Skin innervation across amyotrophic lateral sclerosis clinical stages: new prognostic biomarkers.

Over recent decades, peripheral sensory abnormalities, including the evidence of cutaneous denervation, have been reported among the non-motor manifestations in amyotrophic lateral sclerosis (ALS). However, a correlation between cutaneous innervation and clinical features has not been found. The aims of this study were to assess sensory involvement by applying a morpho-functional approach to a large population of ALS patients stratified according to King's stages and correlate these findings with the severity and prognosis of the disease. We recruited 149 ALS patients and 41 healthy controls. Patients undertook clinical questionnaires for small fibre neuropathy symptoms (Small Fiber Neuropathy Symptoms Inventory Questionnaire) and underwent nerve conductions studies (NCS) and 3-mm punch skin biopsies from leg, thigh and fingertip. We assessed intraepidermal nerve fibre (IENF) and Meissner corpuscle (MC) density by applying an indirect immunofluorescence technique. Moreover, a subset of 65 ALS patients underwent a longitudinal study with repeat biopsies from the thigh at 6- and 12-month follow-ups. Serum NfL levels were measured in 40 patients. Sensory symptoms and sensory NCS abnormalities were present in 32.2% and 24% of patients, respectively, and increased across clinical stages. Analogously, we observed a progressive reduction in amplitude of the sensory and motor ulnar nerve potential from stage 1 to stage 4. Skin biopsy showed a significant loss of IENFs and MCs in ALS compared with healthy controls (all P < 0.001). Across the clinical stages, we found a progressive reduction in MCs (P = 0.004) and an increase in IENFs (all P < 0.027). The increase in IENFs was confirmed by the longitudinal study. Interestingly, the MC density inversely correlated with NfL level (r = -0.424, P = 0.012), and survival analysis revealed that low MC density, higher NfL levels and increasing IENF density over time were associated with a poorer prognosis (all P < 0.024). To summarize, in patients with ALS, peripheral sensory involvement worsens in parallel with motor disability. Furthermore, the correlation between skin innervation and disease activity may suggest the use of skin innervation as a putative prognostic biomarker.

Preserved striatal innervation maintains motor function despite severe loss of nigral dopaminergic neurons.

Degeneration of dopaminergic neurons in the substantia nigra and their striatal axon terminals causes cardinal motor symptoms of Parkinson's disease. In idiopathic cases, high levels of mitochondrial DNA alterations leading to mitochondrial dysfunction are a central feature of these vulnerable neurons. Here we present a mouse model expressing the K320E-variant of the mitochondrial helicase Twinkle in dopaminergic neurons, leading to accelerated mitochondrial DNA mutations. These K320E-TwinkleDaN mice showed normal motor function at 20 months of age, although ∼70% of nigral dopaminergic neurons had perished. Remaining neurons still preserved ∼75% of axon terminals in the dorsal striatum and enabled normal dopamine release. Transcriptome analysis and viral tracing confirmed compensatory axonal sprouting of the surviving neurons. We conclude that a small population of substantia nigra dopaminergic neurons is able to adapt to the accumulation of mitochondrial DNA mutations and maintain motor control.

The role of orexin in Parkinson's disease.

Emerging evidence has implicated the orexin system in non-motor pathogenesis of Parkinson's disease. It has also been suggested the orexin system is involved in the modulation of motor control, further implicating the orexin system in Parkinson's disease. Parkinson's disease is the second most common neurodegenerative disease with millions of people suffering worldwide with motor and non-motor symptoms, significantly affecting their quality of life. Treatments are based solely on symptomatic management and no cure currently exists. The orexin system has the potential to be a treatment target in Parkinson's disease, particularly in the non-motor stage. In this review, the most current evidence on the orexin system in Parkinson's disease and its potential role in motor and non-motor symptoms of the disease is summarized. This review begins with a brief overview of Parkinson's disease, animal models of the disease, and the orexin system. This leads into discussion of the possible roles of orexin neurons in Parkinson's disease and levels of orexin in the cerebral spinal fluid and plasma in Parkinson's disease and animal models of the disease. The role of orexin is then discussed in relation to symptoms of the disease including motor control, sleep, cognitive impairment, psychological behaviors, and the gastrointestinal system. The neuroprotective effects of orexin are also summarized in preclinical models of the disease.

