Cirugía ablativa del núcleo subtalámico en la Enfermedad de Parkinson. Consideraciones necesarias / Ablative subthalamic nucleus surgery in Parkinson's disease. Necessary considerations

RESUMEN La enfermedad de Parkinson según la Organización Mundial de Salud, en el año 2016, afectó una persona por cada 100 mayores de 60 años, siendo en cifras absolutas 6,3 millones de personas, y para el año 2030 serán aproximadamente 12 millones de personas en todo el mundo con dicha patología. Este desorden neurodegenerativo, caracterizado por la degradación nigro-estriatal y potenciación de la vía indirecta del circuito motor de los Ganglios Basales sumado al acúmulo de Cuerpos de Lewy en diversas estructuras del Sistema Nervioso Central, afecta progresiva e inevitablemente la calidad de vida de los pacientes, los procederes ablativos del núcleo subtalámico constituyen una alternativa que propicia efecto y seguridad probada en el control de los síntomas de esta enfermedad. Por lo cual se decide describir la ablación del Núcleo subtalámico como tratamiento de la Enfermedad de Parkinson avanzada (AU).

Summary According to the World Health Organization, in 2016 Parkinson's disease affected one person per every 100 people elder 60 years, meaning 6.3 millions of people, and by 2030 it will be around 12 million persons across the world. This neurodegenerative disorder, characterized by the nigro-striatal degradation and potentiation of the indirect route of the basal ganglia motor circuit, added to the accumulation of Lewy bodies in several structures of the Central Nervous System, progressively and inevitably affects the life quality of patients. The ablative procedures of the subthalamic nucleus are an alternative that propitiates proven effect and safety in the control of this disease symptoms. Therefore, the authors decided to describe the subthalamic nucleus ablation as a treatment for advanced Parkinson's disease (AU).

Efeito da técnica de sobrearticulação na voz e na fala em indivíduos com doença de Parkinson após cirurgia de estimulação cerebral profunda / Effect of overarticulation technique in voice and speech of individuals with Parkinson's disease with deep brain stimulation

RESUMO Objetivo Verificar o efeito imediato e após 15 minutos da técnica de sobrearticulação de fala em indivíduos com doença de Parkinson, submetidos à estimulação cerebral profunda em núcleo subtalâmico, nos parâmetros de voz, fala e mímica facial. Métodos Participaram 29 sujeitos com diagnóstico médico de doença de Parkinson, sob tratamento medicamentoso e submetidos à estimulação cerebral profunda em núcleo subtalâmico, com e sem reabilitação fonoaudiológica prévia. Realizou-se gravação em áudio e vídeo de amostra de fala e voz em três momentos: pré-intervenção, pós-imediato e após 15 minutos da realização individual de cinco minutos de uma sequência de exercícios de sobrearticulação de fala. As gravações foram submetidas à avaliação perceptivo-auditiva da voz e perceptivo-visual da mímica facial. Resultados A técnica produziu resultados positivos em 69% dos casos, após 15 minutos de aplicação, em relação aos demais momentos. O parâmetro que mais contribuiu para a identificação da melhor emissão na avaliação perceptivo-auditiva foi articulação (69%), significativamente maior que os demais parâmetros, exceto velocidade de fala. A análise perceptivo-visual mostrou melhora em 58,6% dos casos após 15 minutos, também significativamente melhor que os demais momentos. O parâmetro em que se observou maior proporção de melhora foi na movimentação de boca, sobrancelhas e olhos. Conclusão A técnica de sobrearticulação de fala produz efeito positivo imediato nos aspectos vocais e uma maior expressividade facial, principalmente após 15 minutos de realização.

ABSTRACT Purpose To verify the immediate and after 15 minutes effect of the overarticulation technique in individuals with Parkinson's disease, submitted to deep brain stimulation in subthalamic nucleus, in the voice, speech and facial movements. Methods This study counted with 29 patients with the diagnosis of Parkinson Disease who were undergoing pharmacotherapy and were submitted to deep brain stimulation in the subthalamic nucleus, with and without prior speech therapy. Speech and voice samples were recorded in an audio and video file at three different moments: pre-intervention, immediate post intervention and 15 minutes post intervention. The intervention was the individual performance of 5 minutes exercise consisting of sequence of overarticulation techniques. The audio and video recordings were submitted to the perceptual-judgement of the voice quality and facial movements. Results The technique produced positive results in 69% of the cases after 15 minutes of its application when compared to the other moments. Articulation was the parameter that most contributed in the perceptual-judgment of the best voice quality (69%); it was significantly higher than the other parameters, except speech rate. After 15 minutes of the technique, 58.6% of the patients had improvement in the facial movements, according to the perceptual-judgment which was also significantly better when compared to other moments. The parameter with greater provement was movement of the mouth, eyebrows and eyes. Conclusion The overarticulation technique produces an immediate positive effect on vocal aspects and greater facial expressiveness, especially after 15 minutes.

