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BACKGROUND: Postural abnormalities (PA) are common in the advanced stages of Parkinson's disease (PD), but effective therapies are lacking. A few studies suggested that spinal cord stimulation (SCS) could be a potential therapy whereas its effect is still uncertain. We aimed to investigate whether SCS had potential for benefiting PD patients with PA. METHODS: T8-12 SCS was operated on six PD patients with PA and all patients were followed for one year. Evaluations were made before and after SCS. Moreover, three patients were tested separately with SCS on-state and off-state to confirm the efficacy of SCS. RESULTS: Improvements in lateral trunk flexion degree, anterior thoracolumbar flexion degree and motor function were found after SCS. The improvements diminished while SCS was turned off. CONCLUSIONS: Lower thoracic SCS may be effective for improving PA in PD patients, but further studies are needed to confirm this conclusion. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900024326, Registered on 6th July 2019; https://www.chictr.org.cn/showproj.aspx?proj=40835 .
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Doença de Parkinson , Equilíbrio Postural , Estimulação da Medula Espinal , Humanos , Estimulação da Medula Espinal/métodos , Doença de Parkinson/terapia , Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologia , Projetos Piloto , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Equilíbrio Postural/fisiologia , Resultado do TratamentoRESUMO
Postsynaptic proteins play critical roles in synaptic development, function, and plasticity. Dysfunction of postsynaptic proteins is strongly linked to neurodevelopmental and psychiatric disorders. SAP90/PSD95-associated protein 4 (SAPAP4; also known as DLGAP4) is a key component of the PSD95-SAPAP-SHANK excitatory postsynaptic scaffolding complex, which plays important roles at synapses. However, the exact function of the SAPAP4 protein in the brain is poorly understood. Here, we report that Sapap4 knockout (KO) mice have reduced spine density in the prefrontal cortex and abnormal compositions of key postsynaptic proteins in the postsynaptic density (PSD) including reduced PSD95, GluR1, and GluR2 as well as increased SHANK3. These synaptic defects are accompanied by a cluster of abnormal behaviors including hyperactivity, impulsivity, reduced despair/depression-like behavior, hypersensitivity to low dose of amphetamine, memory deficits, and decreased prepulse inhibition, which are reminiscent of mania. Furthermore, the hyperactivity of Sapap4 KO mice could be partially rescued by valproate, a mood stabilizer used for mania treatment in humans. Together, our findings provide evidence that SAPAP4 plays an important role at synapses and reinforce the view that dysfunction of the postsynaptic scaffolding protein SAPAP4 may contribute to the pathogenesis of hyperkinetic neuropsychiatric disorder.
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Mania , Proteínas do Tecido Nervoso , Humanos , Camundongos , Animais , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Mania/metabolismo , Mania/patologia , Sinapses/fisiologia , Proteína 4 Homóloga a Disks-Large/metabolismo , Camundongos Knockout , Proteínas dos Microfilamentos/metabolismoRESUMO
BACKGROUND: The subthalamic nucleus (STN) is an effective deep brain stimulation target for Parkinson disease (PD) and obsessive-compulsive disorder and has been implicated in reward and motivational processing. In this study, we assessed the STN and prefrontal oscillatory dynamics in the anticipation and receipt of reward and loss using a task commonly used in imaging. MATERIALS AND METHODS: We recorded intracranial left subthalamic local field potentials from deep brain stimulation electrodes and prefrontal scalp electroencephalography in 17 patients with PD while they performed a monetary incentive delay task. RESULTS: During the expectation phase, enhanced left STN delta-theta activity was observed in both reward and loss vs neutral anticipation, with greater STN delta-theta activity associated with greater motivation specifically to reward. In the consummatory outcome phase, greater left STN delta activity was associated with a rewarding vs neutral outcome, particularly with more ventral contacts along with greater delta-theta coherence with the prefrontal cortex. We highlight a differential activity in the left STN to loss vs reward anticipation, demonstrating a distinct STN high gamma activity. Patients with addiction-like behaviors show lower left STN delta-theta activity to loss vs neutral outcomes, emphasizing impaired sensitivity to negative outcomes. CONCLUSIONS: Together, our findings highlight a role for the left STN in reward and loss processing and a potential role in addictive behaviors. These findings emphasize the cognitive-limbic function of the STN and its role as a physiologic target for neuropsychiatric disorders.