Long-Term Follow-Up of the LEAP Study: Early Versus Delayed Levodopa in Early Parkinson's Disease.

BACKGROUND AND OBJECTIVE: The Levodopa in EArly Parkinson's disease study showed no effect of earlier versus later levodopa initiation on Parkinson's disease (PD) progression over 80 weeks. We now report the effects over 5 years. METHODS: The Levodopa in EArly Parkinson's disease study randomly assigned patients to levodopa/carbidopa 300/75 mg daily for 80 weeks (early start) or to placebo for 40 weeks followed by levodopa/carbidopa 300/75 mg daily for 40 weeks (delayed start). Follow-up visits were performed 3 and 5 years after baseline. We assessed the between-group differences in terms of square root transformed total Unified Parkinson's Disease Rating Scale score at 3 and 5 years with linear regression. We compared the prevalence of dyskinesia, prevalence of wearing off, and the levodopa equivalent daily dose. RESULTS: A total of 321 patients completed the 5-year visit. The adjusted square root transformed total Unified Parkinson's Disease Rating Scale did not differ between treatment groups at 3 (estimated difference, 0.17; standard error, 0.13; P = 0.18) and 5 years (estimated difference, 0.24; standard error, 0.13; P = 0.07). At 5 years, 46 of 160 patients in the early-start group and 62 of 161 patients in the delayed-start group experienced dyskinesia (P = 0.06). The prevalence of wearing off and the levodopa equivalent daily dose were not significantly different between groups. CONCLUSIONS: We did not find a difference in disease progression or in prevalence of motor complications between patients with early PD starting treatment with a low dose of levodopa 40 weeks earlier versus 40 weeks later over the subsequent 5 years. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A Systematic Review of the Spectrum and Prevalence of Non-motor Symptoms in Multiple System Atrophy.

BACKGROUND: Patients with Multiple System Atrophy (MSA) frequently report non-motor symptoms, and several research groups have highlighted this. OBJECTIVE: We systematically searched for and reviewed papers assessing prevalence of non-motor symptoms (NMS) in MSA patients as reported in the scientific literature. METHODS: We performed a systematic review of studies of subjects with MSA (involving > 10 patients) who were assessed for NMS, published in the English literature in PUBMED and EMBASE databases from 1947-2022. RESULTS: 23 research papers, with data from 2648 clinically diagnosed and 171 pathologically verified cases of MSA were included, along with 238 controls. Mean age for MSA cases was 61.3 (9.2) years, mean disease duration 3.6 (2.7) years. 57.9% were male. Our analysis showed that the prevalence of cognitive issues in MSA varied widely (between 15-100%); dementia per se was uncommon, but assessment in advanced stages of MSA is impacted by unintelligible speech (which may be noted in a quarter of cases). The prevalence of depressive symptoms in MSA was between 44-88%. Sleep disturbances were reported by 17-89%, with REM-sleep behaviour disorder (RBD) rates as high as 75%. Pain was reported by 40-47% of patients: rheumatic or musculoskeletal sources of pain being commonest. Fatigue was reported by 29-60% of patients. Symptoms of autonomic failure in MSA were seen in 34-96.5% patients at baseline. CONCLUSION: In routine clinical practice, NMS in MSA are under-recognised by clinicians. These impact hugely on patient quality of life and contribute to their overall morbidity. A methodical ascertainment of these complaints will address an unmet need, and lead to a more holistic approach of care for individuals with MSA.

Association between autonomic dysfunction with motor and non-motor symptoms in patients with Parkinson's disease.

