Estimulação cerebral por pulsos sonoros de baixa frequência como coadjuvante nas alterações das funções corticais superiores / Non-invasive brain stimulation by low-frequency sound pulses as an adjunct to changes in higher cortical functions

Não há dúvidas sobre os prejuízos na vida humana, extensivos à família e sociedade como um todo, abrangendo todos os aspectos funcionais das pessoas envolvidas, além do indivíduo, originados dos traumatismos cranioencefálico, agudos e crônicos, externos ou internos: acidentes, atropelamentos, quedas, crimes, acidente vascular cerebral, doenças com neurodegeneração progressiva, resultando em estados demenciais. Ao longo de meio século, houve a introdução contínua de medicamentos, com resultados usualmente contraditórios e frustrantes, exigindo novas tentativas com outras classes farmacológicas. No todo, a limitação se faz sentir na impossibilidade de reversão ou mesmo de mera estabilização dos danos neurológicos, e inocuidade em termos de estimulação da neuroplasticidade. Uma exceção parece ser uma nova abordagem: a estimulação cerebral profunda por pulsos sonoros de baixa frequência (Transcranial Pulse Stimulation, ou TPS). Ainda pouco conhecida, a não ser em alguns centros de tratamento, tem se mostrado ser um acréscimo válido, por complementar os programas multidisciplinares de reabilitação

There is no doubt about the damage to human life, also extended to family and society as a whole, regarding all the functional aspects of those involved, not only the patient itself, which originates from traumatic brain injury, acute or chronic, for external or internal reasons, such as accidents, run overs, falls, crimes, stroke, progressive neurodegenerative diseases that result in dementia states. Over half a century, drugs have been continuously introduced, however their results have constantly been contradictory and frustrating, requiring new attempts with other pharmacological classes. Overall, the limitation is felt in the impossibility of reversing or even merely stabilizing the neurological damage and inefficacy regarding neuroplasticity stimulation. One exception seems to be a new approach, the non-invasive brain stimulation by low-frequency sound pulses (Transcranial Pulse Stimulation, or TPS). Except for some treatment centers, TPS is still unknown, however it has shown to be a valid adjunct in multidisciplinary rehabilitation programs

Exploring clinical outcomes in patients with idiopathic/inherited isolated generalized dystonia and stimulation of the subthalamic region / Explorando os desfechos clínicos em pacientes com distonia idiopática/hereditária generalizada isolada submetidos a estimulação da região subtalâmica

Abstract Background Deep Brain Stimulation (DBS) is an established treatment option for refractory dystonia, but the improvement among the patients is variable. Objective To describe the outcomes of DBS of the subthalamic region (STN) in dystonic patients and to determine whether the volume of tissue activated (VTA) inside the STN or the structural connectivity between the area stimulated and different regions of the brain are associated with dystonia improvement. Methods The response to DBS was measured by the Burke-Fahn-Marsden Dystonia Rating Scale (BFM) before and 7 months after surgery in patients with generalized isolated dystonia of inherited/idiopathic etiology. The sum of the two overlapping STN volumes from both hemispheres was correlated with the change in BFM scores to assess whether the area stimulated inside the STN affects the clinical outcome. Structural connectivity estimates between the VTA (of each patient) and different brain regions were computed using a normative connectome taken from healthy subjects. Results Five patients were included. The baseline BFM motor and disability subscores were 78.30 ± 13.55 (62.00-98.00) and 20.60 ± 7.80 (13.00-32.00), respectively. Patients improved dystonic symptoms, though differently. No relationships were found between the VTA inside the STN and the BFM improvement after surgery (p = 0.463). However, the connectivity between the VTA and the cerebellum structurally correlated with dystonia improvement (p = 0.003). Conclusions These data suggest that the volume of the stimulated STN does not explain the variance in outcomes in dystonia. Still, the connectivity pattern between the region stimulated and the cerebellum is linked to outcomes of patients.

