Safety and effectiveness of electromyography-induced rehabilitation treatment after epidural electrical stimulation for spinal cord injury: study protocol for a prospective, randomized, controlled trial.

Epidural electrical stimulation is a new treatment method for spinal cord injury (SCI). Its efficacy and safety have previously been reported. Rehabilitation treatment after epidural electrical stimulation is important to ensure and improve the postoperative efficacy of epidural electrical stimulation in patients with SCI. Considering that electromyography (EMG)-induced rehabilitation treatment can accurately match the muscle contraction of patients with SCI, we designed a study protocol for a prospective, randomized controlled trial. In this trial, on the premise of adjusting the spinal cord electrical stimulator to obtain the maximum EMG signal of the target muscle, patients with SCI receiving epidural electrical stimulation will undergo EMG-induced rehabilitation treatment. Recovery of muscle strength of key muscles, quality of life, safety and therapeutic effects will be monitored. Twenty patients with SCI who are scheduled to undergo epidural electrical stimulation in Shanghai Ruijin Rehabilitation Hospital will be randomly divided into two groups with 10 patients per group. The control group will receive conventional rehabilitation treatment. The EMG-induced rehabilitation group will receive EMG-induced rehabilitation treatment of the target muscles of the upper and lower limbs based on conventional rehabilitation treatment. After rehabilitation treatment, follow up for all patients will occur at 2 weeks and 1, 3 and 6 months. The primary outcome measure of this trial will be evaluation of target muscle recovery using the Manual Muscle Testing grading scale. Secondary outcome measures will include modified Barthel Index scores, integrated EMG values, the visual analogue scale, Spinal Cord Independence Measure scores, and modified Ashworth scale scores. The safety indicator will be the incidence of adverse events. This trial will collect data regarding the therapeutic effects of EMG-induced rehabilitation in patients with SCI receiving epidural electrical stimulation for 6 months after rehabilitation treatment. Findings from this trial will help develop rehabilitation methods in patients with SCI after epidural electrical stimulation. This study protocol was approved by Ethics Committee of Shanghai Ruijin Rehabilitation Hospital (Approval No. RKIRB2022-12) on February 15, 2022 and was registered with Chinese Clinical Trial Registry (registration number: ChiCTR2200061674; date: June 30, 2022). Study protocol version: 1.0.

Deep brain stimulation in post-traumatic dystonia: A case series study.

AIMS: Deep brain stimulation (DBS) has been proposed as an effective treatment for drug-intolerant isolated dystonia, but whether it is also efficacious for posttraumatic dystonia (PTD) is unknown. Reports are few in number and have reached controversial conclusions regarding the efficacy of DBS for PTD treatment. Here, we report a case series of five PTD patients with improved clinical benefit following DBS treatment. METHODS: Five patients with disabling PTD underwent DBS therapy. The clinical outcomes were assessed with the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) at baseline and the last follow-up visit (at more than 12 months). RESULTS: Patients 1 and 3 received unilateral globus pallidus internus (GPi) DBS for contralateral dystonia. The subthalamic nucleus (STN) was chosen as target for patients 2 and 4, due to a lesion located in the globus pallidus. Patient 5 had an electrode in the ventral intermediate nucleus (VIM) for treating predominant tremor of left upper extremity, with unexpected improvement of focal hand dystonia. The scores of BFMDRS movement exhibited favorable improvement in all five patients at the last follow-up, ranging from 52.4% to 78.6%. CONCLUSIONS: Deep brain stimulation may be an effective and safe treatment for medically refractory PTD, but this needs to be confirmed by further studies.

The safety issues and hardware-related complications of deep brain stimulation therapy: a single-center retrospective analysis of 478 patients with Parkinson's disease.

INTRODUCTION: Deep brain stimulation (DBS) is a well-established therapy for the treatment of advanced Parkinson's disease (PD) in patients experiencing motor fluctuations and medication-refractory tremor. Despite the relative tolerability and safety of this procedure, associated complications and unnatural deaths are still unavoidable. METHODS: In this study, hardware-related complications and the causes of unnatural death were retrospectively analyzed in 478 patients with PD who were treated with DBS. RESULTS: The results showed a 3-year survival rate of 98.6% and a 5-year survival rate of 96.4% for patients with PD who underwent DBS treatment at the study center. Pneumonia was the cause of death with the highest frequency. Prophylactic antibiotics and steroids or antihistamine drugs were adopted to reduce the risk of infection. Twenty-two patients (4.6%) experienced hardware-related complications. CONCLUSION: Deaths of PD patients who receive DBS are typically unrelated to the disease itself or complications associated with the surgery. Pneumonia, malignant tumors, asphyxia, and multiple-organ failure are the common causes of death. Swallowing-related problems may be the most important clinical symptom in late-stage PD, as they cannot be stabilized or improved by DBS alone, and are potentially lethal. Although prophylactic antibiotics and steroids or antihistamine drugs may reduce the risk of infection, it is imperative to identify high-risk patients for whom a therapeutic approach not requiring an implantable device is more suitable, for example, pallidotomy and potentially transcranial ultrasound.

