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).

Landmarks for the Location of the Subthalamic Nucleus Using Magnetic Resonance Imaging

Deep brain stimulation has become an option for advanced Parkinson's disease treatment since the 1990s, but the first reports are from Benabid's team, a French neurosurgeon, in the 1980s. The subthalamic nucleus (STN), more specifically its dorsolateral portion, is the most commonly stimulated brain area. One of the major aspects for a good surgical result is the accurate location of this target. Therefore, the present article aimed to identify landmarks that facilitate and refine the location of the STN using nuclear magnetic resonance imaging (NMRI) of the skull. In order to achieve this goal, a search for articles was performed using the PubMed and Science Direct online databases, and articles regarding the use of NMRI to target STN were included. The precise location of the dorsolateral portion of the STN is fundamental to achieve the best possible effect on motor symptoms and to minimize side effects. One of the most used location methods is the NMRI, associated or not with tomography or ventriculography. The location strategies can be classified as direct and indirect. Landmarks are among the indirect strategies, and the most important ones (red nucleus, Sukeroku sign, dent internal capsule sign, supramammillary commissure, mammillothalamic tract, and interpeduncular cistern) are described in the present article. The various landmarks can be combined to locate with more accuracy the dorsolateral portion of the STN and the ideal position of the electrodes to achieve the best possible clinical result.

Subthalamic Nucleus: Neuroanatomical Review

Discovered in 1865 by Jules Bernard Luys, the subthalamic nucleus is a set of small nuclei located in the diencephalon, inferior to the thalamus and superior to the substantia nigra, that can be visualized in a posterior coronal section. Histologically, it consists of neurons compactly distributed and filled with a large number of blood vessels and sparse myelinated fibers. This review presents an analysis of this anatomical region, considering what is most recent in the literature. Subthalamic neurons are excitatory and use glutamate as the neurotransmitter. In healthy individuals, these neurons are inhibited by nerve cells located in the side globus pallidus. However, if the fibers that make up the afferent circuit are damaged, the neurons become highly excitable, thus causing motor disturbances that can be classified as hyperkinetic, for example ballism and chorea, or hypokinetic, for example Parkinson disease (PD). The advent of deep brain stimulation has given the subthalamic nucleus great visibility. Studies reveal that the stimulation of this nucleus improves themotor symptoms of PD.

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.

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.

Lesion of the subthalamic nucleus reverses motor deficits but not death of nigrostriatal dopaminergic neurons in a rat 6-hydroxydopamine-lesion model of Parkinson's disease

The objective of the present study was to determine whether lesion of the subthalamic nucleus (STN) promoted by N-methyl-D-aspartate (NMDA) would rescue nigrostriatal dopaminergic neurons after unilateral 6-hydroxydopamine (6-OHDA) injection into the medial forebrain bundle (MFB). Initially, 16 mg 6-OHDA (6-OHDA group) or vehicle (artificial cerebrospinal fluid - aCSF; Sham group) was infused into the right MFB of adult male Wistar rats. Fifteen days after surgery, the 6-OHDA and SHAM groups were randomly subdivided and received ipsilateral injection of either 60 mM NMDA or aCSF in the right STN. Additionally, a control group was not submitted to stereotaxic surgery. Five groups of rats were studied: 6-OHDA/NMDA, 6-OHDA/Sham, Sham/NMDA, Sham/Sham, and Control. Fourteen days after injection of 6-OHDA, rats were submitted to the rotational test induced by apomorphine (0.1 mg/kg, ip) and to the open-field test. The same tests were performed again 14 days after NMDA-induced lesion of the STN. The STN lesion reduced the contralateral turns induced by apomorphine and blocked the progression of motor impairment in the open-field test in 6-OHDA-treated rats. However, lesion of the STN did not prevent the reduction of striatal concentrations of dopamine and metabolites or the number of nigrostriatal dopaminergic neurons after 6-OHDA lesion. Therefore, STN lesion is able to reverse motor deficits after severe 6-OHDA-induced lesion of the nigrostriatal pathway, but does not protect or rescue dopaminergic neurons in the substantia nigra pars compacta.

Current surgical treatment of Parkinson's disease

There has been a renaissance in the surgical management of Parkinson's disease. This has been due to long-term effects of levodopa and a better understanding of the basal ganglia and its circuitry. Ablative surgery and neurostimulation are the only realistic surgical options at present. Although surgical treatments, such as ablation and stimulation are effective, they are not useful for stopping the progression or restoring the system. Neural transplantation helps restore the system by using a number of techniques. Targets mostly used are in the thalamus, globus pallidus and subthalamic nucleus. A number of factors must be considered including patient's age, disability and his wishes. Globus pallidus stimulation might be preferable for patients who suffer from dyskinesia as a major source of disability. Pallidotomy might be appropriate in cases where frequent stimulator adjustments are impractical. Subthalamic nucleus stimulation is more suitable for patients with significant off periods and in younger patients in whom it may be desirable to maintain intact circuitry. Fetal neural transplantation, stem cell transplantation, xenotransplantation, adrenal medullary transplantation and transplantation of genetically engineered cells are at various stages of development and research. Ethical issues surrounding these process are likely to arouse strong emotions and have to be carefully considered

Current surgical treatment of Parkinson's disease

There has been a renaissance in the surgical management of Parkinson's disease. This has been due to long-term effects of levodopa and a better understanding of the basal ganglia and its circuitry. Ablative surgery and neurostimulation are the only realistic surgical options at present. Although surgical treatments, such as ablation and stimulation are effective, they are not useful for stopping the progression or restoring the system. Neural transplantation helps restore the system by using a number of techniques. Targets mostly used are in the thalamus, globus pallidus and subthalamic nucleus. A number of factors must be considered including patient's age, disability and his wishes. Globus pallidus stimulation might be preferable for patients who suffer from dyskinesia as a major source of disability. Pallidotomy might be appropriate in cases where frequent stimulator adjustments are impractical. Subthalamic nucleus stimulation is more suitable for patients with significant off periods and in younger patients in whom it may be desirable to maintain intact circuitry. Fetal neural transplantation, stem cell transplantation, xenotransplantation, adrenal medullary transplantation and transplantation of genetically engineered cells are at various stages of development and research. Ethical issues surrounding these process are likely to arouse strong emotions and have to be carefully considered