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Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Motivação , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiologia , Recompensa , Eletroencefalografia , Estimulação Encefálica Profunda/métodosRESUMO
Spinal cord stimulation (SCS) is receiving increasing interests for treating pain and gait disorders in patients with Parkinson's disease (PD). In an SCS study, it is hard to apply a double-blind approach, especially at low frequencies, as the stimulation normally induces paresthesia which can be perceived by the patient. We herein demonstrate a case treated with SCS in which a blinding design was accomplished by an accidental dislocation of a stimulation lead. A 73-year-old man with PD was admitted to our hospital because of relapsed low back pain. This was due to the dislocation of a previously implanted SCS lead, which caused a decrease in its effectiveness in alleviating pain (from 81 to 43% measured by King's Parkinson's Disease Pain Scale) and improving gait (from 35 to 28% measured by the timed up and go test). A second SCS surgery using a paddle lead solved this problem, with improvements in pain and gait rebounded to 81 and 45%. In this case, the paresthesia induced by SCS (using either a paddle lead or percutaneous leads) was below the threshold of perception when the patient was sitting and standing, and a dislocation of one previously implanted percutaneous lead did not cause evident changes in his sensation of paresthesia. At last follow-up, the patient's quality of life had improved by 40% as measured by the 8-item Parkinson's Disease questionnaire (PDQ-8). This study could serve partly as a proof that low-frequency SCS is effective in improving pain as well as gait problems in PD patients, which was unlikely a result of a placebo effect.
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Migração de Corpo Estranho/terapia , Transtornos Neurológicos da Marcha/terapia , Dor Lombar/terapia , Medição da Dor/métodos , Doença de Parkinson/terapia , Estimulação da Medula Espinal/métodos , Idoso , Método Duplo-Cego , Migração de Corpo Estranho/complicações , Transtornos Neurológicos da Marcha/etiologia , Humanos , Dor Lombar/etiologia , Masculino , Manejo da Dor/métodos , Doença de Parkinson/complicações , Equilíbrio Postural/fisiologia , Qualidade de Vida , Estimulação da Medula Espinal/instrumentaçãoRESUMO
Silica aerogels, which are constructed with silica nanoparticles and numerous nanoscale pores, have many outstanding attributes, but they are usually brittle and hydrophilic. For the construction of a robust aerogel, the novel polyhedral oligomeric silsesquioxane (POSS) was introduced to prepare a series of aerogels possessing particles covered with elastic cushion to improve the mechanical property. The multialkoxy POSS, which possessed stiff Si-O-Si nanocages and flexible alkyl chains, was synthesized via thiol-ene click chemistry. After a facile and efficient approach, a partially ordered structure of SiO2 nanoparticles and organic elastic cushion would form spontaneously within the aerogels. With the POSS as the only precursor, several outstanding attributes were achieved in a single aerogel such as high specific surface area (SSA), high compression strength, high compression modulus, and noticeable compression flexibility. Meanwhile, the aerogel was superhydrophobic of which the contact angle (CA) was higher than 153°. Moreover, the potential application of oil-water separation is also presented.
