Motor Improvement Research Articles

Evaluating a motor progression connectivity model across Parkinson's disease stages.

Stimulation of a specific site in the dorsolateral subthalamic nucleus (STN) was recently associated with slower motor progression in Parkinson's Disease (PD), based on the deep brain stimulation (DBS) in early-stage PD pilot clinicaltrial. Here, subject-level visualizations are presented of this early-stage PD dataset to further describe the relationship between active contacts and motor progression. This study also evaluates whether stimulation of the sweet spot and connectivity model associated with slower motor progression is alsoassociated with improvements in long-term motor outcomes in patients with advanced-stage PD. Active contacts of the early-stage PD cohort (N = 14) were analyzed alongside the degree of two-year motor progression. Sweet spot and connectivity models derived from the early-stage PD cohort were then used to determine how well they can estimate the variance inlong-term motor outcomes in an independent STN-DBS cohort of advanced-stage PD patients (N = 29). In early-stage PD, proximity of stimulation to the dorsolateral STN wasassociated with slower motor progression. In advanced-stage PD, stimulation proximity to the early PD connectivity model and sweet spot were associated with better long-term motor outcomes (R = 0.60, P < 0.001; R = 0.37, P = 0.046, respectively). Results suggest stimulation of a specific site in the dorsolateral STN isassociated with both slower motor progression and long-term motor improvements in PD.

β-asarone protects against age-related motor decline via activation of SKN-1/Nrf2 and subsequent induction of GST-4

Decelerating motor decline is important for promoting healthy aging in the elderly population. Acorus tatarinowii Schott is a traditional Chinese medicine that contains β-asarone as a pharmacologically active constituent. We found that β-asarone can decelerate motor decline in various age groups of Caenorhabditis elegans, while concurrently prolonging their lifespan and modulating synaptic transmission. To understand the mechanisms of its efficacy in motor improvement, we investigated and discovered that mitochondrial fragmentation, a marker for aging, is delayed after β-asarone treatment. Moreover, their efficacy is blocked by dysfunctional mitochondria. Corresponding to their role in regulating mitochondrial homeostasis, we found that SKN-1/Nrf2 and GST-4 are critical in the β-asarone treatment, and they appear to be activated via the insulin/IGF-1 signaling pathway. Well-developed intestinal microvilli are required for this process. Our study demonstrates the efficacy and mechanism of β-asarone treatment in age-related motor decline, contributing to the discovery of drugs for achieving healthy aging.

Clemastine enhances exercise-induced motor improvement in hypoxic ischemic rats

Neonatal hypoxic ischemia (HI) occurs owing to reduced cerebral oxygen levels and perfusion during the perinatal period. Brain injury after HI triggers neurological manifestations such as motor impairment, and the improvement of impaired brain function remains challenging. Recent studies suggest that cortical myelination plays a role in motor learning, but its involvement in motor improvement after HI injury is not well understood. This study aimed to investigate the impact of myelination on motor improvement following neonatal HI injury. We employed a modified Rice-Vannucci model; the right common carotid artery of postnatal day 7 (P7) Wistar rats was isolated and divided, and the rats were then exposed to hypoxic condition (90 min, 8 % O2). A total of 101 rats (66 males) were divided into four groups: trained-HI (n = 38), trained-Sham (n = 16), untrained-HI (n = 31), and untrained-Sham (n = 16). The trained groups underwent rotarod-based exercise training from P22 to P41 (3 days per week). Structural analysis using magnetic resonance imaging and immunohistochemistry (n = 6 per group) revealed increased fractional anisotropy and myelin density in the primary somatosensory cortex of the trained-HI group. We further evaluated the effect of myelination promotion on rotarod performance by administering clemastine, a myelination-promoting drug, via daily intraperitoneal injections. Clemastine did not enhance motor improvement in untrained-HI rats. However, clemastine-administered trained-HI rats (n = 7) exhibited significantly improved motor performance compared to both saline-administered trained-HI rats (n = 11) and clemastine-administered untrained-HI rats (n = 7). These findings suggest that myelination may be a key mechanism in motor improvement after HI injury and that combining exercise training with clemastine administration could be an effective therapeutic strategy for motor improvement following HI injury.