To investigate the association between autonomic dysfunction (AutD) and motor as well as non-motor symptoms (NMS) in patients with Parkinson's disease (PD). Fifty-three PD patients were divided into two groups based on the number of domains affected by AutD: a multi-domain AutD group (AutD-M) and a single-domain AutD group (AutD-S), as evaluated using the Scale for Outcomes in Parkinson's disease-Autonomic (SCOPA-AUT), which assesses autonomic symptoms, one of the NMS. A comprehensive comparison was conducted between the two groups, including clinical measures such as clinical scales, quantitative evaluations of motor function and exercise capacity. Spearman correlation analysis was employed to investigate the relationship between AutD severity and PD symptoms. Additionally, we performed multiple linear regression model analysis to determine whether associations between SCOPA-AUT scores and clinical assessments remained significant after adjusting for Hoehn and Yahr stage, sex, and age. PD patients in the AutD-M group exhibited significantly more severe NMS and motor symptoms compared to those in the AutD-S group. In correlation analysis, SCOPA-AUT scores showed significant correlations with multiple clinical symptoms, such as most of the NMS, 10-MWT and CPET parameters. Furthermore, regression analysis also revealed that more pronounced fatigue, anxiety, depressive symptoms, worse walking speed and impaired exercise capacity were associated with higher SCOPA-AUT scores. The presence of AutD is correlated with emotional disturbances, decreased exercise endurance, and impaired gait function in patients with PD. Early management of AutD may prove beneficial in alleviating some NMS and motor symptoms in PD.

Motor cortex transcranial direct current stimulation improves non-motor symptoms in early-onset Parkinson's disease: a pilot study.

Early-onset Parkinson's Disease (EOPD) demands tailored treatments. The younger age of patients might account for a higher sensitivity to transcranial direct current stimulation (tDCS) based non-invasive neuromodulation, which may raise as an integrative therapy in the field. Accordingly, here we assessed the safety and efficacy of the primary left motor cortex (M1) anodal tDCS in EOPD. Ten idiopathic EOPD patients received tDCS at 2.0 mA per 20 min for 10 days within a crossover, double-blind, sham-controlled pilot study. The outcome was evaluated by measuring changes in MDS-UPDRS part III, Non-Motor Symptoms Scale (NMSS), PD-cognitive rating scale, and PD Quality of Life Questionnaire-39 scores. We showed that anodal but not sham tDCS significantly reduced the NMSS total and "item 2" (sleep/fatigue) scores. Other parameters were not modified. No adverse events occurred. M1 anodal tDCS might thus evoke plasticity changes in cortical-subcortical circuits involved in non-motor functions, supporting the value as a therapeutic option in EOPD.

Subthalamic nucleus deep brain stimulation in primary Meige syndrome: motor and non-motor outcomes.

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) has emerged as a promising treatment for movement disorders. This prospective study aims to evaluate the effects of bilateral subthalamic nucleus DBS (STN-DBS) on motor and non-motor symptoms in patients with primary Meige syndrome. METHODS: Thirty patients who underwent bilateral STN-DBS between April 2017 and June 2020 were included. Standardized and validated scales were utilized to assess the severity of dystonia, health-related quality of life, sleep, cognitive function and mental status at baseline and at 1 year and 3 years after neurostimulation. RESULTS: The Burke-Fahn-Marsden Dystonia Rating Scale movement scores showed a mean improvement of 63.0% and 66.8% at 1 year and 3 years, respectively, after neurostimulation. Similarly, the Burke-Fahn-Marsden Dystonia Rating Scale disability scores improved by 60.8% and 63.3% at the same time points. Postoperative quality of life demonstrated a significant and sustained improvement throughout the follow-up period. However, cognitive function, mental status, sleep quality and other neuropsychological functions did not change after 3 years of neurostimulation. Eight adverse events occurred in six patients, but no deaths or permanent sequelae were reported. CONCLUSIONS: Bilateral STN-DBS is a safe and effective alternative treatment for primary Meige syndrome, leading to improvements in motor function and quality of life. Nevertheless, it did not yield significant amelioration in cognitive, mental, sleep status and other neuropsychological functions after 3 years of neurostimulation.