Modulations on cortical oscillations by subthalamic deep brain stimulation in patients with Parkinson disease: A MEG study.

OBJECTIVE: The study aimed to explore the modification to cortical oscillations of Parkinson disease (PD) patients by subthalamic nucleus deep brain stimulation (STN DBS). METHODS: With Magnetoencephalogram (MEG) detection, we examined the changes in absolute power spectrum of cortical oscillations in the PD patients with the treatment of STN DBS. RESULTS: The power analysis of PD patients showed a dominant over-synchronization of alpha and beta bands in temporal and occipital areas relative to the healthy control subjects. STN DBS on-state showed marked power increase in the gamma band of PD patients in the frontal and parietal relative to the DBS off-state. The alleviation of motor symptoms by STN DBS negatively correlated to the increase of high gamma oscillation in the right frontal cortex, and also correlated to the suppression of the alpha and beta oscillations in the right temporal cortex. CONCLUSION: The treatment of STN DBS to PD patients might involve the augmentation of gamma activity and suppression of alpha and beta activities in cortical oscillations.

Long-term follow-up of bilateral subthalamic deep brain stimulation for refractory tardive dystonia.

BACKGROUND: No effective treatment for tardive dystonia (TD) has been well established. Deep brain stimulation (DBS) can ameliorate motor manifestations in primary dystonia, and may also be an effective approach for TD. OBJECTIVES: This study aimed to illuminate the long-term efficacy and safety of subthalamic nucleus (STN)-DBS in treating TD. METHODS: Ten patients with refractory TD underwent STN-DBS therapy and were assessed by the Burke-Fahn-Marsden dystonia rating scale (BFMDRS), Abnormal Involuntary Movement Scale (AIMS), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and the Short Form (36) Health Survey (SF-36) at four time points: pre-operation, 1 week post-operation, 6 months post-operation, and at a final long-term postsurgical follow-up time point. RESULTS: The mean follow-up time was 65.6 ± 30.4 months (range, 12-105 months). At the first follow-up, BFMDRS motor and disability scores had improved by 55.9± 28.3% and 62.6± 32.0%, respectively, while AIMS scores improved by 53.3± 26.7%. At the second follow-up, BFMDRS motor and disability scores improved further, by 87.3± 17.0% and 84.3% ± 22.9%, respectively, while AIMS scores improved by 88.4 ± 16.1%. At the last follow-up, this benefit was sustained and had plateaued. Quality of life was improved significantly at the long-term follow-up, and the HAMA and HAMD scores displayed a significant reduction that persisted after the first follow-up. CONCLUSION: STN-DBS may be an effective and acceptable procedure for TD, leading to persistent and significant improvement in both movement and psychiatric symptoms.

Ubiquitin-protein ligase E3C promotes glioma progression by mediating the ubiquitination and degrading of Annexin A7.

The ubiquitin-protein ligase E3C (UBE3C) belongs to the E3 ligase enzyme family and implicates in the ubiquitin-proteasome pathway, thus regulates physiological and cancer-related processes. Here, we investigated the expression and roles of UBE3C in glioma. We demonstrated that UBE3C was overexpressed in glioma tissues and cell lines. Inhibition of UBE3C expression in glioma cells significantly decreased cell migration and invasion in vitro. Mechanistically, we disclosed that UBE3C physically interacted with and ubiquitinated tumor suppressor gene annexin A7 (ANXA7), resulting in ubiquitination and degradation of ANXA7. Our results also revealed that increased UBE3C expression was accompanied by a reduction in ANXA7 protein expression in glioma tissues, but not ANXA7 mRNA. Importantly, the inhibition of ANXA7 expression in gliomas cells with UBE3C interference could rescue the cell invasion. Clinically, UBE3C overexpression significantly correlated with high-grade tumors (p < 0.05), poor overall survival, and early tumor recurrence. Thus, our data reveal that high UBE3C expression contributes to glioma progression by ubiquitination and degradation of ANXA7, and thus presents a novel and promising target for glioma therapy.

Effects of bilateral subthalamic nucleus stimulation on resting-state cerebral glucose metabolism in advanced Parkinson's disease.