An Update on Spinal Cord Injury and Current Management

» Spinal cord injury is associated with increased lifelong cost and decreased life expectancy.» Current treatment guidelines have been limited to studies of small effect sizes and limited availability of randomized control trials.» Recovery is best correlated with the initial American Spinal Injury Association impairment scale grade with A and B less likely to recover regarding ambulation as compared with C and D grades.» Surgical intervention within less than 24 hours, especially in the cervical spine, has been associated with some motor improvement.» The use of mean arterial pressure goals and steroids to maintain perfusion and decrease secondary injury requires further study to elucidate clearer evidence-based results.

Safety and efficacy of adipose-derived mesenchymal stem cell therapy in elderly Parkinson's disease patients: an intermediate-size expanded access program

ObjectiveThis intermediate-size expanded access program aimed to evaluate safety and clinical efficacy of multiple intravenous infusions of autologous, Hope Biosciences adipose-derived mesenchymal stem cell (HB-adMSC) therapy in elderly patients with Parkinson's disease (PD). MethodsTen eligible participants (aged 76–95 years) received six intravenous infusions each with 200MM autologous HB-adMSCs over 18 weeks, with the end of study (EOS) at week 26. Safety was assessed through adverse events (AEs) and serious adverse events (SAEs). Efficacy was measured through improvements in both motor and non-motor symptoms, utilizing scales including Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts I-IV, Parkinson's Disease Questionnaire-39 (PDQ-39), Parkinson's disease Fatigue Scale (PFS-16), Patient Health Questionnaire-9 (PHQ-9), and Visual Analog Scale (VAS). Analysis employed paired t-tests and Minimal Clinically Important Difference (MCID) thresholds for the patient-reported outcomes. ResultsMost AEs (37 out of 46) were mild in severity, with 5 SAEs reported, none attributed to the drug. No deaths occurred. Despite lack of statistical significance across the efficacy endpoints, modest yet clinically meaningful improvements with effect size > 0.3 were observed in several secondary efficacy endpoints (MDS-UPDRS part I & III, PDQ-39, and PHQ-9) at the EOS, nearing or surpassing the established MCID values. ConclusionsThe administration of autologous 200MM HB-adMSCs was found to be safe and well-tolerated in the elderly PD population. Although not achieving statistical significance, modest clinical improvements were noted across multiple secondary endpoints. These findings underscore the safety profile of the treatment in elderly patients and highlight the importance of evaluating clinical relevance alongside statistical measures for meaningful patient outcomes. Further investigation with a larger, randomized, placebo-controlled design is warranted to validate these observations.

An acceptability and feasibility investigation of a community-based motor program for autistic children with moderate and high support needs

BackgroundGeneral motor impairments are ubiquitous in Autism and are positively correlated with autism symptom severity. This study assessed the feasibility and acceptability of a 13-week community-based motor program for autistic children with moderate and high support needs (MHS). MethodIn this exploratory single arm within-subject study, 10 autistic children with MHS, ages 4–10 years, completed a community-based motor program delivered in a one-on-one format by therapists. Feasibility was determined through recruitment, retention, attendance, enjoyment, engagement and useability of motor, physical activity (PA), and behavioural assessment tools. Thematic analysis evaluated post-intervention semi-structured parent interviews. ResultsHigh program attendance and retention were demonstrated, and therapists reported child engagement and enjoyment were high. Identified themes revealed parents perceived unexpected substantial positive impacts including improvements in social, motor, and behavioural outcomes. They highly valued both the program and the therapeutic relationships fostered within it. Although parents of the children with the higher support needs reported the most substantial improvements, these children were unable to score on motor assessments due to difficulties following instructions and off-task behaviours. Additionally, only four participants wore an accelerometer-based PA monitor. ConclusionsThis community-based motor program was considered feasible and acceptable by the children’s parents, and qualitative findings provided valuable insights into clinical practice for children with MHS. However, recruitment challenges and assessment tools being unfeasible for children with higher support needs led to low participant numbers. Future evaluations should explore alternative assessment measures and study designs, given the challenges associated with studying such a heterogenous and complex group.