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Under the new coronavirus epidemic, the implementation of public health measures has generated some resistance in countries around the world. The essence of examining the human rights claims of those who oppose the epidemic is that they have a too narrow understanding of individual human rights and ignore the obligation implications of human rights itself. From the historical point of view, health and epidemic prevention is the objective necessity of the survival and development of human society; From the ethical point of view, the joint fight against the epidemic is the moral obligation of the coordinated development of individuals and society. From the normative point of view, the management of infectious diseases is the basic consensus established by many international conventions. To correct the narrow understanding of individual human rights concept, the global human rights concept should be established in pandemic governance, and the concept of human health community should be shaped in the pandemic convention to build governance consensus, implement the same health concept to clarify the scope of governance, implement the principle of common but differentiated responsibilities, and strengthen the participation of individuals and communities in public health governance to improve governance paths. To shape a more reasonable and effective pandemic governance order.
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Objectives: The aim of this study was to investigate the impact of nonmotor symptoms (NMS) on the quality of life (QoL) outcome after subthalamic nucleus deep brain stimulation (STN-DBS) at the 1-year follow-up. Methods: Ninety-three patients diagnosed with Parkinson's disease (PD), who underwent subthalamic nucleus deep brain stimulation (STN-DBS) between April 2020 and August 2021, were included in this study. Demographic information was gathered through a self-designed questionnaire. The severity of both motor and non-motor symptoms, along with the quality of life (QoL), was assessed using the Unified Parkinson's Disease Rating Scale-III (UPDRS-III), Nonmotor Symptoms Scale (NMSS), and 8-item Parkinson's Disease Questionnaire (PDQ-8), respectively. Results: Significant differences were observed in the UPDRS-III score, NMSS summary index (SI), and subscores of six domains (sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, urinary, and sexual function) between the baseline and the 6- and 12-month follow-ups. The correlation analysis revealed positive correlations between the preoperative NMSS SI and subscores of seven domains (cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastrointestinal, and urinary) and ΔPDQ-8. Moreover, the preoperative PDQ-8 SI (ß = 0.869, P < 0.001) and the preoperative attention/memory subscore (ß = -0.154, P = 0.026) were predictive of the postsurgery improvement in quality of life (QoL). Conclusion: Deep brain stimulation (DBS) led to an improvement in the patients' nonmotor symptoms (NMS) at the 1-year follow-up, along with a correlation observed between NMS and the patients' quality of life (QoL). Notably, the severity of preoperative attention/memory problems emerged as the most significant predictor of NMS influencing the QoL outcome after STN-DBS at the 1-year follow-up.
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BACKGROUND: Psychiatric comorbidities are common in Parkinson's disease (PD) and may change with high-frequency stimulation targeting the subthalamic nucleus. Numerous accounts indicate subthalamic alpha-frequency oscillation is implicated in emotional processing. While intermittent alpha-frequency (10Hz) stimulation induces positive emotional effects, with more ventromedial contacts inducing larger effects, little is known about the subacute effect of ventral 10Hz subthalamic stimulation on emotional processing. OBJECTIVE/HYPOTHESIS: To evaluate the subacute effect of 10Hz stimulation at bilateral ventral subthalamic nucleus on emotional processing in PD patients using an affective task, compared to that of clinical-frequency stimulation and off-stimulation. METHODS: Twenty PD patients with bilateral subthalamic deep brain stimulation for more than six months were tested with the affective task under three stimulation conditions (10Hz, 130Hz, and off-stimulation) in a double-blinded randomized design. RESULTS: While 130Hz stimulation reduced arousal ratings in all patients, 10Hz stimulation increased arousal selectively in patients with higher depression scores. Furthermore, 10Hz stimulation induced a positive shift in valence rating to negative emotional stimuli in patients with lower apathy scores, and 130Hz stimulation led to more positive valence to emotional stimuli in the patients with higher apathy scores. Notably, we found correlational relationships between stimulation site and affective rating: arousal ratings increase with stimulation from anterior to posterior site, and positive valence ratings increase with stimulation from dorsal to ventral site of the ventral subthalamic nucleus. CONCLUSIONS: Our findings highlight the distinctive role of 10Hz stimulation on subjective emotional experience and unveil the spatial organization of the stimulation effect.