Resumo Antecedentes A estimulação cerebral profunda (ECP) é um tratamento estabelecido para distonias refratárias. Porém, a melhora dos pacientes é variável. Objetivo O objetivo do estudo foi descrever os desfechos da ECP da região do núcleo subtalâmico (NST) e determinar se o volume de tecido ativado (VTA) dentro do NST ou se a conectividade estrutural entre a área estimulada e diferentes regiões cerebrais estão associadas a melhora da distonia. Métodos A resposta da ECP em pacientes com distonia generalizada isolada de etiologia hereditária/idiopática foi mensurada pela escala de Burke-Fahr-Marsden Dystonia Rating Scale (BFM) antes e 7 meses após a cirurgia. A soma dos volumes do NST nos dois hemisférios foi correlacionada com a melhora nos escores do BFM para avaliar se a área estimulada dentro do NST afeta o desfecho clínico. A conectividade estrutural estimada entre o VTA de cada paciente e as diferentes regiões cerebrais foram computadas usando um conectoma normativo retirado de indivíduos saudáveis. Resultados Cinco pacientes com idade de 40,00 ± 7,30 anos foram incluídos. O BFM motor e de incapacidade basal eram de 78,30 ± 13,55 (62,00-98,00) e 20,60 ± 7,80 (13,00-32,00), respectivamente. Os pacientes melhoraram com a cirurgia, mas com variabilidade. Não houve relação entre o VTA dentro do NST e a melhora do BFM após a cirurgia (p = 0.463). Entretanto, a conectividade estrutural entre o VTA e o cerebelo correlacionaram com a melhora da distonia (p = 0.003). Conclusão Os dados sugerem que o VTA dentro do NST não explica a variabilidade do desfecho clínico na distonia. Porém, o padrão de conectividade entre a região estimulada e o cerebelo foi relacionada com o desfecho dos pacientes.

Analyzing the Ethical Challenges of Deep Brain Stimulation Technology for Patients, Doctors, and Researchers / 中国医学伦理学

Deep brain stimulation (DBS) is an invasive treatment that involves implanting electrodes into the brain to electrically stimulate specific brain regions, bringing new hope for the treatment of motor and psychiatric neurological diseases. This technology is closely related to human consciousness and has sparked heated debates on topics such as consciousness autonomy and personality integrity. Starting from the core principles of protecting patients, this paper explored the controversial issues of consciousness autonomy and medical autonomy principles in DBS practice, and discussed the ethical considerations in informed consent, patient inclusion, information collection, and cutting-edge scientific fields from the perspectives of patients, clinicians, and researchers.

Study on deep brain magnetic stimulation method based on magnetic replicator / 生物医学工程学杂志

Existing neuroregulatory techniques can achieve precise stimulation of the whole brain or cortex, but high-focus deep brain stimulation has been a technical bottleneck in this field. In this paper, based on the theory of negative permeability emerged in recent years, a simulation model of magnetic replicator is established to study the distribution of the induced electric field in the deep brain and explore the possibility of deep focusing, which is compared with the traditional magnetic stimulation method. Simulation results show that a single magnetic replicator realized remote magnetic source. Under the condition of the same position and compared with the traditional method of stimulating, the former generated smaller induced electric field which sharply reduced with distance. By superposition of the magnetic field replicator, the induced electric field intensity could be increased and the focus could be improved, reducing the number of peripheral wires while guaranteeing good focus. The magnetic replicator model established in this paper provides a new idea for precise deep brain stimulation, which can be combined with neuroregulatory techniques in the future to lay a foundation for clinical application.

Estimulación cerebral profunda del globo pálido interno en el síndrome de distonía mioclónica: serie de 3 casos y revisión de la literatura / Deep brain stimulation of the internal globus pallidus in myoclonus-dystonia syndrome: a case series and review of the literature

RESUMEN INTRODUCCIÓN: La distonía mioclónica es un trastorno del movimiento con poca prevalencia, pero muy discapacitante, en el cual es frecuente la refractariedad al tratamiento médico. Cómo opción terapéutica se ha planteado la estimulación cerebral profunda, buscando con ello mejorar la función motora, la discapacidad y la calidad de vida de estos pacientes. MATERIALES Y MÉTODOS: Se presentan 3 pacientes con diagnóstico clínico de distonía mioclónica sin confirmación genética, que fueron llevados a estimulación cerebral profunda bilateral del globo pálido interno. RESULTADOS: Se evidenció una mejoría significativa en la evaluación de la escala unificada de mioclonías (80-90 %) y en la escala de distonía de Burke-Fahn-Marsden (tanto en movilidad como en discapacidad). La mejoría clínica se evidenció en los tres pacientes, en periodos de seguimiento que estuvieron entre los 6 meses y los 5 años luego de la estimulación cerebral profunda. DISCUSIÓN Y CONCLUSIONES: Los hallazgos en esta serie de 3 pacientes colombianos son consistentes con lo reportado en la literatura. Sin embargo, aportan información sobre el desenlace de pacientes sin genotipificación sometidos a estimulación cerebral profunda, dado que la eficacia de la intervención en pacientes con distonía sin confirmación genética aún no ha sido determinada, y depende de otros factores como la edad, el tiempo de evolución y el tipo de distonía.