The contribution of physical exercise to leukemia and lymphoma in children: a scoping review.

The overall contribution of physical exercise on the management of disabling consequences of leukemia and lymphoma in children is missing. The aim of this scoping review (ScoR) was to systematically collect, map and present the current research evidence concerning studies reporting data on physical exercise among children with leukemia and lymphoma. This ScoR was performed by adopting recommendations of the 2020 version of the "Joanna Briggs Institute Methodological Guidance", along with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews. PubMed, Scopus, and the Central (Cochrane) were searched up to December 2023. Original studies were included, and results were presented numerically and thematically. One hundred twelve articles were identified through the search; 14 studies met the inclusion criteria. Publications have increased over the years. Most of the studies were conducted in Western countries. 11 articles (79%) owned to primary research (seven RCTs, and four observational studies), and 3 studies (21%) were systematic reviews. The overall sample size was of 293 individuals. 1 study included a mixed population of leukemias and lymphomas, while the others included only children with leukemia. The features of physical exercise were well described, including details on duration of treatment, frequency of exercises sessions, and duration of sittings. The studies indicated physical exercise as a contributor to the improvement of motor abilities and quality of life. More studies including outcome measures that assess disability are recommended. More evidence on the impact of physical exercise in children with lymphoma is needed.

IpsiHand Brain-Computer Interface Therapy Induces Broad Upper Extremity Motor Rehabilitation in Chronic Stroke.

Chronic hemiparetic stroke patients have very limited benefits from current therapies. Brain-computer interface (BCI) engaging the unaffected hemisphere has emerged as a promising novel therapeutic approach for chronic stroke rehabilitation. This study investigated the effectiveness of contralesionally-controlled BCI therapy in chronic stroke patients with impaired upper extremity motor function. We further explored neurophysiological features of motor recovery driven by BCI. We hypothesized that BCI therapy would induce a broad motor recovery in the upper extremity, and there would be corresponding changes in baseline theta and gamma oscillations, which have been shown to be associated with motor recovery. Twenty-six prospectively enrolled chronic hemiparetic stroke patients performed a therapeutic BCI task for 12 weeks. Motor function assessment data and resting state electroencephalogram signals were acquired before initiating BCI therapy and across BCI therapy sessions. The Upper Extremity Fugl-Meyer assessment served as a primary motor outcome assessment tool. Theta-gamma cross-frequency coupling (CFC) was computed and correlated with motor recovery. Chronic stroke patients achieved significant motor improvement in both proximal and distal upper extremity with BCI therapy. Motor function improvement was independent of Botox application. Theta-gamma CFC enhanced bilaterally over the C3/C4 motor electrodes and positively correlated with motor recovery across BCI therapy sessions. BCI therapy resulted in significant motor function improvement across the proximal and distal upper extremities of patients, which significantly correlated with theta-gamma CFC increases in the motor regions. This may represent rhythm-specific cortical oscillatory mechanism for BCI-driven rehabilitation in chronic stroke patients. Advarra Study: https://classic.clinicaltrials.gov/ct2/show/NCT04338971 and Washington University Study: https://classic.clinicaltrials.gov/ct2/show/NCT03611855.