Taste disorders and alopecia in myasthenia gravis.

BACKGROUND: Non-motor symptoms in myasthenia gravis (MG) are rarely confirmed. Although there are some small cohort studies, a large-systemic survey has not yet been performed. METHODS: We investigated the incidence and clinical characteristics of patients with MG who had taste disorders and alopecia using data of 1710 patients with MG enrolled in the Japan MG Registry 2021. RESULTS: Among them, 104 (6.1%) out of 1692 patients and 138 (8.2%) out of 1688 patients had histories of taste disorders and alopecia, respectively. Among the patients with MG, taste disorders were significantly more common in women, those with severe symptoms, refractory MG, or thymoma-associated MG, and were less common in those with ocular MG. The taste disorders often occurred after the onset of MG and often responded to MG treatments. Alopecia was more common in MG patients with a history of bulbar palsy and thymoma, and it often occurred before the onset of MG and sometimes responded to MG treatments. Multivariate logistic regression analysis revealed taste disturbance was associated with worst quantitative MG score and thymoma-associated MG; and alopecia was associated with thymoma-associated MG. CONCLUSION: Clinicians should be aware of the non-motor symptoms in MG, especially in patients with severe myasthenic symptoms and thymoma-associated MG.

Cognitive, Emotional, and Other Non-motor Symptoms of Spinocerebellar Ataxias.

PURPOSE OF REVIEW: Spinocerebellar ataxias (SCAs) are autosomal dominant degenerative syndromes that present with ataxia and brain stem abnormalities. This review describes the cognitive and behavioral symptoms of SCAs in the context of recent knowledge of the role of the cerebellum in higher intellectual function. RECENT FINDINGS: Recent studies suggest that patients with spinocerebellar ataxia can display cognitive deficits even early in the disease. These have been given the term cerebellar cognitive affective syndrome (CCAS). CCAS can be tracked using newly developed rating scales. In addition, patients with spinocerebellar ataxia also display impulsive and compulsive behavior, depression, anxiety, fatigue, and sleep disturbances. This review stresses the importance of recognizing non-motor symptoms in SCAs. There is a pressing need for novel therapeutic interventions to address these symptoms given their deleterious impact on patients' quality of life.

Impact of Non-Motor Symptoms on Quality of Life in Patients with Early-Onset Parkinson's Disease.

BACKGROUND: Early-onset Parkinson's disease (EOPD) refers to patients with Parkinson's disease (PD) whose age at disease onset is less than 50 years. Literature on the non-motor symptoms (NMS) in these patients is very limited in the Indian context. We aimed to study the NMS in patients with EOPD and its impact on the quality of life (QoL). METHODS: We included 124 patients with EOPD with a mean age at disease onset between 21 and 45 years and 60 healthy controls (HC). NMS were assessed using validated scales, and the QoL domains were evaluated using the PD QoL-39 scale (PDQ-39). RESULTS: The mean age at disease onset in EOPD patients was 37.33 ± 6.36 years. Majority of the patients were male (66.12%). The average disease duration was 6.62 ± 5.3 years. EOPD patients exhibited a significantly higher number of NMS per patient (7.97 ± 4.69) compared to HC (1.3 ± 1.39; p < 0.001). The most common NMS reported were urinary dysfunction, body pain, poor sleep quality, constipation, anxiety, depression, cognitive impairment, and REM sleep behavior disorder. The total NMS burden correlated with the QoL measures. Distinctive patterns of QoL subdomain involvement were identified, with sleep/fatigue, mood/cognition, and urinary dysfunction independently influencing QoL metrics. CONCLUSIONS: Our study provides valuable insights into the NMS profile and its impact on QoL in patients with EOPD, addressing an important knowledge gap in the Indian context. By understanding the specific NMS and their influence on QoL, healthcare professionals can develop targeted interventions to address these symptoms and improve the overall QoL.

Association between motor symptoms of Parkinson's disease and swallowing disorders.