ABSTRACT INTRODUCTION: Myoclonic dystonia is a movement disorder with low prevalence, but very disabling, where refractoriness to medical treatment is frequent. Deep brain stimulation has been proposed as a therapeutic option, seeking to improve motor function, disability and quality of life in these patients. MATERIALS AND METHODS: We present 3 patients with a clinical diagnosis of Myoclonic-Dystonia without genetic confirmation, who underwent bilateral deep brain stimulation of the Globus Pallidus Internus. RESULTS: A significant improvement was evidenced in the evaluation of the unified myoclonus scale (80-90 %) and in the Burke-Fahn-Marsden dystonia scale (both in mobility and in disability). The clinical improvement was evidenced in the 3 patients, in follow-up periods that were between 6 months and 5 years after deep brain stimulation. DISCUSSION AND CONCLUSIONS: Findings in this Colombian case series are consistent with that reported in the literature. However, the current description provides information on the outcome of patients without genotyping undergoing deep brain stimulation, considering that the efficacy of the intervention in these types of patients without genetic confirmation has not been determined and depends on other factors.

Nueva mutación en el gen KMT2B como causa de distonía generalizada de inicio temprano: reporte de caso / Early-onset generalized dystonia caused by a new mutation in the KMT2B gene: Case report

La distonía por mutación en el gen KMT2B es un subtipo recientemente descrito del inicio focal de la enfermedad en los miembros inferiores que, posteriormente, evoluciona a una forma generalizada con compromiso cervical y orofaríngeo, disartria, trastorno secundario de la deglución y discapacidad intelectual. Se describe el caso de una escolar de 10 años de edad, sin antecedentes de consanguinidad ni historia familiar de enfermedad neurológica, que presentó alteración de la marcha y distonía de inicio focal, de curso progresivo a una forma generalizada que afectó sus músculos orofaciales y bulbares con alteración significativa del lenguaje y la deglución. Los estudios metabólicos y sistémicos, incluidas las neuroimágenes, no evidenciaron anormalidades. Se hizo una secuenciación genómica completa y se identificó una nueva variante, probablemente patogénica heterocigota, en el gen KMT2B, la c.1205delC, p.(Pro402Hisfs*5), que causa desplazamiento en el marco de lectura. Este hallazgo explica el fenotipo de la paciente y la distonía de inicio temprano autosómica dominante. Se reporta una nueva mutación heterocigota del gen KMT2B como causa de distonía generalizada de inicio temprano, no reportada en la literatura especializada hasta el momento. El diagnóstico de esta afección tiene implicaciones en el tratamiento y el pronóstico de los pacientes, porque las estrategias terapéuticas tempranas pueden prevenir su rápido deterioro y un curso más grave de la enfermedad.

Introduction: KMT2B-related dystonia is a recently described subtype of focal-onset dystonia in the lower limbs, evolving into a generalized form with cervical, oropharyngeal involvement, dysarthria, swallowing disorder and intellectual disability. Clinical case: We describe the case of a 10-year-old female patient, without a history of consanguinity or neurological disease. She manifested abnormal gait and dystonia with focal onset and progressive course with evolution into generalized dystonia, affecting orofacial and bulbar muscles, significant alteration of language and swallowing. Metabolic and systemic studies, including neuroimaging, were found to be normal. A complete genomic sequencing study was performed identifying a new, probably pathogenic, heterozygous variant in the KMT2B gene, c.1205delC, p. (Pro402Hisfs*5), causing displacement in the reading frame, a finding that explains the patient's phenotype and it is associated to autosomal dominant childhood-onset dystonia-28. Conclusion: We report a new heterozygous mutation in the KMT2B gene as a cause of generalized early-onset dystonia not reported in the literature until the date. The diagnosis of this pathology has implications for the treatment and prognosis of patients, given that therapeutic strategies implemented early can prevent the fast deterioration and severe course of this disease.