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Apatia , Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Nível de Alerta , Emoções/fisiologia , Doença de Parkinson/terapia , Doença de Parkinson/psicologia , Núcleo Subtalâmico/fisiologiaRESUMO
Introduction: Deep brain stimulation (DBS) studies in Parkinson's Disease (PD) targeting the subthalamic nucleus (STN) have characterized its spectral properties across cognitive processes. In emotional evaluation tasks, specific alpha frequency (8-12 Hz) event-related de-synchronization (ERD) (reduced power) has been demonstrated. The time-locked stimulation of STN relative to stimuli onset has shown subjective positive valence shifts with 10 Hz but not with 130 Hz. However, neurophysiological effects of stimulation on power modulation have not been investigated. We aim to investigate effects of acute stimulation of the right STN on concurrent power modulation in the contralateral STN and frontal scalp EEG. From our previous study, we had a strong a priori hypothesis that negative imagery without stimulation would be associated with alpha ERD; negative imagery with 130 Hz stimulation would be also associated with alpha ERD given the lack of its effect on subjective valence ratings; negative imagery with 10 Hz stimulation was to be associated with enhanced alpha power given the shift in behavioral valence ratings. Methods: Twenty-four subjects with STN DBS underwent emotional picture-viewing tasks comprising neutral and negative pictures. In a subset of these subjects, the negative images were associated with time-locked acute stimulation at either 10 or 130 Hz. Power of signals was estimated relative to the baseline and subjected to non-parametric statistical testing. Results: As hypothesized, in 130 Hz stimulation condition, we show a decrease in alpha power to negative vs. neutral images irrespective of stimulation. In contrast, this alpha power decrease was no longer evident in the negative 10 Hz stimulation condition consistent with a predicted increase in alpha power. Greater beta power in the 10 Hz stimulation condition along with correlations between beta power across the 10 Hz stimulation and unstimulated conditions suggest physiological and cognitive generalization effects. Conclusion: Acute alpha-specific frequency stimulation presumably was associated with a loss of this expected decrease or desynchronization in alpha power to negative images suggesting the capacity to facilitate the synchronization of alpha and enhance power. Acute time-locked stimulation has the potential to provide causal insights into the spectral frequencies and temporal dynamics of emotional processing.
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[This corrects the article DOI: 10.3389/fnhum.2021.604433.].
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High cervical spinal cord stimulation (HCSCS) was found to have therapeutic effects on Parkinsonian gait disturbance. However, the results were inconsistent and confounded with symptoms of pain. This study aimed to reveal the gait and dysarthric effects of HCSCS in PD (Parkinson's disease) and MSA-P (Parkinson variant of multiple system atrophy) patients without pain. Three PD and five MSA-P patients without painful comorbidities were assessed for gait performance and speech before SCS surgery and at 3- and 6-month follow-up. Stride length and the time spent in the Timed Up-and-Go task showed little change after HCSCS surgery. Overall voice quality (measured by dysphonia severity index) and perceptual speech intelligence improved significantly at 3 months, but improvements slightly diminished at 6 months postoperatively. Change in quality of life (measured by 8-item Parkinson's disease questionnaire) was also notable at 3 months but narrowed over time following HCSCS. In conclusion, HCSCS showed therapeutic effects in improving the dysarthria but not gait disturbance in pain-free PD and MSA-P patients.
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The habenula is an epithalamic structure implicated in negative reward mechanisms and plays a downstream modulatory role in regulation of dopaminergic and serotonergic functions. Human and animal studies show its hyperactivity in depression which is curtailed by the antidepressant response of ketamine. Deep brain stimulation of habenula (DBS) for major depression have also shown promising results. However, direct neuronal activity of habenula in human studies have rarely been reported. Here, in a cross-sectional design, we acquired both spontaneous resting state and emotional task-induced neuronal recordings from habenula from treatment resistant depressed patients undergoing DBS surgery. We first characterise the aperiodic component (1/f slope) of the power spectrum, interpreted to signify excitation-inhibition balance, in resting and task state. This aperiodicity for left habenula correlated between rest and task and which was significantly positively correlated with depression severity. Time-frequency responses to the emotional picture viewing task show condition differences in beta and gamma frequencies for left habenula and alpha for right habenula. Notably, alpha activity for right habenula was negatively correlated with depression severity. Overall, from direct habenular recordings, we thus show findings convergent with depression models of aberrant excitatory glutamatergic output of the habenula driving inhibition of monoaminergic systems.