Estimulación cerebral profunda en enfermedad de Parkinson / Deep brain stimulation in Parkinson's disease

Background: Deep brain stimulation is an essential therapeutic tool in Parkinson's disease. Aim: To assess the results of a series of patients with Parkinson's disease treated with micro-electrode guided subthalamic nucleus stimulation. Material and Methods: Twenty patients with idiopathic Parkinson's disease were studied (10 males). Three months after surgery, we analyzed the change in motor disturbances, medication need to control symptoms and quality of life. Results: We observed a significant improvement in all the assessed variables. Motor involvement determined as OFF hours and expressed as percentage of the day changed from 30 ± 15 to 10 ± 7% in the preoperative and postoperative periods, respectively. ON hours without dyskinesia changed from 17 ± 16 to 78 ± 21%. ON hours with dyskinesia changed from 53 ± 23 to 12 ± 15%. Medication need changed from 1,505 ± 499 to 1,214 ± 528 levodopa equivalents. Parkinson's Disease Questionnaire 39 score changed from 62.9 ± 22.7 to 34.3 ± 18.5. During the 5-year follow-up a continuous improvement of symptoms was observed. Conclusions: Micro-electrode guided subthalamic nucleus functional surgery in patients with Parkinson's disease has good immediate and late results.

Impacto da estimulação cerebral profunda na qualidade de vida e humor em pacientes com doença de Parkinson / Impact of deep brain stimulation on quality of life and mood in patients with Parkinson's disease

A doença de Parkinson (DP) é uma doença neurodegenerativa deri¬vada de uma redução da produção de dopamina. O seu tratamento é basicamente por medidas farmacológicas. No entanto, nos está¬dios avançados da doença, especialmente devido às flutuações do motor, o tratamento farmacológico por si só não é completamente bem-sucedido. Assim, surge a possibilidade de benefícios ao pacien¬te pela técnica de estimulação cerebral profunda (DBS). O objetivo deste estudo foi analisar o impacto do DBS palidal ou subtalâmica sobre a qualidade de vida desses pacientes (QoL). Para tanto, em¬pregaram-se duas escalas, comparando os resultados pré e pós-ope¬ratórios: o Inventário de Depressão de Beck - BDI (avalia o aspecto emocional dos pacientes) e o PDQ-39 (avalia os aspectos motores e as relações sociais). Podemos observar que a avaliação do BDI apon¬tou para uma melhora média de 9,5% e os escores do PDQ-39 me¬lhoraram 10,28%. Há evidências que pacientes submetidos à técnica de DBS subalâmicos ou paliativos mostraram uma QoL de melhoria importante, assim, o DBS surge como um adjuvante na luta contra a doença de Parkinson. (AU)

Parkinson's disease (PD) is a neurodegenerative disorder derived from a reduction of dopamine production. The treatment of PD is basically by pharmacological measures. However, in the advanced stages of the disease, especially due to motor fluctuations, phar¬macological treatment by itself is not completely successful. At that moment, the possibility of the patient´s benefits by the technique of deep brain stimulation (DBS) comes up. The aim of this study was to analyze the impact of pallidal or subthalamic DBS on PD patients' quality of life (QoL). To do so, two scales were employed, comparing the pre and post-operative results: Beck Depression Inventory - BDI (evaluates the patients' emotional aspect) and PDQ-39 (evaluates mo¬tor aspects and social relations). We could observe that BDI evalua¬tion pointed to an average improvement of 9.5% and PDQ-39 scores improved 10.28%. We can conclude that patients who have undergo¬ne the technique of subthalamic or pallidal DBS showed an important improvement QoL. DBS comes up as an adjuvant in the fight against Parkinson's disease. (AU)

The advances of Deep Brain Stimulation (DBS) for treatment of Parkinson's disease (PD)

