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.

Jules Bernard Luys: from a description of the subthalamic nucleus to hypnotism / Jules Bernard Luys: da descrição do núcleo subtalâmico ao hipnotismo

ABSTRACT The authors review the role of Jules Bernard Luys in the discovery of the subthalamic nucleus (STN) over 150 years ago. The relationships between the STN and movement disorders, particularly hemiballismus and Parkinson's disease, are well known. The academic life of Jules Bernard Luys can be divided into two periods: a brilliant start as a neuroanatomist, culminating in the discovery of the STN, followed by a second period marked by a shift in his academic activity and an increased interest in topics such as hysteria, hypnotism and, eventually, esotericism.

RESUMO Os autores revisam o papel de Jules Bernard Luys na descoberta do núcleo subtalâmico (NST) há mais de 150 anos. As relações da NST com distúrbios do movimento, em particular o hemibalismo e a doença de Parkinson, são bem conhecidas. A vida acadêmica de Jules Bernard Luys pode ser dividida em duas fases: a primeira, um brilhante começo de sua carreira como neuroanatomista, culminando na descoberta do NST, seguido por um segundo período marcado por uma mudança em sua atividade acadêmica, e maior interesse em tópicos como histeria, hipnotismo e finalmente esoterismo.

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).

Medical management after subthalamic stimulation in Parkinson's disease: a phenotype perspective / Manejo medicamentoso após estimulação subtalâmica na doença de Parkinson: uma perspectiva fenotípica

Abstract Subthalamic nucleus deep brain stimulation (STN DBS) is an established treatment that improves motor fluctuations, dyskinesia, and tremor in Parkinson's disease (PD). After the surgery, a careful electrode programming strategy and medical management are crucial, because an imbalance between them can compromise the quality of life over time. Clinical management is not straightforward and depends on several perioperative motor and non-motor symptoms. In this study, we review the literature data on acute medical management after STN DBS in PD and propose a clinical algorithm on medical management focused on the patient's phenotypic profile at the perioperative period. Overall, across the trials, the levodopa equivalent daily dose is reduced by 30 to 50% one year after surgery. In patients taking high doses of dopaminergic drugs or with high risk of impulse control disorders, an initial reduction in dopamine agonists after STN DBS is recommended to avoid the hyperdopaminergic syndrome, particularly hypomania. On the other hand, a rapid reduction of dopaminergic agonists of more than 70% during the first months can lead to dopaminergic agonist withdrawal syndrome, characterized by apathy, pain, and autonomic features. In a subset of patients with severe dyskinesia before surgery, an initial reduction in levodopa seems to be a more reasonable approach. Finally, when the patient's phenotype before the surgery is the severe parkinsonism (wearing-off) with or without tremor, reduction of the medication after surgery can be more conservative. Individualized medical management following DBS contributes to the ultimate therapy success.

Resumo A estimulação cerebral profunda do núcleo subtalâmico (ECP NST) é um tratamento estabelecido para doença de Parkinson (DP), que leva à melhora das flutuações motoras, da discinesia e do tremor. Após a cirurgia, deve haver uma estratégia cuidadosa de programação da estimulação e do manejo medicamentoso, pois um desequilíbrio entre eles pode comprometer a qualidade de vida. O gerenciamento clínico não é simples e depende de vários sintomas motores e não motores perioperatórios. Nesta revisão, discutimos os dados da literatura sobre o tratamento clínico agudo após a ECP NST na DP e propomos um algoritmo clínico baseado no perfil fenotípico do paciente no período perioperatório. Em geral, nos estudos clínicos, a dose diária equivalente de levodopa é reduzida em 30 a 50% um ano após a cirurgia. Em pacientes que recebem altas doses de medicações dopaminérgicas ou com alto risco de impulsividade, recomenda-se redução inicial do agonista dopaminérgico após a ECP NST, para evitar síndrome hiperdopaminérgica, particularmente a hipomania. Por outro lado, uma rápida redução de agonistas dopaminérgicos em mais de 70% durante os primeiros meses pode levar à síndrome de abstinência do agonista dopaminérgico, com apatia, dor e disautonomia. Em pacientes com discinesia grave antes da cirurgia, é recomendada redução inicial na dose de levodopa. Finalmente, quando o fenótipo do paciente antes da cirurgia é o parkinsonismo grave (flutuação motora) com ou sem tremor, a redução da medicação após a cirurgia deve ser mais conservadora. O tratamento médico individualizado após a ECP contribui para o sucesso final da terapia.