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Transtorno Bipolar , Transtorno Depressivo Maior , Habenula , Animais , Estudos Transversais , Transtorno Depressivo Maior/terapia , Habenula/fisiologia , Humanos , Índice de Gravidade de DoençaRESUMO
Camptocormia is a common and often debilitating postural deformity in Parkinson's disease (PD). Few treatments are currently effective. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) shows potential in treating camptocormia, but evidence remains limited to case reports. We herein investigate the effect of GPi-DBS for treating camptocormia in a retrospective PD cohort. Thirty-six consecutive PD patients who underwent GPi-DBS were reviewed. The total and upper camptocormia angles (TCC and UCC angles) derived from video recordings of patients who received GPi-DBS were used to compare camptocormia alterations. Correlation analysis was performed to identify factors associated with the postoperative improvements. DBS lead placement and the impact of stimulation were analyzed using Lead-DBS software. Eleven patients manifested pre-surgical camptocormia: seven had lower camptocormia (TCC angles ≥ 30°; TCC-camptocormia), three had upper camptocormia (UCC angles ≥ 45°; UCC-camptocormia), and one had both. Mean follow-up time was 7.3 ± 3.3 months. GPi-DBS improved TCC-camptocormia by 40.4% (angles from 39.1° ± 10.1° to 23.3° ± 8.1°, p = 0.017) and UCC-camptocormia by 22.8% (angles from 50.5° ± 2.6° to 39.0° ± 6.7°, p = 0.012). Improvement in TCC angle was positively associated with pre-surgical TCC angles, levodopa responsiveness of the TCC angle, and structural connectivity from volume of tissue activated to somatosensory cortex. Greater improvement in UCC angles was seen in patients with larger pre-surgical UCC angles. Our study demonstrates potential effectiveness of GPi-DBS for treating camptocormia in PD patients. Future controlled studies with larger numbers of patients with PD-related camptocormia should extend our findings.
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BACKGROUND: Emotional processing is a core cognitive process cutting across neuropsychiatric disorders. Understanding the neurophysiological features underlying depressive symptoms and their sensitivity to modulation is critical to modifying emotional bias. The subthalamic nucleus (STN), targeted in Parkinson's disease, shows a late alpha desynchronization to affective stimuli. We targeted this alpha desynchronization using a novel stimulation protocol asking if brief alpha (10 Hz) frequency stimulation time-locked to unpleasant imagery might influence subjective emotion. METHODS: A total of 27 patients with Parkinson's disease were recruited. The first study tested patients (n = 16) on affective stimuli with STN local field potential recordings assessed bilaterally without stimulation. In the second study, patients (n = 24) were tested on two affective tasks comparing negative and neutral stimuli paired with acute right-STN stimulation, with one of the negative conditions stimulated briefly for 1 second at either 130 Hz or 10 Hz. The subjects rated valence and arousal of negative and neutral stimuli. RESULTS: We confirmed greater alpha desynchronization in both negative and positive affect relative to neutral in the right STN. Using acute stimulation of the right STN, we show a critical interaction effect between ratings, stimulation, and frequency; alpha frequency stimulation increased the subjective pleasantness of negative imagery, particularly with ventromedial contacts. Higher depression scores were associated with a positive bias to 10-Hz but not 130-Hz stimulation. CONCLUSIONS: We highlight the potential of brief alpha frequency subthalamic stimulation to reduce negative emotional bias. This finding provides mechanistic insights underlying subjective emotional valence and has implications for the management of depression using neuromodulation.