Advanced Parkinson's disease (PD) is characterized by the presence of motor fluctuations, various degrees of dyskinesia, and disability with functional impact on daily living and independence. Therapeutic management aims to extend levodopa (L-DOPA) benefit while minimizing motor complications and includes, in selected cases, the implementation of drug infusion and surgical techniques. The concept of deep brain stimulation (DBS) for PD was introduced over 20 years ago, but our understanding of the nuances of this procedure continues to improve. This review aims to demonstrate the advances of DBS in the treatment of PD patients. (AU)

Aspectos de comunicação oral em pacientes com doença de Parkinson submetidos à Estimulação Cerebral Profunda / Aspects of oral communication in patients with Parkinson's disease submitted to Deep Brain Stimulation

RESUMO Introdução A Estimulação Cerebral Profunda tem sido considerada uma intervenção satisfatória para os sintomas motores cardinais da doença de Parkinson, porém ainda há poucas evidências sobre seu impacto na comunicação. Objetivo Esse trabalho teve como objetivo caracterizar os seguintes aspectos da comunicação: cognição, linguagem, fala, voz, e autopercepção de dois pacientes com doença de Parkinson em situação pré e pós a cirurgia de implantação da Estimulação Cerebral Profunda. Método Os pacientes foram avaliados através de: um teste de rastreio cognitivo; uma avaliação breve da linguagem; um protocolo autodeclarado e aspectos da voz e da fala, que foram avaliados por um fonoaudiólogoexpertna área e cegado para o estudo. Resultado Observou-se no momento pré-cirurgia que o Caso I apresentava comprometimento nos aspectos cognitivo, da linguagem e voz, enquanto que o Caso II apresentava alteração apenas na voz. A avaliação pós-cirúrgica dos casos mostrou um padrão oposto de efeito da Estimulação Cerebral Profunda, quando analisados os dados pós-cirúrgicos, referente à comunicação. O Caso I, que era considerado com o maior prejuízo no período anterior à cirurgia, apresentou melhora em alguns aspectos, enquanto o Caso II, que era observado com menos prejuízo comunicativo previamente à cirurgia, apresentou piora em outros aspectos. Conclusão Este estudo demonstrou que a Estimulação Cerebral Profunda pode influenciar diferentes aspectos da comunicação, tanto de modo positivo quanto negativo, e que é necessário investigar fatores associados aos diferentes efeitos causados pela Estimulação Cerebral Profunda sobre a comunicação dos pacientes com doença de Parkinson.

ABSTRACT Introduction Deep Brain Stimulation (DBS) has been satisfactorily used to control the cardinal motor symptoms of Parkinson’s disease (PD), but little is known about its impact on communication. Purpose This study aimed to characterize the aspects of cognition, language, speech, voice, and self-perception in two patients with PD, pre- and post- DBS implant surgery. Methods The patients were assessed using a cognitive screening test, a brief language evaluation, a self-declared protocol, and an analysis of the aspects of voice and speech, which was conducted by a specialized Speech-language Therapist who was blinded for the study. Results At the pre-surgery assessment, Case I showed impairment regarding the aspects of cognition, language and voice, whereas Case II showed impairment only with respect to the voice aspect. The post-surgery evaluation of the cases showed an opposite pattern of the effect of DBS after analysis of the communication data: Case I, who presented greater impairment before the surgery, showed improvement in some aspects; Case II, who presented lower communicative impairment before the surgery, showed worsening in other aspects. Conclusion This study shows that DBS may influence different communication aspects both positively and negatively. Factors associated with the different effects caused by DBS on the communication of patients with PD need to be further investigated.

El núcleo subtalámico en la fisiopatología de la enfermedad de Parkinson y su rol como diana quirúrgica / The subthalamic nucleus in the pathophysiology of Parkinson's disease and its role as a surgical target

Parkinson's disease is one of the most common causes of neurological disability, it caused by selective loss of neurons at the substantia nigra, which causes an imbalance in the functioning of the basal ganglia. In the pathophysiological events underlying this disease, hyperactivity of the subthalamic nucleus is more often associated with major clinical manifestations; this structure also plays a fundamental role in motor control, making it an excellent surgical target.

La enfermedad de Parkinson es una de las causas más frecuentes de discapacidad neurológica, se produce por la pérdida selectiva de neuronas a nivel de la sustancia nigra, lo que genera un desbalance en el funcionamiento de los ganglios basales. De los eventos fisiopatológicos subyacentes en esta enfermedad, la hiperactividad del núcleo Subtalámico es el que más se relaciona con las principales manifestaciones clínicas, además esta estructura juega un papel fundamental en el control motor, lo que la convierte en una excelente diana quirúrgica.