How is cognition in subthalamic nucleus deep brain stimulation Parkinson's disease patients? / Como é a Cognição em Pacientes com Doença de Parkinson com Estimulação Cerebral Profunda no Núcleo Subtalâmico? Uma Revisão Sistemática

Abstract The impairments in cognitive functions such as memory, executive function, visuospatial skills and language in Parkinson's disease (PD) are drawing increasing attention in the current literature. Studies dedicated to investigating the relationship between subthalamic nucleus deep brain stimulation (STN-DBS) and cognitive functioning are contradictory. This systematic review aims to analyze the impact on the cognitive functioning of patients with PD and STN-DBS. Articles published in the 2007-2017 period were retrieved from the Medline/Pubmed databases using PRISMA criteria. The analysis of 27 articles revealed many conflicting results, precluding a consensus on a cognitive functioning standard and hampering the establishment of a neuropsychological profile for PD patients who underwent STN-DBS surgery. Further studies investigating this relationship are needed.

Resumo As deficiências nas funções cognitivas, como memória, função executiva, habilidades visuoespaciais e linguagem na doença de Parkinson (DP), estão cada vez mais chamando a atenção na literatura atual. Estudos dedicados a investigar a relação entre a estimulação cerebral profunda do núcleo subtalâmico (ECP-NST) e o funcionamento cognitivo são contraditórios. Esta revisão sistemática tem como objetivo analisar o impacto no funcionamento cognitivo de pacientes com DP e ECP-NST. Os artigos foram coletados nas bases de dados Medline / Pubmed publicadas no período de 2007-2017, utilizando os critérios do PRISMA. Após a análise de 27 artigos observou-se muitos resultados opostos, não sendo possível convencionar um padrão de funcionamento cognitivo o que dificulta o estabelecimento de um perfil neuropsicológico para pacientes com essa doença que foram submetidos à cirurgia de ECP-NST, sendo necessários mais estudos.

Deep Brain Stimulation for the Treatment of Juvenile Parkinsonism: Case Report

Juvenile parkinsonism (JP) is characterized by the clinical manifestation of Parkinson syndrome before the age of 21 years old. This entity is often associated with genetic mutations. After all the possibilities of clinical treatment have been exhausted, surgical treatment is recommended, performed via deep brain stimulation (DBS) in the subthalamic nucleus (STN) or in the internal segment of the globus pallidus (GPi). The present study aimed to report the case of a patient with JP who underwent DBS in the STN with good clinical response. Neuromodulation via DBS is an option for the treatment of JP. However, since this entity is very rare, and even more peculiar when treated surgically, more studies are necessary to evaluate DBS used to control refractory manifestations and levodopa-induced dyskinesia, as well as surgical complications that may occur, aiming to gather more knowledge of the surgical management of JP. Despite the dysarthria after the DBS, the patient presented a satisfactory response regarding the symptoms, corroborated by the Parkinson's Disease Questionnaire (PDQ-39) score, which was 61.19% before the procedure, and decreased to 21.05% 14 months after the DBS.

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.

Pilot Study for Considering Subthalamic Nucleus Anatomy during Stimulation Using Directional Leads

OBJECTIVE: Directional leads are used for deep brain stimulation (DBS). Two of the four contacts of the leads are divided into three parts, enabling controlled stimulation in a circumferential direction. The direction of adverse effects evoked by DBS in the subthalamic nucleus (STN) and stimulation strategies using directional leads were evaluated. METHODS: Directional leads were implanted into the bilateral STN of six parkinsonian patients (1 man, 5 women; mean age 66.2 years). The contact centers were located within the upper border of the STN, and the locations were identified electrically using microrecordings. Adverse effects were evaluated with electrical stimulation (30 μs, 130 Hz, limit 11 mA) using the directional part of each lead after surgery, and the final stimulation direction was investigated. Unified Parkinson's disease rating scale (UPDRS) scores were evaluated before and after DBS. RESULTS: Fifty-six motor and four sensory symptoms were evoked by stimulation; no adverse effect was evoked in 14 contacts. Motor and sensory symptoms were evoked by stimulation in the anterolateral direction and medial to posterolateral direction, respectively. Stimulation in the posteromedial direction produced adverse effects less frequently. The most frequently used contacts were located above the STN (63%), followed by the upper part of the STN (32%). The mean UPDRS part III and dyskinesia scores decreased after DBS from 30.2 ± 11.7 to 7.2 ± 2.9 and 3.3 ± 2.4 to 0.5 ± 0.8, respectively. CONCLUSION: The incidence of adverse effects was low for the posteromedial stimulation of the STN. Placing the directional part of the lead above the STN may facilitate the control of dyskinesia.