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Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Nível de Alerta , Emoções , Humanos , Doença de Parkinson/terapiaRESUMO
Objective: To investigate the correlation between preoperative response to the L-dopa challenge test and efficacy of deep brain stimulation (DBS) on motor function in Parkinson's disease (PD). Methods: We retrospectively reviewed the data of 38 patients with idiopathic PD who underwent DBS surgery with a median follow-up duration of 7 months. Twenty underwent bilateral globus pallidus interna (GPi) DBS, and 18 underwent bilateral subthalamic nucleus (STN) DBS. The Movement Disorder Society Unified Parkinson Disease Rating Scale-Motor Part (MDS UPDRS-III) was assessed before surgery and at the last follow-up in different medication and stimulation conditions, respectively. Results: Pearson's correlation analysis revealed a positive correlation between preoperative L-dopa challenge responsiveness and GPi-DBS responsiveness on the total score (R 2 = 0.283, p = 0.016) but not on the non-tremor total score (R 2 = 0.158, p = 0.083) of MDS UPDRS-III. Such correlation remained significant (R 2' = 0.332, p = 0.010) after controlling for age at the time of surgery as confounding factor by partial correlation analysis. The preoperative L-dopa challenge responsiveness was significantly correlated with the tremor-controlling outcome of GPi-DBS (R 2 = 0.390, p = 0.003). In contrast, we found a positive correlation between preoperative L-dopa challenge responsiveness and STN-DBS responsiveness on the non-tremor total score (R 2 = 0.290, p = 0.021), but not on the total score (R 2 = 0.130, p = 0.141) of MDS UPDRS-III. The partial correlation analysis further demonstrated that the predictive value of preoperative L-dopa challenge responsiveness on the non-tremor motor outcome of STN-DBS was eliminated (R 2' = 0.120, p = 0.174) after controlling for age at the time of surgery as confounding factor. Interpretation: The short-term predictive value of preoperative response to the L-dopa challenge test for the motor outcome of GPi-DBS in PD was systematically described. Our findings suggest: (1) a solid therapeutic effect of GPi-DBS in treating L-dopa-responsive tremors; (2) a negative effect of age at the time of surgery on motor outcomes of STN-DBS, (3) a possible preference of STN- to GPi-DBS in L-dopa-resistant tremor control, and (4) a possible preference of GPi- to STN-DBS in elderly PD patients who have a satisfactory dopamine response.
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BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) has been reported to be effective for camptocormia in Parkinson's disease (PD). However, the association between clinical effectiveness and the stimulated volumes or structural connectivity remains unexplored. OBJECTIVE: To investigate the effectiveness of STN-DBS for treating camptocormia in PD and its association with volumes of tissue activated (VTA) and structural connectivity. METHODS: We reviewed video recordings of patients who had undergone STN-DBS. The total and upper camptocormia (TCC and UCC) angles were measured to quantify changes in camptocormia. The Movement Disorders Society Unified Parkinson's Disease Rating Scale III (MDS-UPDRS III) was used to assess motor symptoms. Pre- and postoperative brain images were collected for modeling volume of VTA and structural connectivity using Lead-DBS software. RESULTS: Participants included 36 patients with PD (8 with TCC-camptocormia and 2 with UCC-camptocormia) treated with bilateral STN-DBS. After surgery, patients showed a significant improvement in postural alignment at follow-up (mean follow-up duration: 6.0±2.2 months). In the entire sample, higher structural connectivity to the right supplementary motor area (SMA) and right lateral premotor cortex along the dorsal plane (PMd) was associated with larger postsurgical improvements in axial signs and TCC angles after stimulation was turned on. In patients diagnosed with camptocormia, larger improvement in camptocormia angles after STN-DBS was associated with a larger VTA overlap with STN (Râ=â0.75, pâ=â0.032). CONCLUSION: This study suggests that both VTA overlap with STN and structural connectivity to cortical motor regions are associated with the effectiveness of STN-DBS for managing camptocormia in PD.