BACKGROUND: Parkinson's disease (PD) presents with motor symptoms that hinder physical activity. This study aimed to thoroughly investigate swallowing dysfunction in patients with PD using videofluoroscopy (VF) and the Movement Disorder Society (MDS)-Unified PD Rating Scale (UPDRS) sub-scores. METHODS: This study was part of an intervention project to evaluate the effectiveness of cervical percutaneous interferential current stimulation in patients with Hoehn and Yahr stages 2-4 PD. Baseline data, including swallowing-related indicators such as VF, were obtained and compared to the MDS-UPDRS sub-scores including rigidity, tremor, postural instability/gait difficulty, and limb scores. RESULTS: Twenty-seven patients were included in this study. In the VF analysis, laryngeal penetration/aspiration, oral cavity residue, epiglottic vallecular residue, and pharyngeal residue were observed with remarkable frequency. The multivariate analysis revealed that the mean rigidity score of UPDRS was an independent and significantly correlated factor with laryngeal penetration/aspiration during the ingestion of 10 mL of water (odds ratio 1.294, 95% confidence interval 1.035-1.617; p = 0.024). CONCLUSION: This study revealed a correlation between muscle rigidity and laryngeal penetration or aspiration risk. The detailed comparative analysis of various individual PD symptoms and swallowing disorders was substantial, which enabled early detection of the risk of swallowing disorder and the implementation of appropriate measures. TRIAL REGISTRATION NUMBER: jRCTs062220013.

Association between fatigue and MDS-UPDRS in individuals with Parkinson's disease: cross-sectional study.

BACKGROUND: Fatigue is significant in the context of Parkinson's disease (PD), considering that one-third of patients classify it as the most restricting symptom in their daily life activities (DLAs). The objective was to verify the relationship (association) between fatigue and non-motor and motor symptoms of PD. METHODS: A cross-sectional study which included 100 individuals with PD. Initially, demographic and clinical data (modified Hoehn and Yahr scale-HY, anxiety, and depression) were collected. To assess the non-motor and motor symptoms of PD, the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) was applied. Fatigue was evaluated using the Parkinson Fatigue Scale. RESULTS: A higher HY score, greater severity of non-motor aspects of DLAs and motor aspects of DLAs, more motor complications, and higher levels of anxiety as well as depression were observed in the "fatigue" group. Fatigue was associated with a lower daily equivalent levodopa dose (LEDD), a higher body mass index (BMI), anxiety, depression, and the presence of non-motor symptoms. CONCLUSION: Non-motor symptoms are more determining factors for fatigue than the motor condition itself, with an association between fatigue and higher BMI scores, increased anxiety and depression, lower LEDD, and greater severity of non-motor aspects of DLAs. Individuals in the "fatigue" group had higher HY scores, anxiety, and depression, worse non-motor and motor symptoms related to experiences of daily life, as well as motor complications.

Prevalence and correlates of fatigue in amyotrophic lateral sclerosis: A systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to determine the frequency and correlates of fatigue in patients with amyotrophic lateral sclerosis (ALS). METHODS: Three databases were searched up to 2nd May 2023 to identify studies reporting fatigue frequency in ALS. Studies included had to identify ALS patients through one of ALS diagnostic criteria and measure fatigue by a validated tool with a specific cut-off value. Meta-analysis was conducted using RStudio's "meta" package with a random-effects model. Subgroup analyses and meta-regression explored the relationship between fatigue frequency in ALS and different covariates. RESULTS: Eleven studies, compromising 1072 patients, met the inclusion criteria and were included in our analysis. The pooled frequency of fatigue across all studies was 48% (95% CI = 40% to 57%). Our subgroup analysis based on the ALSFRS-R revealed a higher frequency of fatigue in studies with lower scores (< 30) compared to those with higher scores (≥ 30), with a pooled frequency of 62% (95% CI = 43% to 79%) and 43% (95% CI = 37% to 49%), respectively. Also, the meta-regression analysis showed a significant negative association between fatigue and ALSFRS-R mean (P = 0.02). The included studies reported an association between fatigue and lower functional status and poorer quality of life in patients with ALS. CONCLUSION: Our findings suggest that fatigue is prevalent in almost half of ALS patients and is associated with lower functional status and poorer quality of life, highlighting the importance of assessing and managing fatigue in ALS patients.