Design and implementation of postoperative evaluation pipeline of deep brain stimulation by multimodality imaging / 生物医学工程学杂志

Deep brain stimulation (DBS) surgery is an important treatment for patients with Parkinson's disease in the middle and late stages. The accuracy of the implantation of electrode at the location of the nuclei directly determines the therapeutic effect of the operation. At present, there is no single imaging method that can obtain images with electrodes, nuclei and their positional relationship. In addition, the subthalamic nucleus is small in size and the boundary is not obvious, so it cannot be directly segmented. In this paper, a complete end-to-end DBS effect evaluation pipeline was constructed using magnetic resonance (MR) data of T1, T2 and SWI weighted by DBS surgery. Firstly, the images of preoperative and postoperative patients are registered and normalized to the same coordinate space. Secondly, the patient map is obtained by non-rigid registration of brain map and preoperative data, as well as the preoperative nuclear cluster prediction position. Then, a three-dimensional (3D) image of the positional relationship between the electrode and the nucleus is obtained by using the electrode path in the postoperative image and the result of the nuclear segmentation. The 3D image is helpful for the evaluation of the postoperative effect of DBS and provides effective information for postoperative program control. After analysis, the algorithm can achieve a good registration between the patient's DBS surgical image and the brain map. The error between the algorithm and the expert evaluation of the physical coordinates of the center of the thalamus is (1.590 ± 1.063) mm. The problem of postoperative evaluation of the placement of DBS surgical electrodes is solved.

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.

Turning on the Left Side Electrode Changed Depressive State to Manic State in a Parkinson's Disease Patient Who Received Bilateral Subthalamic Nucleus Deep Brain Stimulation: A Case Report

No previous reports have described a case in which deep brain stimulation elicited an acute mood swing from a depressive to manic state simply by switching one side of the bilateral deep brain stimulation electrode on and off. The patient was a 68-year-old woman with a 10-year history of Parkinson's disease. She underwent bilateral subthalamic deep brain stimulation surgery. After undergoing surgery, the patient exhibited hyperthymia. She was scheduled for admission. On the first day of admission, it was clear that resting tremors in the right limbs had relapsed and her hyperthymia had reverted to depression. It was discovered that the left-side electrode of the deep brain stimulation device was found to be accidentally turned off. As soon as the electrode was turned on, motor impairment improved and her mood switched from depression to mania. The authors speculate that the lateral balance of stimulation plays an important role in mood regulation. The current report provides an intriguing insight into possible mechanisms of mood swing in mood disorders.

Deep brain stimulation in Parkinson's disease: analysis of the variation in final stimulating lead placement based on multi-tract electrode recordings

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (SNT) is a treatment modality for Parkinson's Disease (PD). Either single central trajectory tract or multiple selected trajectory tracts based on microelectrode recordings (MER) are used for the placement of the final stimulating electrodes. This study aims to explore how many times trajectory tracts, other than the central tract are used for final lead placement.Methods: Retrospective analysis of a randomly selected convenience sample of 24 subjects from patients who had DBS by a single neurosurgeon. After MRI and CT assessment, planning using a stereotactic frame for variable trajectory placement of temporary electrodes and MER that was the basis for site and tract selection for the final electrode placements used for DBS. Results: Twenty four patients had 47 DBS electrodes placed: 1 unilateral and 23 bilateral. The central tract was used in 45 (95.75%) of these cases. The central trajectory tract accounted for 30 (63.83%), the anterior trajectory tract for 7 (14.89%), the medial tract for 5 (10.64%), the posterior for 4 (8.51%) and the lateral for 1 (2.13%) of final lead placements. Conclusion: The results of this study based on the predicted best stimulating sites following MER show that alternates to the central trajectory tract are required in 37% of site placements. A comparative study exploring clinical benefit is required to assess if variable electrode trajectory placement based on accurate physiological measurements is superior to single central trajectory placement

Electroacupuncture Alleviates Motor Symptoms and Up-Regulates Vesicular Glutamatergic Transporter 1 Expression in the Subthalamic Nucleus in a Unilateral 6-Hydroxydopamine-Lesioned Hemi-Parkinsonian Rat Model / 神经科学通报·英文版