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Estimulação Encefálica Profunda , Córtex Motor/patologia , Atrofia Muscular Espinal/terapia , Rede Nervosa/patologia , Avaliação de Resultados em Cuidados de Saúde , Doença de Parkinson/terapia , Curvaturas da Coluna Vertebral/terapia , Núcleo Subtalâmico , Adulto , Idoso , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Atrofia Muscular Espinal/etiologia , Atrofia Muscular Espinal/patologia , Atrofia Muscular Espinal/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Doença de Parkinson/complicações , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Índice de Gravidade de Doença , Curvaturas da Coluna Vertebral/etiologia , Curvaturas da Coluna Vertebral/patologia , Curvaturas da Coluna Vertebral/fisiopatologiaRESUMO
INTRODUCTION: Previous studies have shown that subthalamic nucleus (STN) and unilateral globus pallidus interna (GPi) are similarly effective in the deep brain stimulation (DBS) treatment of motor symptoms. However, the counterintuitively more common clinical application of STN DBS makes us hypothesize that STN is superior to GPi in the treatment of motor symptoms. METHODS: In this prospective, double-blind, randomized crossover study, idiopathic PD patients treated with combined unilateral STN and contralateral GPi DBS (STN in one brain hemisphere and GPi in the other) for 2 to 3 years were enrolled. The MDS UPDRS-III total score and subscale scores for axial and bilateral limb symptoms were assessed preoperatively and at 2- to 3-year follow-up in four randomized, double-blinded conditions: (1) Med-STN+GPi-, (2) Med-STN-GPi+, (3) Med+STN+GPi-, and (4) Med+STN-GPi+. RESULTS: Eight patients had completed 30 trials of assessment. Compared with the preoperative Med- state, in the Med-STN+GPi- condition, the cardinal symptoms in both sides of the body were all improved. In the Med-STN-GPi+ condition, symptoms of the GPi-stim limb were improved, while only tremor was improved on the ipsilateral side, although all axial symptoms showed aggravation. Compared with the preoperative Med+ state, in the Med+STN+GPi- state, cardinal symptoms were improved on both sides, except that tremor was worsened on the STN-stim side. In the Med+STN-GPi+ state, the overall motor symptoms were aggravated compared with the preoperative Med+ state. Most axial symptoms worsened at acute unilateral STN or GPi DBS onset, compared to both preoperative Med- and Med+ states. No side effects associated with this study were seen. CONCLUSIONS: Improvement in motor symptoms was greater in all sub-scores favoring STN. The effects of STN+ were seen on both sides of the body, while GPi+ mainly acted on the contralateral side.
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BACKGROUND: Emerging evidence indicates that iron distribution is heterogeneous within the substantia nigra (SN) and it may reflect patient-specific trait of Parkinson's Disease (PD). We assume it could account for variability in motor outcome of subthalamic nucleus deep brain stimulation (STN-DBS) in PD. OBJECTIVE: To investigate whether SN susceptibility features derived from radiomics with machine learning (RA-ML) can predict motor outcome of STN-DBS in PD. METHODS: Thirty-three PD patients underwent bilateral STN-DBS were recruited. The bilateral SN were segmented based on preoperative quantitative susceptibility mapping to extract susceptibility features using RA-ML. MDS-UPDRS III scores were recorded 1-3 days before and 6 months after STN-DBS surgery. Finally, we constructed three predictive models using logistic regression analyses: (1) the RA-ML model based on radiomics features, (2) the RA-ML+LCT (levodopa challenge test) response model which combined radiomics features with preoperative LCT response, (3) the LCT response model alone. RESULTS: For the predictive performances of global motor outcome, the RA-ML model had 82% accuracy (AUC = 0.85), while the RA-ML+LCT response model had 74% accuracy (AUC = 0.83), and the LCT response model alone had 58% accuracy (AUC = 0.55). For the predictive performance of rigidity outcome, the accuracy of the RA-ML model was 80% (AUC = 0.85), superior to those of the RA-ML+LCT response model (76% accuracy, AUC = 0.82), and the LCT response model alone (58% accuracy, AUC = 0.42). CONCLUSION: Our findings demonstrated that SN susceptibility features from radiomics could predict global motor and rigidity outcomes of STN-DBS in PD. This RA-ML predictive model might provide a novel approach to counsel candidates for STN-DBS.