Comparación del rendimiento de pruebas cognitivas en pacientes con Enfermedad de Parkinson con y sin estimulación cerebral profunda / Comparison of the performance of cognitive tests in Parkinson Disease patients with and without Deep Brain Stimulation

Resumen Los pacientes diagnosticados con Enfermedad de Parkinson (EP) presentan alteraciones motoras concomitantes a otras alteraciones de tipo cognitivo, conductual o emocional. Una de las alternativas al tratamiento farmacológico es la estimulación cerebral profunda (ECP). Existen reportes de alteraciones en el rendimiento de tareas cognitivas tras procedimiento de ECP, lo que podría sugerir que el procedimiento es responsable de estos cambios cognitivos. El objetivo del estudio fue comparar los resultados del rendimiento en pruebas cognitivas de pacientes con EP de dos grupos (con ECP y sin ECP). Se recolectaron los resultados de 47 pacientes (n = 16 ECP; n = 31 sin ECP) durante los años de 2011 hasta 2015. Dentro de las funciones y variables evaluadas se encuentran: categorización visual, flexibilidad cognitiva, solución de problemas, atención selectiva, velocidad de procesamiento, inhibición conductual y calidad de vida. En general, no se encontraron diferencias significativas entre los grupos en las funciones evaluadas. En el grupo de participantes con ECP, se encontró mayor cantidad de correlaciones entre las pruebas de semejanzas y las de dígitos inversos, listas de palabras, búsqueda de símbolos y las subpruebas del Wisconsin Card Sorting Test. Así mismo, en los pacientes con ECP se presentó una percepción menor de calidad de vida asociada al tiempo de la enfermedad en comparación con el grupo sin ECP. En conclusión, estos resultados son congruentes con estudios similares de evaluación neuropsicológica y se discute el papel del tratamiento de estimulación en los pacientes, los cuales no siempre tienen un impacto positivo sobre la calidad de vida percibida.

Abstract Patients diagnosed with Parkinson's disease show motor alterations together to cognitive, behavioral, and emotional disturbances. An alternative treatment to the exclusive pharmacological medication is the Deep Brain Stimulation procedure (DBS). Some studies have shown altered behavioral patterns after DBS device implantation, suggesting a relationship between a particular performance in cognitive tests derived from the DBS procedure. Our study aimed to compare the performance of cognitive tests in Parkinson's disease patients with and without DBS. Results were analyzed from 47 patients (n = 16 DBS; n = 31 without DBS) in a range since 2011 to 2015. Functions tested were visual categorization, cognitive flexibility, problem solutions, selective attention, cognitive processing speed, behavioral inhibition, and quality of life. In general, there are non-significative differences between groups in functions tested. However, correlations were found depending on the group (DBS or without DBS patients), with more positive correlations inside the DBS group between the similarity test and inversed digits, list of words, symbol search and the sub-test of the Wisconsin Card Sorting Test. In addition, the DBS group showed a low perception of the quality of life associated with the disorder´s time compared to the without DBS group. In conclusion, these results are congruent with similar studies of neuropsychological evaluation, and the role of treatment is discussed below the perception of the quality of life.

A narrative review on invasive brain stimulation for treatment-resistant depression

While most patients with depression respond to pharmacotherapy and psychotherapy, about one-third will present treatment resistance to these interventions. For patients with treatment-resistant depression (TRD), invasive neurostimulation therapies such as vagus nerve stimulation, deep brain stimulation, and epidural cortical stimulation may be considered. We performed a narrative review of the published literature to identify papers discussing clinical studies with invasive neurostimulation therapies for TRD. After a database search and title and abstract screening, relevant English-language articles were analyzed. Vagus nerve stimulation, approved by the U.S. Food and Drug Administration as a TRD treatment, may take several months to show therapeutic benefits, and the average response rate varies from 15.2-83%. Deep brain stimulation studies have shown encouraging results, including rapid response rates (> 30%), despite conflicting findings from randomized controlled trials. Several brain regions, such as the subcallosal-cingulate gyrus, nucleus accumbens, ventral capsule/ventral striatum, anterior limb of the internal capsule, medial-forebrain bundle, lateral habenula, inferior-thalamic peduncle, and the bed-nucleus of the stria terminalis have been identified as key targets for TRD management. Epidural cortical stimulation, an invasive intervention with few reported cases, showed positive results (40-60% response), although more extensive trials are needed to confirm its potential in patients with TRD.