Previous studies have shown that electroacupuncture (EA) promotes recovery of motor function in Parkinson's disease (PD). However the mechanisms are not completely understood. Clinically, the subthalamic nucleus (STN) is a critical target for deep brain stimulation treatment of PD, and vesicular glutamate transporter 1 (VGluT1) plays an important role in the modulation of glutamate in the STN derived from the cortex. In this study, a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD was treated with 100 Hz EA for 4 weeks. Immunohistochemical analysis of tyrosine hydroxylase (TH) showed that EA treatment had no effect on TH expression in the ipsilateral striatum or substantia nigra pars compacta, though it alleviated several of the parkinsonian motor symptoms. Compared with the hemi-parkinsonian rats without EA treatment, the 100 Hz EA treatment significantly decreased apomorphine-induced rotation and increased the latency in the Rotarod test. Notably, the EA treatment reversed the 6-OHDA-induced down-regulation of VGluT1 in the STN. The results demonstrated that EA alleviated motor symptoms and up-regulated VGluT1 in the ipsilateral STN of hemi-parkinsonian rats, suggesting that up-regulation of VGluT1 in the STN may be related to the effects of EA on parkinsonian motor symptoms via restoration of function in the cortico-STN pathway.

Different outcomes of phonemic verbal fluency in Parkinson's disease patients with subthalamic nucleus deep brain stimulation / Diferentes desfechos na tarefa de fluência verbal fonêmica em pacientes com doença de Parkinson submetidos à estimulação cerebral profunda

ABSTRACT Subthalamic nucleus deep brain stimulation (STN-DBS) is a surgical technique to treat motor symptoms in patients with Parkinson’s disease (PD). Studies have shown that STN-DBS may cause a decline in verbal fluency performance. We aimed to verify the effects of STN-DBS on the performance of phonemic verbal fluency in Brazilian PD patients. Sixteen participants were evaluated on the Unified Parkinson’s Disease Rating Scale - Part III and for phonemic fluency (“FAS” version) in the conditions of on- and off-stimulation. We identified two different patterns of phonemic verbal fluency outcomes. The results indicate that there may be no expected pattern of effect of bilateral STN-DBS in the phonemic fluency, and patients may present with different outcomes for some reason not well understood.

RESUMO A estimulação cerebral profunda do núcleo subtalâmico (ECP-NST) é uma técnica cirúrgica para tratar sintomas motores na doença de Parkinson (DP). Estudos têm mostrado que ECP-NST pode causar um declínio no desempenho de fluência verbal. O objetivo do estudo foi verificar os efeitos da ECP-NST sobre o desempenho da fluência verbal fonêmica em indivíduos brasileiros com DP. Dezesseis participantes foram avaliados quanto ao desempenho motor (UPDRS-III) e à fluência verbal fonêmica (versão “FAS”) nas condições de estimulação ligada e desligada. Identificamos dois padrões diferentes de resultados de fluência verbal fonêmica. Os resultados indicam que pode não haver um padrão esperado de efeito de ECP-NST bilateral na fluência fonêmica, e os pacientes podem apresentar desfechos diferentes de acordo com alguma razão não bem compreendida.

Comparison of Pallidal and Subthalamic Deep Brain Stimulation in Parkinson's Disease: Therapeutic and Adverse Effects

OBJECTIVE: To compare the therapeutic and adverse effects of globus pallidus interna (GPi) and subthalamic nucleus (STN) deep brain stimulation (DBS) for the treatment of advanced Parkinson's disease (PD). METHODS: We retrospectively analyzed the clinical data of patients with PD who underwent GPi (n = 14) or STN (n = 28) DBS surgery between April 2002 and May 2014. The subjects were matched for age at surgery and disease duration. The Unified Parkinson's Disease Rating Scale (UPDRS) scores and levodopa equivalent dose (LED) at baseline and 12 months after surgery were used to assess the therapeutic effects of DBS. Adverse effects were also compared between the two groups. RESULTS: At 12 months, the mean changes in the UPDRS total and part I–IV scores did not differ significantly between the two groups. However, the subscores for gait disturbance/postural instability and dyskinesia were significantly more improved after GPi DBS than those after STN DBS (p = 0.024 and 0.016, respectively). The LED was significantly more reduced in patients after STN DBS than that after GPi DBS (p = 0.004). Serious adverse effects did not differ between the two groups (p = 0.697). CONCLUSION: The patients with PD showed greater improvement in gait disturbance/postural instability and dyskinesia after GPi DBS compared with those after STN DBS, although the patients had a greater reduction in LED after STN DBS. These results may provide useful information for optimal target selection for DBS in PD.