Frameless stereotactic for deep brain stimulation placement: operative technique.

Deep brain stimulation (DBS) has been shown to be a safe and effective method for the treatment of refractory Parkinson's disease and other movement disorders. Traditionally, frame-based stereotactic have been the standard technique commonly used for DBS surgery. With the development of image-guided neurosurgical systems, frameless stereotactic has been increasingly used for tumor resection or biopsy without the use of stereotactic frame. Frameless stereotactic for functional surgery has been recently developed with the accuracy comparable to frame-based stereotactic surgery. The authors report the surgical technique of frameless functional stereotactic for the treatment of movement disorders.

Complicaciones quirúrgicas y mecánicas de la estimulación cerebral profunda en el tratamiento de la enfermedad de Parkinson / Surgical and mechanical complications of deep cerebral stimulation in Parkinson's diseases treatment

Introducción: La estimulación cerebral del núcleo subtalámico es un método eficaz y en expansión para el tratamiento de la enfermedad de Parkinson. Aunque se trata de un procedimiento poco invasivo puede presentar complicaciones quirúrgicas y efectos secundarios indeseables. Método: entre marzo de 2001 y diciembre de 2006, hemos implantado 208 electródos subtalámicos en 100 pacientes afectados de enfermedad de Parkinson, en el Hospital Clínico de Santiago de Compostela. Se revisan las complicaciones quirúrgicas y mecánicas o de hardware presentadas tanto durante la cirugía como en el seguimiento que osciló entre 6 y 63 meses (media 27 meses). No hubo fallecimientos ni se perdió el control de ningún paciente. Resultados: se presentaron 20 complicaciones quirúrgicas en los 100 pacientes (20 por ciento) y 9 complicaciones mecánicas (9 por ciento). Las complicaciones quirúrgicas más habituales fueron 8 casos de malposición o migración de los electródos, 5 casos de infección, 3 hemorragias subcorticales y 3 episodios convulsivos. Entre las complicaciones mecánicas se presentaron 7 episodios de disfunción de la batería y 2 casos de ruptura del electródo. Conclusiones: la estimulación cerebral profunda es un tratamiento a largo plazo que requiere de controles continuados. Las complicaciones quirúrgicas y de hardware no suponen un riesgo vital importante sin embargo tienen un coste económico importante.

Introducction: Subthalamic nucleus stimulation for patients with medically refractory Parkinson disease is expanding. Although nonablative and minimally invasive, this procedure may give rise to many surgical complications and side effects. Methods: from March 2001 to December 2006, 208 subthalamic stimulator devices were implanted in 100 patients with Parkinson disease at Clinic Hospital of Santiago de Compostela (Spain). The author prospectively documented surgical and hardware complications occurring at the time of surgery and at subsequent neurologic and surgical evaluations for an average of 27 months, ranging from 6 to 63 months. No patients were lost to follow-up or died. Results: There were 20 adverse events related to surgery in 100 patients (20 percent)and 9 hardware-related complications (9 percent). The most important surgical complications were 8 electrodes migration or malposition, 5 infections, 3 subcortical haemorrhages and 3 seizures whereas the hardware complications were 7 stimulator malfunction and 2 electrode breakages. Conclusions: Deep brain stimulation is a life-long therapy that requires a life-long follow-up. Complications due to surgery or hardware are not life-threatening but are expensive in economic terms and in terms of patients suffering.

Acoustic voice assessment in Parkinson's disease patients submitted to posteroventral pallidotomy

O uso prolongado da levodopa na doença de Parkinson (DP) pode ocasionar alterações em seu rendimento e possibilitou o interesse no ressurgimento da palidotomia. Contudo, complicações pós-operatórias podem ocorrer. OBJETIVO: O presente estudo tem por objetivo avaliar alguns parâmetros acústicos da voz de pacientes com DP pré e pós a realização da palidotomia posteroventral METODO: foram avaliados 12 pacientes com PD submetidos a avaliação neurológica e da voz durante as fases off e on do uso da levodopa, nos momentos pré-operatório, no primeiro e no terceiro mês pós-operatório. Os pacientes foram avaliados com base na escala UPDRS - item motor - e por meio dos parâmetros acústicos da voz - f0, NHR, jitter, PPQ, Shimmer, APQ (usando o software MDVP - Kay Elemetrics - 3700). RESULTADOS: Na fase off o escore UPDRS revelou tendência de melhora no 1º pós-operatório e na fase on piora. Os parâmetros acústicos shimmer e APQ apresentaram melhora. CONCLUSÃO: Este estudo mostrou que a palidotomia resulta em discreta melhora no uso funcional da comunicação dos pacientes com DP.