Abordaje perioperatorio en cirugía neurológica con el paciente despierto / Perioperative approach in neurological surgery with the patient awake

Resumen: La craneotomía con el paciente despierto se refiere a aquellos procedimientos en los que el paciente conserva su estado de consciencia durante toda la cirugía o en parte de ésta con el objetivo de explorar la integridad de sus funciones cerebrales superiores en tiempo real. Estas técnicas neuroanestésicas son útiles para ayudar al neurocirujano a preservar la integridad del tejido cerebral, o bien, no causar mayor daño del que la propia enfermedad ha causado.

Abstract: Awake craniotomy refers to those procedures in which the patient remains conscious for all or part the time, with the aim of explore in real time the integrity of their higher brain functions. This kind of neuroanesthetic techniques are useful in assisting the neurosurgeon to preserve the integrity of the brain or not to damage more than what the disease has caused.

Deep brain stimulation in Parkinson's disease: state of the art and future perspectives / Estimulação cerebral profunda na doença de Parkinson: estado da arte e perspectivas futuras

ABSTRACT For more than 30 years, Deep Brain Stimulation (DBS) has been a therapeutic option for Parkinson's disease (PD) treatment. However, this therapy is still underutilized mainly due to misinformation regarding risks and clinical outcomes. DBS can ameliorate several motor and non-motor symptoms, improving patients' quality of life. Furthermore, most of the improvement after DBS is long-lasting and present even in advanced PD. Adequate patient selection, precise electric leads placement, and correct DBS programming are paramount for good surgical outcomes. Nonetheless, DBS still has many limitations: axial symptoms and signs, such as speech, balance and gait, do not improve to the same extent as appendicular symptoms and can even be worsened as a direct or indirect consequence of surgery and stimulation. In addition, there are still unanswered questions regarding patient's selection, surgical planning and programming techniques, such as the role of surgicogenomics, more precise imaging-based lead placement, new brain targets, advanced programming strategies and hardware features. The net effect of these innovations should not only be to refine the beneficial effect we currently observe on selected symptoms and signs but also to improve treatment resistant facets of PD, such as axial and non-motor features. In this review, we discuss the current state of the art regarding DBS selection, implant, and programming, and explore new advances in the DBS field.

RESUMO Há mais de 30 anos, a Estimulação Cerebral Profunda (ECP) é uma opção de tratamento para pessoas com doença de Parkinson (DP). Apesar disso, a ECP ainda é subutilizada, em grande parte por desinformação acerca dos riscos e dos benefícios desse tratamento. A ECP melhora os sintomas motores e não motores da DP, melhorando, assim, a qualidade de vida dos pacientes. Grande parte dos benefícios gerados pela ECP têm longa duração, estando presentes até mesmo em fases avançadas da doença. A seleção adequada dos pacientes, o preciso posicionamento dos eletrodos cerebrais, e a programação correta da ECP são fundamentais para que haja benefício após a cirurgia. Todavia, existem ainda muitas limitações em relação ao tratamento com ECP. Sintomas axiais, como fala e marcha, não melhoram tanto quanto os sintomas apendiculares, e podem até mesmo piorar após a cirurgia. Existem muitas dúvidas relacionadas à seleção de pacientes, especialmente nos aspectos de imagem e genética. Em relação à questão cirúrgica, novas técnicas de imagem podem auxiliar o posicionamento correto dos eletrodos cerebrais. Novas estratégias de programação e avanços de hardware podem melhorar desfechos que ainda são limitados. A fim de melhorar sintomas resistentes à ECP, como cognição e marcha, novos alvos cerebrais estão sendo explorados. Na presente revisão, discutimos o atual estado da arte relacionado à ECP, abordando seleção de pacientes, implante cirúrgico de eletrodos, e programação do dispositivo, além de explorarmos novos avanços em desenvolvimento.