Reduced subthalamic and subthalamic-cortical coherences associated with the therapeutic carryover effect of coordinated reset deep brain stimulation

Coordinated reset deep brain stimulation (CR DBS), a promising treatment for Parkinson’s disease (PD), is hypothesized to desynchronize neuronal populations. However, little in vivo data probes this hypothesis. In a parkinsonian nonhuman primate, we found that subthalamic CR DBS suppressed subthalamic and cortical-subthalamic coherences in the beta band, correlating with motor improvements. Our results support the desynchronizing mechanism of CR DBS and propose potential biomarkers for closed-loop CR DBS.

Motor improvement and spasms recovery with high-frequency 10kHz spinal cord stimulation in a patient with spastic tetraparesis: beyond pain relief.

To describe the clinical outcomes beyond pain relief of high-frequency spinal cord stimulation at 10kHz (10kHz SCS) in a patient with cervical myelopathy and drug-resistant chronic neuropathic pain with spastic tetraparesis. A patient with C3-C6 myelomalacia and spastic tetraparesis previously treated with decompressive laminectomy underwent implantation of 10kHz SCS for pain management through a trial procedure followed by permanent implantation. Due to the presence of epidural fibrotic scar tissue in the area of the previous C3-C6 laminectomy, the leads could not be implanted at the cervical level; therefore, the leads were positioned at the thoracic level. Data were collected during routine follow-up visits up to 15 months after implantation. Since the trialing phase and during all follow-up visits, along with complete pain relief in the lower limbs, a recovery from spasms was observed with an improvement in motor function. The patient recovered from a sensation of stiffness and difficulty in movement, with a significant decrease in muscle tone, regaining confidence in walking, and no longer needing assistance even for long walking distances. Although all disabling and painful symptomatology in the upper limbs instead did not ameliorate, the Oswestry Disability Index (ODI) score decreased from 50% at baseline to 6%. To our knowledge, recovery from spasms and motor improvement in a spastic tetraparesis patient has never been reported before with 10kHz SCS and possibly this new stimulation paradigm may overcome some performance limitations of traditional low-frequency SCS (LF-SCS). Treatment eliminated spasms at the lower limbs but not at the upper ones, thus suggesting that the location of the epidural leads could affect outcomes.

Bladder Responses to Thoracolumbar Epidural Stimulation in Female Urethane-Anesthetized Rats with Graded Contusion Spinal Cord Injuries.

Spinal cord epidural stimulation (scES) is a therapeutic option that promotes functional improvements in sensory, motor, and autonomic functions following spinal cord injury (SCI). Previous scES mapping studies targeting the lower urinary tract (LUT) in rats demonstrated functional response variability based upon lumbosacral level, parameters used, extent of injury (spinally intact vs. chronic anatomically complete spinal transections), and sex. In the current study, female rats with clinically relevant graded incomplete T9 contusion injuries were mapped with scES at 60 days post-injury at three spinal levels (T13, L3, L6) with a novel miniature 15-electrode array designed to deliver optimal specificity. The results obtained during bladder fill and void cycles conducted under urethane anesthesia indicate frequency dependent sub-motor threshold effects on LUT function with a single row of electrodes positioned across the full medio-lateral extent of the dorsal cord. The findings of improved storage and emptying, represented by significantly longer inter-contractile intervals with T13 scES and L3 scES and by a significantly increased estimated void efficiency with L6 scES, respectively, are consistent with previous studies using intact and chronic complete transected male and female rats. The data support the efficacy of selective spinal network stimulation to drive functionally relevant networks for storage versus emptying phases of the urinary cycle. The current findings further demonstrate the translational promise of scES for SCI individuals with LUT dysfunctions, regardless of injury severity.

