected from implantation of rechargeable IPGs in dystonic patients (P < 0.05) and patients with Parkinson disease (P < 0.05), and a savings is projected to occur in other categories of patients (P < 0.05). CONCLUSIONS: Implantation of rechargeable IPGs presents clinical advantages compared with nonrechargeable devices. A huge economic savings can be realized with the implantation of rechargeable IPGs in categories of patients implanted with IPGs for DBS.

[Neuromuscular electric stimulation therapy in otorhinolaryngology]. / Neuromuskuläre Elektrostimulationsverfahren in der HNO-Heilkunde.

BACKGROUND: Animal experiments have shown that after specific nerve traumatization, neuromuscular electrostimulation (NMES) can promote nerve regeneration and reduce synkinesia without negatively interfering with normal regeneration processes. NMES is used routinely in physical rehabilitation medicine. METHODS: This systematic literature search in the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, the DAHTA database, the Health Technology Assessment Database and MEDLINE or PubMed considered studies on the use of NMES in otorhinolaryngology that have been published in German or English. RESULTS: The search identified 180 studies. These were evaluated and relevant studies were included in the further evaluation. DISCUSSION: In the fields of otorhinolaryngology and phoniatry/paediatric audiology, clinical studies investigating the effects of NMES on facial and laryngeal paresis, as well as dysphonia and dysphagia have been carried out. The evidence collected to date is encouraging; particularly for the treatment of certain forms of dysphagia and laryngeal paresis.

Anterocollis and camptocormia in parkinsonism: a current assessment.

Postural deformities in parkinsonian syndromes are well recognized, but poorly understood and largely refractory to available therapies. In recent times a number of hypotheses have been proposed to explain the underlying etiology of anterocollis and camptocormia, but currently there is no consensus. As these conditions are more precisely characterized we begin to uncover that this is a heterogeneous and evolving phenomenon. These conditions bring to light the inadequacies of our current tools to study biomechanics of posture, neuromuscular disorders, and dystonic muscular contractions. The development of objective, accurate tools to directly study and measure the severity of these postural disorders will allow for further understanding of the pathophysiology, the development of novel therapeutics, and adequate clinical trial design.

Incidence and management of venous air embolisms during awake deep brain stimulation surgery in a large clinical series.

BACKGROUND/AIMS: Venous air embolism (VAE) is a potential complication during neurosurgical procedures, particularly in the sitting position. The diagnosis and management of VAE in patients undergoing awake deep brain stimulation (DBS) lead implantation in the sitting position are underreported. METHODS: We performed a retrospective chart review of 467 consecutive DBS surgeries at the University of California, San Francisco. Data was collected for patient demographics, diagnosis, intraoperative events, and postoperative course. RESULTS: Six cases of clinically diagnosed VAE were found, amounting to a total incidence of 1.3% per procedure. We did not observe a statistical association with patient age, diagnosis, or DBS target. The most common symptoms of intraoperative VAE were coughing, oxygen desaturation, and hypotension. In all cases, VAE was treated by copious irrigation of the surgical field and lowering the patient's head. In 4 cases, DBS implantation was abandoned because of ongoing symptoms of VAE. The respiratory outcome in all patients was good after several days of close observation. CONCLUSION: The incidence of VAE during DBS procedures is small, but prompt recognition and management of VAE are critical to avoid further associated complications.

[Is there are needs treating the adolescents with syndrome of vegetative dysfunction?].

Article presents the pathogenesis aspects and clinical data of adolescents with syndrome of vegetative dysfunction. The authors observe the structure of different clinical forms, reflect on conditions and situation, when adolescents needs a stable complex of etiopathogenetic therapy to control autonomic nervous system dysfunction.

The effect of deep brain stimulation on quality of life in movement disorders.

Deep brain stimulation (DBS) is a viable treatment alternative for patients with Parkinson's disease (PD), essential tremor (ET), dystonia, and cerebellar outflow tremors. When poorly controlled, these disorders have detrimental effects on the patient's health related quality of life (HRQoL). Instruments that measure HRQoL are useful tools to assess burden of disease and the impact of therapeutic interventions on activities of daily living, employment, and other functions. We systematically and critically reviewed the literature on the effects of DBS on HRQoL in PD, ET, dystonia, and cerebellar outflow tremor related to multiple sclerosis.

Utilization and perceived effectiveness of complementary and alternative medicine in patients with dystonia.

The use of complementary and alternative medicine (CAM) is increasing worldwide, especially by patients with chronic diseases. To date, no data are available about utilization and perceived effectiveness of CAM in patients with dystonia. A questionnaire survey on utilization and costs of CAM was completed by 180 members of the German Dystonia Society, a patient advocate group. In total, 131 dystonia patients (73%) were current or former users of CAM, 55 patients used CAM in addition to botulinum toxin A injections, and 86 patients had experience with three or more CAM methods. The options used most widely were acupuncture (56%), relaxation techniques (44%), homeopathy (27%), and massages (26%). Among users of specific CAM methods, breathing therapy, Feldenkrais, massages, and relaxation techniques were perceived as most effective. On average, patients spent 1,513 Euro on CAM without reimbursement. There was no correlation between costs and perceived effectiveness of different methods. In line with other studies on chronically ill patients, our results show that dystonia patients frequently utilize CAM methods, often in addition to conventional treatment. There is a growing need to evaluate scientifically the effect of CAM methods on symptom severity and quality of life in dystonia, to prevent utilization of costly and ineffective CAM treatments.

[Living with dystonia. A questionnaire study among members of the Swedish Dystonia Patient Association]. / Att leva med dystoni. En enkätundersökning till Svensk dystoniförenings medlemmar.

The dystonias are movement disorders with sustained muscle contractions causing twisting movements or abnormal postures. A patient survey sent to 268 members of the Swedish Dystonia Patient Association was returned by 221 (82%). Most of the patients (81%) were women and the most common form was cervical dystonia (spasmodic torticollis). Median age at onset was 41.6 years. The time from onset of symptoms to correct diagnosis was on average 6 years. 21% had relatives with movement derangements. Injection with Botulinum toxin and physical therapy were ranked as the most effective treatments. Many patients expressed a need for more physical therapy as well as a desire to meet the same physician each time and to receive more intensive psychological support.