Quality of life of patients with Parkinson's disease: a comparison between preoperative and postoperative states among those who were treated with deep brain stimulation / Qualidade de vida de pacientes com doença de Parkinson: uma comparação dos estados pré-operatório e pós-operatório daqueles tratados com estimulação cerebral profunda

ABSTRACT Background: Deep brain stimulation (DBS) is a well-established procedure for treating Parkinson's disease (PD). Although its mechanisms of action are still unclear, improvements in motor symptoms and reductions in medication side effects can be achieved for a significant proportion of patients, with consequent enhancement of quality of life. Objective: To investigate the impact of DBS on the quality of life of PD patients. Methods: This was a retrospective longitudinal study with collection of historical data in a neurosurgery center, from June 2019 to December 2020. The sample was obtained according to convenience, and the Parkinson's Disease Questionnaire (PDQ-39), Unified Parkinson's Disease Rating Scale (UPDRS) III and IV, Trail-Making Test and Verbal Fluency Test were used. Results: Data were collected from 17 patients (13 with subthalamic nucleus DBS and 4 with globus pallidus pars interna DBS). Significant improvement (p=0.008) on the UPDRS III was observed in comparing the preoperative without DBS with the postoperative with DBS. About 47.0% of the patients showed post-surgical improvement in QoL (p=0.29). Thirteen patients were able to complete part A of the Trail-Making Test and four of these also completed part B. Almost 60% of the patients scored sufficiently on the semantic test, whereas only 11.8% scored sufficiently on the orthographic evaluation. No association between implant site and test performance could be traced. Conclusions: Improvements in quality of life and motor function were observed in the majority of the patients enrolled. Despite the limitations of this study, DBS strongly benefits a significant proportion of PD patients when well indicated.

RESUMO Antecedentes: A estimulação cerebral profunda (ECP) é um procedimento bem estabelecido para o tratamento da doença de Parkinson (DP). Embora seus mecanismos de ação não sejam claros, a melhora dos sintomas motores e a redução dos efeitos colaterais dos medicamentos são contempladas em uma proporção significativa de pacientes, com melhora da qualidade de vida. Objetivo: Investigar o impacto da ECP na qualidade de vida de pacientes em DP. Métodos: Trata-se de um estudo longitudinal retrospectivo, com coleta de dados históricos em um centro de neurocirurgia, de junho de 2019 a dezembro de 2020. A amostra foi feita por conveniência, e os questionários Parkinson's Disease Questionnare (PDQ-39), Unified Parkinson's Disease Rating Scale (UPDRS) III e IV, Trail Making Test e Teste de Fluência Verbal foram utilizados. Resultados: Dos dados coletados de 17 pacientes (13 ECP em núcleo subtalâmico e ECP em globo pálido interno) notou-se melhora significativa (p=0,008) no UPDRS III ao se comparar o pré-operatório sem ECP com pós-operatório com ECP, e cerca de 47,0% deles apresentaram melhora pós-cirúrgica na qualidade de vida (p=0,29). Treze pacientes conseguiram completar a parte A do Trail Making Test e quatro também completaram a parte B. Quase 60,0% dos pacientes obtiveram pontuação suficiente no teste semântico, enquanto apenas 11,8% obtiveram pontuação suficiente na avaliação ortográfica. Não foi possível rastrear a associação entre local do implante e desempenho. Conclusões: Melhora na qualidade de vida e na função motora foi observada na maioria dos pacientes. Apesar das limitações do estudo, a ECP beneficia fortemente uma proporção significativa de pacientes em DP quando bem indicada.

Guidelines for Parkinson's disease treatment: consensus from the Movement Disorders Scientific Department of the Brazilian Academy of Neurology - motor symptoms / Diretrizes para o tratamento da doença de Parkinson: consenso do Departamento Científico de Transtornos do Movimento da Academia Brasileira de Neurologia - sintomas motores

ABSTRACT 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.

Resumo O tratamento da doença de Parkinson (DP) constitui um desafio, especialmente por ser considerado muito individualizado. A Academia Brasileira de Neurologia (ABN) identificou a necessidade de disseminar o conhecimento sobre o manejo do tratamento da DP, adaptando as melhores evidências à realidade brasileira. Assim, foi realizada uma revisão sobre as principais orientações de tratamento publicadas, baseada nas recomendações elaboradas por um grupo de especialistas em transtornos do movimento do departamento científico da ABN.