Brain tumor patient perceptions toward repetitive transcranial magnetic stimulation for rehabilitation after surgery

Abstract Background Repetitive transcranial magnetic stimulation (rTMS) is established for depression and rehabilitation after stroke and is emerging for cognitive rehabilitation. We sought to evaluate patient and carer perceptions toward rTMS for rehabilitation after neurosurgery. Methods Two surveys were undertaken. Group 1: Patients who received 7 days of rTMS for motor or language rehabilitation for severe postoperative deficits following lesional resection were prospectively surveyed on the last day of their rTMS treatment, as well as their next of kin. Group 2: Patients who had previously been diagnosed with glioma but did not receive rTMS were retrospectively surveyed through two brain tumor charities, including next of kin. Results Group 1: Twenty-one responses. Eleven patients, 10 next of kin. The commonest pathology was WHO Grade 4 glioma (n = 3). Group 2: 24 responses. Sixteen patients, 8 next of kin. The commonest pathology was WHO Grade 2 glioma (n = 7). Most Group 1 respondents reported a positive experience of rTMS (15/21). Patients experienced subjective improvements in gross motor functions of arm and leg weakness and purposeful movement (9/11). Lack of subjective motor improvement was associated with adverse symptoms (e.g., headaches; p = .01). Group 2 respondents were supportive of rTMS. Key priorities included motor and cognitive rehabilitation. They were accepting of longer and more frequent rTMS sessions than Group 1 (p = .028 and &amp;lt;.001, respectively). Commonest concerns pertained to side effects are seizures and headaches. Conclusions rTMS for rehabilitation was well-tolerated by patients with side effects being commoner in those with no subjective motor improvements. Nontreated patients and their next of kin would find longer and more sessions acceptable but have concerns about potential side effects.

Neuroprotective Effect of Melatonin in a Neonatal Hypoxia-Ischemia Rat Model Is Regulated by the AMPK/mTOR Pathway.

Melatonin has been shown to be neuroprotective in different animal models of neonatal hypoxic-ischemic brain injury. However, its exact molecular mechanism of action remains unknown. Our aim was to prove melatonin's short- and long-term neuroprotection and investigate its role on the AMPK (AMP-activated protein kinase)/mTOR (mammalian target of rapamycin) pathway following neonatal hypoxic-ischemic brain injury. Seven-day-old Wistar rat pups were exposed to hypoxia-ischemia, followed by melatonin or vehicle treatment. Detailed analysis of the AMPK/mTOR/autophagy pathway, short- and long-term neuroprotection, myelination, and oligodendrogenesis was performed at different time points. At 7 days after hypoxia-ischemia, melatonin-treated animals showed a significant decrease in tissue loss, increased oligodendrogenesis, and myelination. Long-term neurobehavioral results showed significant motor improvement following melatonin treatment. Molecular pathway analysis showed a decrease in the AMPK expression, with a significant increase at mTOR's downstream substrates, and a significant decrease at the autophagy marker levels in the melatonin group compared with the vehicle group. Melatonin treatment reduced brain area loss and promoted oligodendrogenesis with a clear improvement of motor function. We found that melatonin associated neuroprotection is regulated via the AMPK/mTOR/autophagy pathway. Considering the beneficial effects of melatonin and the results of our study, melatonin seems to be an optimal candidate for the treatment of newborns with hypoxic-ischemic brain injury in high- as well as in low- and middle-income countries.

Effects of high-definition tDCS targeting individual motor hotspot with EMG-driven robotic hand training on upper extremity motor function: a pilot randomized controlled trial