Efficient Induction of Dopaminergic Neurons from Embryonic Stem Cells for Application to Parkinson's Disease

For cell replacement therapy of neurodegenerative diseases such as Parkinson's disease (PD), methods for efficiently generating midbrain dopaminergic (DA) neurons from embryonic stem (ES) cells have been investigated. Two aspects of DA neuron generation are considered: genetic modification and manipulation of culture conditions. A transcription factor known as critical for development of DA neurons, Nurr1, was introduced into ES cells to see how they facilitate the generation of DA neurons from ES cells. Also, two culture procedures, the 5-stage method and stromal cell-derived inducing activity (SDIA) method, were used for ES cell differentiation. Using the 5-stage method, we and others previously demonstrated that Nurr1-overexpressing ES cells, under treatment of signaling molecules such as SHH and FGF8 followed by treatment of ascorbic acid, can differentiate into DA neurons with a high efficiency (> 60% of TH+/Tuj1+ neurons). Furthermore, using the SDIA method with treatment of signaling molecules, we found that Nurr1-overexpressing ES cells can differentiate to DA neurons with the highest efficiency ever reported (~90% of TH+/Tuj1+ neurons). Importantly, our semi-quantitative and real-time PCR analyses demonstrate that all known DA marker genes (e.g., TH, AADC and DAT) were up-regulated in Nurr1- overexpressing ES cells when compared to the na ve ES cells. These cells produced increased dopamine compared to na ve D3 cells after differentiation. In the in vivo context after transplantation, the genetically modified ES cells also showed the highly increased dopaminergic neuronal phenotypes. Thus, the combination of genetic engineering and appropriate culture conditions provides a useful tool to generate a good cell source from ES cells for cell replacement therapy of degenerative diseases such as PD.

Tratamento cirúrgico da doença de Parkinson / Neurosurgical treatment of movement disorders

Neste capítulo são abordados o histórico do tratamento cirúrgico da doença de Parkinson, as principais indicações e contra-indicações dos diversos tipos de procedimentos...

Considerações acerca do tratamento cirúrgico da doença de Parkinson / Reflections on surgical treatment of Parkinson's disease

A doença de Parkinson é responsável por cerca de 80 por cento dos casos de parkinsonismo. Uma grande variedade de procedimentos neurocirúrgicos tem sido proposta através dos anos, e os recentes avanços permitiram a simplificação dos procedimentos ablativos e por neuroestimulação dos alvos anatômicos, agora melhor definidos neurofisiologicamente. Os autores fazem revisão do tratamento neurocirúrgico da doença de Parkinson, descrevem a anatomia dos gânglios da base e sua fisiopatologia, fazendo correlação com possíveis alvos cirúrgicos. As técnicas cirúrgicas são descritas, suas indicações e principais complicações. O tratamento neurocirúrgico constitui técnica adicional, capaz de melhorar significativamente a qualidade de vida dos pacientes

Experimental study on heterograft of glomus cells of carotid body for hemiparkinsonian rats / 华中科技大学学报（医学）（英德文版）

To observe the effects of heterograft of glomus cells of carotid body on hemiparkinsonian rat models, rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the right dopaminergic neurons of substantia nigra received intrastriatal glomus cells heterograft. Apomorphine-induced rotation was monitored for 30 min at various time points after grafting. The striata were cut and examined for dopamine content by HPLC and for immunohistochemical staining of tyrosine hydroxylase positive neurons (TH+) at the end of the experiments. The results showed that apomorphine-induced rotational behavior was significantly reduced for 12 weeks and the dopamine contents were significantly elevated after grafting (P < 0.01), and TH+ cells survived better. The present study demonstrates that intrastriatal heterograft of glomus cells within carotid body in rats with 6-OHDA-elicited lesions could reduce apomorphine-induced rotational behavior and elevate the dopamine contents and numbers of TH+ cell surviving within striatum, and can serve as a new and effective alternative for Parkinson disease.