Phenotype and genotype features of 11 children with dystonia 28 caused by KMT2B variants / 中华实用儿科临床杂志

Objective:To summarize the clinical characteristics of children with dystonia 28 (DYT28) caused by KMT2B gene variations so as to improve clinicians′ understanding of the disease. Methods:The clinical manifestations, treatment and gene variation data of 11 children with DYT28 caused by KMT2B gene variations were retrospectively collected and analyzed.The subjects were recruited from the Department of Neurology, Beijing Children′s Hospital, Capital Medical University from March 2018 to January 2021.The patients were followed up. Results:There were 8 males and 3 females.The age at onset was ranging from 1 month to 6 years without inducement.Eight cases were gene-ralized dystonia and 3 cases were multifocal dystonia.The initial symptoms of 7 cases were unilateral or bilateral lower limbs tiptoeing.Four cases presented dysarthria, retching or swallowing difficulties at onset.As the disease progressed, all the cases had laryngeal dystonia, 10 cases had lower limbs dystonia, and 8 cases had upper limbs dystonia.Six cases were complicated with other dyskinesia symptoms.Ten cases had varying degrees of short stature, microcephalus, micrognathia, musculoskeletal abnormalities, intellectual disability, endocrinopathies and sleep difficulties.The brain magnetic resonance imaging showed abnormal in only 1 case.Eleven KMT2B gene pathogenic variants were found, including 8 frameshift variants, 1 in-frame variant and 2 missense variants.Four variants were novel.Eleven cases were followed up at the age of 1 year and 7 months to 17 years and 9 months.One case wasn′t given therapy.The dystonia in 3 cases was mildly improved after medication.Dysfunction of urination and defecation was disappeared in 1 case after medication.The symptom of 6 cases had no improvement after drug therapy.Among the above 6 cases, 5 drug refractory cases had deep brain stimulation, and their dystonia symptoms are all obviously improved; 2 cases had normal control of urination and defecation after deep brain stimulation.The motor scores in the Burke-Fahn-Marsden dystonia rating scale were improved by 55.8%-90.7%, and the disability scores were improved by 14.8%-69.6%. Conclusions:DYT28 caused by KMT2B gene variations is one of the most common and early-onset genetic dystonia in children.The dystonia symptom progresses from local parts to the whole body, prominently involving laryngeal muscles and lower limbs.Control of urination and defecation requires attention.Patients with mild dystonia symptoms can be effectively treated by drugs.However, patients with severe dystonia symptoms were drug refractory, and their dystonia symptoms can be effectively improved by deep brain stimulation.

Lead-DBS: an additional tool for stereotactic surgery

SUMMARY OBJECTIVE: Use Lead-DBS software to analyze stereotactical surgical outcome of an operated population and demonstrate that small target deviations do not compromise the stimulation of desired structures, even with small amperages. METHODS: Image exams of patients submitted to deep brain stimulation for movement disorders treatment were processed in Lead-DBS software. Electrode stereotactic coordinates were subtracted from the planned target and those deviations, compared among different anatomical targets and sides operated firstly and secondly. We also quantified the frequency of relation between the activated tissue volume and the planned target through computer simulations. RESULTS: None of the 16 electrodes were exactly implanted at the planned coordinates. A stimulation of 3 mA reached 62.5% of the times the planned coordinates, rising to 68.75% with a 3,5 mA. No statistical significance was demonstrated in any comparison of laterality and anatomical sites. CONCLUSIONS: The simulation of small amperage fields could reach the intended target even when electrode placement is suboptimal. Furthermore, such a goal can be achieved without overlapping the volume of activated tissue with undesired structures. Software Lead-DBS proved to be a valuable complementary asset for surgical stereotactical result assessment.

Pay attention to the application of neuromodulation therapy in Parkinson′s disease / 中华神经科杂志

There are specific pathological changes in neural circuits and neural network of Parkinson′s disease patients. Neuromodulation therapy can realize the precise treatment of Parkinson′s disease with crucial targets in neural circuits. It is divided into invasive and non-invasive brain stimulation. Invasive brain stimulation mainly refers to deep brain stimulation. The selection of operation time, targets and programming parameters is significant to improve the therapeutic effect of it. Non-invasive brain stimulation mainly includes transcranial magnetic stimulation and transcranial electrical stimulation, which has advantages of safety and strong operability. Comparing to the drug therapy aiming to supply neurotransmitters, neuromodulation therapy has some advantages, and has become a vital option in the precision treatment strategy of Parkinson′s disease.