BackgroundDelivering HD-tDCS on individual motor hotspot with optimal electric fields could overcome challenges of stroke heterogeneity, potentially facilitating neural activation and improving motor function for stroke survivors. However, the intervention effect of this personalized HD-tDCS has not been explored on post-stroke motor recovery. In this study, we aim to evaluate whether targeting individual motor hotspot with HD-tDCS followed by EMG-driven robotic hand training could further facilitate the upper extremity motor function for chronic stroke survivors.MethodsIn this pilot randomized controlled trial, eighteen chronic stroke survivors were randomly allocated into two groups. The HDtDCS-group (n = 8) received personalized HD-tDCS using task-based fMRI to guide the stimulation on individual motor hotspot. The Sham-group (n = 10) received only sham stimulation. Both groups underwent 20 sessions of training, each session began with 20 min of HD-tDCS and was then followed by 60 min of robotic hand training. Clinical scales (Fugl-meyer Upper Extremity scale, FMAUE; Modified Ashworth Scale, MAS), and neuroimaging modalities (fMRI and EEG-EMG) were conducted before, after intervention, and at 6-month follow-up. Two-way repeated measures analysis of variance was used to compare the training effect between HDtDCS- and Sham-group.ResultsHDtDCS-group demonstrated significantly better motor improvement than the Sham-group in terms of greater changes of FMAUE scores (F = 6.5, P = 0.004) and MASf (F = 3.6, P = 0.038) immediately and 6 months after the 20-session intervention. The task-based fMRI activation significantly shifted to the ipsilesional motor area in the HDtDCS-group, and this activation pattern increasingly concentrated on the motor hotspot being stimulated 6 months after training within the HDtDCS-group, whereas the increased activation is not sustainable in the Sham-group. The neuroimaging results indicate that neural plastic changes of the HDtDCS-group were guided specifically and sustained as an add-on effect of the stimulation.ConclusionsStimulating the individual motor hotspot before robotic hand training could further enhance brain activation in motor-related regions that promote better motor recovery for chronic stroke.Trial registrationThis study was retrospectively registered in ClinicalTrials.gov (ID NCT05638464).

Cognitive and motor improvement by tummy time practice in preemies from low-income settings: a randomized clinical trial.

Early intervention and parental education for preemies are limited in some low-income countries. Thus, this study aimed to assess whether daily tummy time (TT) associated with usual care (UC) enhances motor and cognitive development in preemies from low-income countries. The main and secondary aim was to assess prone head elevation (PHE) and motor and cognitive functions, respectively. Thirty-one preemies with a mean gestational age at birth of 33.3 ± 1.6 weeks and weighing <2,500 g were included and 18 completed all assessments. Parents from the TT group were asked to perform TT with their preemies for at least 20 min during daily activities and playtime. Motor and cognitive functions were assessed by a blinded examiner using the motor and cognitive composite scores of Bayley-III after two and four months of corrected age. PHE was given by the angle from the tragus of the ear to the supporting surface of the infant; measurements were obtained using the Kinovea® software at baseline, after two, three, and four months of corrected age. The Bayley-III motor composite score of the TT group was higher than the UC group after two and four months of corrected age. The PHE angle increased over time but did not differ between groups. Nevertheless, TT expanded the perspective of preemies to explore their bodies and environment, favoring the stimuli for motor and cognitive patterns. The loss of participants (31%) was one of the limitations of the study, illustrating the challenge of providing continued early interventions to preemies from low-income countries. In this sense, TT practice is a home intervention that may improve motor and cognitive function of preemies immediately after hospital discharge.

Unilateral Magnetic Resonance-Guided Focused Ultrasound Lesion of the Subthalamic Nucleus in Parkinson's Disease: A Prospective Study.