BACKGROUND: The major neuropathological symptoms of Parkinson's disease (PD) consist of a loss of pigmented dopaminergic neurons in the substantia nigra and the presence of Lewy bodies. This study was to investigate the effects of bilateral subthalamic nucleus (STN) stimulation on resting-state cerebral glucose metabolism in advanced PD, and investigate the mechanism of deep brain stimulation (DBS). METHODS: Seven consecutive advanced PD patients (4 men and 3 women, mean age 64 +/- 4 years, mean H-Y disability rating 4.4 +/- 0.65) receiving bilateral STN DBS underwent 18F-fluorodeoxyglucose (18F-FDG)/positron-emission tomography (PET) examinations at rest both preoperatively and one month postoperatively, with STN stimulation still on. The unified PD rating scale was used to evaluate the clinical state under each condition. Statistical parametric mapping (SPM) was used to investigate the regional cerebral metabolic rates of glucose (rCMRGlu) during STN stimulation, and to compare these values to rCMRGlu preoperation. RESULTS: STN stimulation clearly improved clinical symptoms in all patients. A significant increase in rCMRGlu was found in the bilateral lentiform nucleus, brainstem (midbrain and pons), bilateral premotor area (BA6), parietal-occipital cortex, and anterior cingulated cortex, and a marked decrease in rCMRGlu was noted in the left limbic lobe and bilateral inferior frontal cortex (P < 0.05). CONCLUSION: Bilateral STN stimulation may activate the projection axon from the STN, improving clinical symptoms in advanced PD patients by improving both ascending and descending pathways from the basal ganglia and increasing the metabolism of higher-order motor control in the frontal cortex.

Association between vitamin D receptor gene polymorphisms and susceptibility to Parkinson's disease: a meta-analysis.

Previous studies have reported an association between vitamin D receptor (VDR) gene polymorphisms and Parkinson's disease (PD), but the results were controversial. To explore whether VDR gene polymorphisms have an effect on PD risk, we performed this meta-analysis to evaluate the association between three VDR gene polymorphisms (Bsml, Apal, Taql) and PD susceptibility. We performed a systematic literature search for articles published up to February 2014 in multiple databases and selected seven eligible studies. Four studies were included for each polymorphism. Odds ratios (ORs) as well as their corresponding 95% confidence intervals (CIs) were used to estimate the association between VDR gene polymorphisms and PD risk in four phenotype models. Subgroup analysis and publication bias were also performed. Heterogeneity analysis and sensitivity analysis were performed if necessary. We failed to detect any association between Apal, Bsml, Taql polymorphisms and PD susceptibility in all four genetic models. In subgroup analysis grouped by ethnicity, no significant association was detected. The present meta-analysis indicates that the VDR genetic polymorphisms Bsml, Apal and Taql are not associated with susceptibility to PD. Because of the limited number of included studies, the results should be cautiously interpreted. More carefully designed studies are needed to verify our results.

Metabolic imaging of deep brain stimulation in anorexia nervosa: a 18F-FDG PET/CT study.

OBJECTIVES: Anorexia nervosa (AN), a disorder of unknown etiology, has the highest mortality rate of any psychiatric disorder. Drawing the brain metabolic pattern of AN may help to target the core biological and psychological features of the disorder and to perfect the diagnosis and recovery criteria. In this study, we used 18F-FDG PET to show brain metabolic network for AN. METHODS: Glucose metabolism in 6 AN patients and 12 age-matched healthy controls was studied using 18F-FDG PET. SPM2 was used to compare brain metabolism in AN patients with that in healthy controls. Four of 6 AN patients took deep brain stimulation (DBS) targeted in nucleus accumbens (NAcc). About 3 to 6 months after the surgery, the 4 AN patients took another 18F-FDG PET scan to assess the change in brain glucose metabolism. RESULTS: The SPM (statistical parametric mapping ) analysis showed hypermetabolism in the frontal lobe (bilateral, BA10, BA11, BA47), the limbic lobe (bilateral, hippocampus, and amygdala), lentiform nucleus (bilateral), left insula (BA13), and left subcallosal gyrus (BA25). It also showed hypometabolism in the parietal lobe (bilateral, BA7, BA40). The hypermetabolism in frontal lobe, hippocampus, and lentiform nucleus decreased after NAcc-DBS. CONCLUSIONS: The changes in brain glucose metabolism illustrated the brain metabolic pattern in AN patients. Furthermore, the pattern can be modulated by NAcc-DBS, which confirmed specificity of the pattern. The regions with altered metabolism could interconnect to form a network and integrate information related to appetite. Our study may provide information for targeting the potential candidate brain regions for understanding the pathophysiology of AN and assessing the effects of existing and future treatment approaches.