Clinical strategy for the diagnosis and treatment of dystonia / 中华神经科杂志

Dystonia is a highly heterogeneous disorder both in clinical and genetical manifestation. It is sometimes associated with poor outcomes in clinical practice. Understanding of the definition, classification, mechanism of dystonia is helpful for optimizing management and improving the implementation. Genetic testing for dystonia is important as an accurate molecular diagnosis in certain genes which can influence therapeutic decisions. Referring to the current situation of clinical practice and expert views in China, this article shares the principles of clinical diagnosis and treatment and the application of gene testing, hoping to provide reference to the diagnosis and treatment decisions of dystonia for the ordinary neurologists in the process of medical practice.

Clinical study of deep brain stimulation in the treatment of Parkinson′s disease / 中国医师杂志

Objective:To investigate the clinical effect of deep brain stimulation (DBS) in the treatment of Parkinson′s disease (PD).Methods:32 PD patients treated in Hunan Brain Hospital from January 2016 to December 2018 were selected for the study. Guided by MRI and supplemented by electrophysiological stimulation to correct the target, PD patients were treated with DBS for the nucleus accumbens. Based on Webster and Unified Parkinsons Disease Rating Scale (UPDRS) scores before and after DBS treatment, the clinical treatment effects were evaluated. And the content of Aβ1-42, interleukin (IL)-1β, IL-6, uric acid (UA), malondialdehyde (MDA), homocysteine (Hcy), S-nitrosylated dynamin-relatedprotein 1 (SNO-Drp1) and Drp1 was measured before and after DBS treatment. The ratio of SNO-Drp1/Drp1 was also measured.Results:The Webster score and UPDRS score of PD patients after DBS treatment were lower than those before DBS treatment ( P<0.05). The Aβ1-42 and Drp1content of PD patients after DBS treatment was higher than that before DBS treatment ( P<0.05), while the content of IL-1β, UA, MDA, Hcy and the ratio of SNO-Drp1/Drp1 were lower than before treatment ( P<0.05). Conclusions:DBS has confirmed a good clinical effect in the treatment of PD patients and significantly improved the quality of life of patients.

Role of the Anterior Cingulate Cortex in Translational Pain Research / 神经科学通报·英文版

As the most common symptomatic reason to seek medical consultation, pain is a complex experience that has been classified into different categories and stages. In pain processing, noxious stimuli may activate the anterior cingulate cortex (ACC). But the function of ACC in the different pain conditions is not well discussed. In this review, we elaborate the commonalities and differences from accumulated evidence by a variety of pain assays for physiological pain and pathological pain including inflammatory pain, neuropathic pain, and cancer pain in the ACC, and discuss the cellular receptors and signaling molecules from animal studies. We further summarize the ACC as a new central neuromodulation target for invasive and non-invasive stimulation techniques in clinical pain management. The comprehensive understanding of pain processing in the ACC may lead to bridging the gap in translational research between basic and clinical studies and to develop new therapies.

Neuromodulation-Based Stem Cell Therapy in Brain Repair: Recent Advances and Future Perspectives / 神经科学通报·英文版

Stem cell transplantation holds a promising future for central nervous system repair. Current challenges, however, include spatially and temporally defined cell differentiation and maturation, plus the integration of transplanted neural cells into host circuits. Here we discuss the potential advantages of neuromodulation-based stem cell therapy, which can improve the viability and proliferation of stem cells, guide migration to the repair site, orchestrate the differentiation process, and promote the integration of neural circuitry for functional rehabilitation. All these advantages of neuromodulation make it one potentially valuable tool for further improving the efficiency of stem cell transplantation.

Research progress in the treatment of treatment-resistant depression by deep brain stimulation / 四川精神卫生

In recent years， plenty of studies have demonstrated that deep brain stimulation （DBS） has potential efficacy for treatment-resistant depression. This paper reviews the worldwide research progress of DBS in the treatment of treatment-resistant depression， in which the DBS treatment mechanism， targets and outcomes are discussed， the limitations of current DBS treatment are summarized， and the development direction of DBS is also forecasted， therefore providing a factual basis for relevant experiments in China.