Striatal Glutamate and GABA after High Frequency Subthalamic Stimulation in Parkinsonian Rat

OBJECTIVE: High frequency stimulation (HFS) of the subthalamic nucleus (STN) is recognized as an effective treatment of advanced Parkinson’s disease. However, the neurochemical basis of its effects remains unknown. The aim of this study is to investigate the effects of STN HFS in intact and 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rat model on changes of principal neurotransmitters, glutamate, and gamma-aminobutyric acid (GABA) in the striatum. METHODS: The authors examined extracellular glutamate and GABA change in the striatum on sham group, 6-OHDA group, and 6-OHDA plus deep brain stimulation (DBS) group using microdialysis methods. RESULTS: High-pressure liquid chromatography was used to quantify glutamate and GABA. The results show that HFS-STN induces a significant increase of extracellular glutamate and GABA in the striatum of 6-OHDA plus DBS group compared with sham and 6-OHDA group. CONCLUSION: Therefore, the clinical results of STN-HFS are not restricted to the direct STN targets but involve widespread adaptive changes within the basal ganglia.

Influence of Medication on the Oscillatory and Dynamic Characteristics of Subthalamic Local Field Potentials in Patients with Parkinson's Disease / 生物医学工程学杂志

The dysfunction of subthalamic nucleus is the main cause of Parkinson's disease. Local field potentials in human subthalamic nucleus contain rich physiological information. The present study aimed to quantify the oscillatory and dynamic characteristics of local field potentials of subthalamic nucleus, and their modulation by the medication therapy for Parkinson's disease. The subthalamic nucleus local field potentials were recorded from patients with Parkinson's disease at the states of on and off medication. The oscillatory features were characterised with the power spectral analysis. Furthermore, the dynamic features were characterised with time-frequency analysis and the coefficient of variation measure of the time-variant power at each frequency. There was a dominant peak at low beta-band with medication off. The medication significantly suppressed the low beta component and increased the theta component. The amplitude fluctuation of neural oscillations was measured by the coefficient of variation. The coefficient of variation in 4-7 Hz and 60-66 Hz was increased by medication. These effects proved that medication had significant modulation to subthalamic nucleus neural oscillatory synchronization and dynamic features. The subthalamic nucleus neural activities tend towards stable state under medication. The findings would provide quantitative biomarkers for studying the mechanisms of Parkinson's disease and clinical treatments of medication or deep brain stimulation.

Effects of aging on nitrergic neurons in human striatum and subthalamic nucleus / Efeitos do envelhecimento sobre os neurônios nitrérgicos no estriado e núcleo subtalâmico humano

Nitric oxide (NO) is a major neurotransmitter associated with motor control in basal ganglia. Movement disorders, as essential tremor and Parkinson’s disease, are more prevalent on aged individuals. We investigated the effects of aging on neuronal density and diameter/area of nitrergic neurons in samples of striatum (caudate and putamen) and subthalamic nucleus of 20 human brains from normal subjects, stained by histochemistry for NADPH-diaphorase and immunohistochemistry for neuronal NO synthase. Our data showed aging does not modify the neuronal density and size of nitrergic neurons in striatum and subthalamic nucleus. These findings suggest a lack of association between aging and morphologic changes on nitrergic neurons.

O óxido nítrico (NO) é um importante neurotransmissor associado ao controle motor nos núcleos da base. Os distúrbios de movimento, como tremor essencial e a doença de Parkinson, são mais prevalentes em indivíduos idosos. Nós investigamos os efeitos do envelhecimento sobre a densidade neuronal e diâmetro/área dos neurônios nitrérgicos em amostras de estriado (caudado e putâmen) e núcleo subtalâmico de 20 encéfalos humanos de indivíduos normais, corados pela técnica histoquímica da NADPH-diaforase e imunohistoquímica para a sintase do NO neuronal. Nossos resultados mostraram que o envelhecimento não modifica a densidade neuronal e as dimensões dos neurônios nitrérgicos no estriado e núcleo subtalâmico. Estes achados sugerem uma falta de associação entre envelhecimento e mudanças morfológicas nos neurônios nitrérgicos.