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BACKGROUND: Deep brain stimulation (DBS) for Parkinson's disease (PD) has evolved as a well-established treatment in neurosurgery, and identifying appropriate surgical candidates could contribute to better DBS outcomes. The Florida Surgical Questionnaire for Parkinson Disease (FLASQ-PD) is a reasonable screening tool for assessing DBS candidacy in PD patients; however, a Chinese version of FLASQ-PD is needed for functional neurosurgery units in China. In this study, we translated the FLASQ-PD to Chinese and assessed its reliability and validity for Chinese PD patients. METHODS: The FLASQ-PD was translated before the study formally started. A single-center retrospective analysis of FLASQ-PD was performed at the Ruijin Hospital, affiliated with Shanghai Jiaotong University School of Medicine, between July and December 2019. The Unified Parkinson Disease Rating Scale III (UPDRS-III) was also used to assess PD patients on and off medication. All patients were evaluated for surgical candidacy by specialists. RESULTS: Overall, 115 PD patients, 25 with parkinsonism and six with multiple system atrophy were consecutively included. Internal consistency of the Chinese FLASQ-PD was roughly adequate (Cronbach's alpha = 0.664). There were significant differences in mean total scores of the Chinese FLASQ-PD between the diagnostic (Kruskal-Wallis H value = 37.450, p ≤ 0.001) and surgery-candidacy groups (H = 48.352, p ≤ 0.001). Drug improvements in UPDRS-III scores were mildly correlated with the Chinese FLASQ-PD scores in the surgery-ready group (Pearson correlation = 0.399, p=0.001). CONCLUSIONS: The Chinese FLASQ-PD, which is a simple and efficient screening tool for clinicians, was developed and initially validated in this retrospective single-center study.
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BACKGROUND: Subthalamic nucleus (STN) and globus pallidus interna (GPi) are the most effective targets in deep brain stimulation (DBS) treatment for Parkinson disease (PD). However, the individualized selection of targets remains a clinical challenge. OBJECTIVE: To combine unilateral STN and contralateral GPi stimulation (STN DBS in one brain hemisphere and GPi DBS in the other) to maximize the clinical advantages of each target while inducing fewer adverse side effects in selected patients with PD because each target has its own clinical effects and risk profiles. METHODS: We reviewed the clinical outcomes of 8 patients with idiopathic PD treated with combined unilateral STN and contralateral GPi DBS. Clinical outcome assessments, focusing on motor and nonmotor symptoms, were performed at baseline and 6-mo and 12-mo follow-up. We performed the assessments under the following conditions: medication on and off (bilateral stimulation on and off and unilateral STN stimulation on). RESULTS: Patients showed a significant improvement in motor symptoms, as assessed by the Unified Parkinson Disease Rating Scale III (UPDRS-III) and Timed Up-and-Go Test (TUG), in the off-medication/on-stimulation state at 6-mo and 12-mo follow-up. Also, patients reported a better quality of life, and their intake of levodopa was reduced at 12-mo follow-up. In the on-medication condition, bilateral stimulation was associated with an improvement in axial symptoms, with a 64% improvement in measures of gait and falls at 12-mo follow-up. No irreversible adverse side effects were observed. CONCLUSION: Our findings suggest that combined unilateral STN and contralateral GPi DBS could offer an effective and well-tolerated DBS treatment for certain PD patients.