Unilateral subthalamic nucleus (STN) ablation using magnetic resonance-guided focused ultrasound (MRgFUS) is being explored as a new treatment for asymmetric Parkinson's disease (PD). The aims were to study the efficacy and safety of this treatment in asymmetric PD patients and to characterize the lesions. This prospective, single-center, open-label study evaluated asymmetric PD patients at 6 (n = 20) and 12 months (n = 12) after MRgFUS lesion of the STN. The primary outcome was the change in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, Part III (MDS-UPDRS III), score in off medication on the treated side and the adverse events (AEs) at 6-month follow-up. We also evaluated cognitive-neuropsychological changes, self-assessment of clinical improvement, and the correlation of the lesion volume with the motor outcomes. On the treated side, the MDS-UPDRS III score (mean difference = 13.8) and the scores in rigidity, bradykinesia, and tremor improved (P < 0.001) throughout the follow-up compared to baseline (at 6 months: rigidity mean difference = 2.8, improvement: 83.5%; bradykinesia mean difference = 6.0, improvement: 69.4%; tremor mean difference = 4.7, improvement: 91.5%). One patient had severe weakness in the treated hemibody, 1 had moderate dyskinesia, and 1 was in moderate confusional state that became mild (weakness) or completely resolved (dyskinesia and confusional state) at 6 months. The rest of the AEs were mild. We observed no clinically relevant changes in cognitive-neuropsychological tests. The percentage of ablation of the STN correlated with the improvement in the total MDS-UPDRS III and contralateral tremor scores (P < 0.05). Unilateral MRgFUS lesion of the STN resulted in a significant motor improvement. We observed no persistent severe AEs, although mild, mostly transient AEs were frequent. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Effectiveness of Transcranial Direct Current Stimulation (tDCS) during a Virtual Reality Task in Women with Fibromyalgia-A Randomized Clinical Study.

Fibromyalgia (FM) is a chronic condition characterized by widespread musculoskeletal pain, fatigue, and impaired motor performance. This study aimed to investigate the effects of transcranial direct current stimulation (tDCS) during virtual reality (VR) tasks on the motor performance of women with FM. Participants were divided into two groups: Group A received active tDCS for 10 days followed by sham tDCS for 10 days, while Group B received the opposite sequence. Both groups performed VR tasks using MoveHero software (v. 2.4) during the tDCS sessions. Motor performance was assessed by the number of hits (movement with correct timing to reach the targets) and absolute (accuracy measure) and variable (precision measure) errors during VR tasks. Participants were 21 women, aged 30-50 years, and diagnosed with FM. Group A, which received active tDCS first, presented significant improvements in motor performance (number of hits and absolute and variable errors). The benefits of active tDCS persisted into the sham phase, suggesting a lasting neuroplastic effect. tDCS during VR tasks significantly improved motor performance in women with FM, particularly in complex, extensive movements. These findings indicate that tDCS enhances neuroplasticity, leading to sustained motor improvements, making it a promising therapeutic tool in FM rehabilitation.

Cognitive phenotyping of GBA1-Parkinson's disease: A study on deep brain stimulation outcomes

BackgroundHeterozygous variants in the glucocerebrosidase (GBA1) gene are the most common genetic risk factor for Parkinson's Disease (PD). GBA1-PD patients exhibit earlier disease onset, severe motor impairment, and heightened cognitive decline. Deep Brain Stimulation (DBS) offers motor improvement for PD patients, but its cognitive effects, particularly in GBA1-PD, are debated. MethodsThis study involved 96 PD patients who underwent subthalamic nucleus DBS at Hospital de la Santa Creu i Sant Pau between 2004 and 2023. Clinical and neuropsychological assessments were conducted pre- and post-surgery, focusing on Mattis Dementia Rating Scale (MDRS) and Frontal Systems Behavior Scale (FrSBe). Patients were categorized into GBA1-PD and non-GBA1-PD groups, with non-GBA1-PD further divided into cognitive fast-progressors and slow-progressors. ResultsGBA1 variants were present in 13.5 % of patients. GBA1-PD patients showed greater cognitive decline over time, particularly in attention, conceptualization, and memory, compared to non-GBA1-PD. Non-GBA1-PD fast-progressors exhibited significant cognitive deterioration in initiation and conceptualization within the first year post-DBS. Motor outcomes improved similarly across all groups, but slow-progressors showed a greater reduction in Levodopa Equivalent Daily Dose (LEDD). ConclusionsGBA1-PD patients experience more rapid cognitive decline, particularly in posterior-cortical and fronto-striatal functions. Additionally, a subset of non-GBA1-PD patients shows significant early cognitive decline post-DBS, especially in executive functions. Baseline MDRS scores do not predict cognitive outcomes, highlighting the need for further research to refine prognostic tools. Despite cognitive challenges, GBA1-PD patients benefit from DBS in terms of motor outcomes, underscoring the importance of individualized assessments for DBS suitability, regardless of genetic status.

Pediatric peri-insular hemispherotomy and functional hemispherectomy for severe medically refractory epilepsy: comparison of two techniques

PurposeSince it was first described in the 1970s, functional hemispherotomy has been an essential tool in treating disabling, medically refractory epilepsy resulting from diffuse unilateral hemispheric disease. We report our experience with 23 patients who underwent hemispherotomy, both using the functional hemispherotomy (FH) as well as a modified peri-insular hemispherotomy (PIH) technique. We present the surgical technique for the latter, review outcomes following disconnection surgery and discuss the differences between the techniques when it comes to complications and postoperative results. MethodsA retrospective study of 23 patients with refractory seizures who underwent cerebral hemispherectomy. A thorough analysis of the clinical, imaging, surgical features and postoperative results was performed. We also present the surgical technique for a modified PIH technique. ResultsBetween 2000 and 2020, 23 pediatric patients with refractory seizures underwent hemispherotomy (12 FHs, 11 modified PIHs). 91.3% of patients were seizure free at 6 months, 87% at 1 year, and 78.3% at last follow-up. None of the 23 patients presented Engel IV outcome. FH was found to have statistically longer surgical duration (5 ± 1.5 vs. 3.83 ± 0.5 h; p = <0.001). Neurocognition was improved in two thirds of the patients (66.9%). Our study also shows improvement of motor activity in the majority of the patients, regardless of the pathology and surgical technique. In the present report we modified the Cook et al. technique by implementing an amygdalohippocampectomy with resection of the tail of the hippocampus posteriorly and medially, to achieve temporo-occipital disconnection, instead of a complete temporal lobectomy. ConclusionWhen patients are wisely selected, the hemispherectomy procedure should be considered as a most attractive and curative treatment for children with refractory seizures, not only giving the patient a high chance of seizure freedom but also providing an improvement in motor and cognitive skills. In our particular case and based on the present study, the modified PIH proves to be a highly effective technique. It not only has a shorter surgical time but also a very low complication rate.

Utilization of condoliase therapy versus surgery for lumbar disc herniation and comparison of post-treatment motor improvement

Study DesignDouble-center retrospective study. PurposeUtilization trends in interventional treatment for lumbar disc herniation (LDH) have not yet been examined. Furthermore, limited information is currently available on motor recovery with condoliase therapy. Therefore, the present study investigated utilization trends in treatment for LDH and the effects of condoliase therapy on muscle weakness. MethodsThis retrospective, double-center study involved patients with leg pain caused by LDH who received interventional treatment between September 2017 and August 2022. LDH patients were divided into two groups: an operative treatment group and condoliase therapy group. The period between September 2017 and August 2022 was divided into 5 equal parts and changes in the percentage of intervention treatment were examined. Motor recovery was also assessed in the two groups. Patients receiving condoliase therapy were divided into two groups: an effective group and non-effective group. Sex, age, the body mass index, duration of symptoms, herniation level, neurological and radiographic findings, a visual analog scale for leg pain, and the Oswestry disability index were examined in the two groups. ResultsSubjects included 226 males and 115 females with a mean age of 49.2 years, mean BMI of 22.8, and mean duration of symptoms of 5.0 months. The utilization of condoliase therapy for LDH surpassed surgery in the third year after its introduction. In the fourth year, condoliase therapy became the main treatment for LDH. Lower limb muscle strength improved in 76 % of cases receiving condoliase therapy. ConclusionsCondoliase therapy has become an intermediate treatment before surgery in our institutions. Motor recovery in patients receiving condoliase therapy was not inferior to that after surgery; however, in cases with severe muscle weakness with manual muscle test ≤3, the improvement rate was approximately 60 %. These results will be useful for clinicians when providing informed consent and selecting condoliase therapy.