Hearing dysfunction heralds an increase in non-motor burden and a worse quality of life in Parkinson's disease: new insights from non-motor spectrum.

BACKGROUND: Sensorial non-motor symptoms (NMSs) in Parkinson's disease (PD) still lack appropriate investigation in clinical practice. This study aimed to assess if and to what extent auditory dysfunction is associated with other NMSs in PD and its impact on patient's quality of life (QoL). METHODS: We selected patients with idiopathic PD, without other concomitant neurological diseases, dementia, or diagnosis of any audiological/vestibular disease. Demographic and clinical data were collected. Patients underwent otoscopic examination, audiological testing with pure tone audiometry (PTA) and distortion product otoacoustic emissions (DPOAEs) and completed Non-Motor Symptoms Scale (NMSS) and Parkinson's Disease Questionnaires-39 (PDQ-39). ANCOVA and partial correlation analysis have been used for statistical analysis. RESULTS: 60 patients were enrolled and completed PTA and DPOAEs. 32 patients with hearing impairment (HI), assessed by PTA, (hearing threshold ≥ 25 dB) showed similar disease duration, motor impairment, and staging, compared to patients without HI, but higher scores both in NMSS and in PDQ-39, except for cardiovascular (CV), gastrointestinal (GI), urogenital (U) and sexual function (SF) of NMSS. In addition, DPOAEs showed a significant correlation with higher scores both in NMSS and PDQ-39, except for CV, SF, GI, U and perceptual problem subdomains of NMSS. CONCLUSION: This study demonstrated that PD patients with HI have a greater burden of NMS and lower related QoL and functioning. Our results highlight the importance to reconsider HI as a NMS, in parallel with the others. HI evaluation, even in asymptomatic patients, may reveal a wider pathology with a worse QoL.

Emotional atypical arousal ratings for unpleasant stimuli in patients with Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, including alteration in emotional processing and recognition of emotions. We explored the effects of PD on the emotional behavioral ratings using a battery of affective visual stimuli selected from the International Affective Picture System (IAPS). METHODS: Twenty-two patients diagnosed with idiopathic PD and 22 healthy controls (HC), matched by age, gender, and education, were enrolled in the study. Following a clinical assessment, each participant was asked to evaluate the arousal and valence of affective visual stimuli, and response time was recorded. Disease-specific measures including the MDS Unified Parkinson's Disease Rating Scale (MDS UPDRS) and the Non-Motor Symptom Scale (NMSS) were also collected. RESULTS: PD patients exhibited higher arousal responses compared to HC for negative/unpleasant pictures (scoring 7.32 ± 0.88 vs 5.43 ± 2.06, p < 0.001). The arousal response to negative/unpleasant pictures was correlated with measures of non-motor burden in PD (MDS UPDRS I and NMSS, rho = 0.480 and p = 0.023, rho = 0.533 and p = 0.010, respectively). CONCLUSION: Impaired emotional processing characterizes PD patients with mild disease and is related to the non-motor symptom burden. Given the importance of emotional processing for the development and maintenance of close interpersonal relationship and for coping with specific medical situations, it is crucial to direct PD patients towards therapeutic interventions focused on the recognition and processing of emotions.

Efficacy and safety of acupuncture therapy for neuropsychiatric symptoms among patients with Parkinson's disease: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the efficacy and safety of acupuncture therapy for neuropsychiatric symptoms in patients with Parkinson's disease. METHODS: We searched eight databases from their inception until 14 April 2024, including PubMed, Cochrane Library, Embase, Web of Science, SinoMed, China National Knowledge Infrastructure, China Science and Technology Periodical Database, and Wanfang Database. The search aimed to find randomized controlled trials assessing the effectiveness of acupuncture for neuropsychiatric symptoms in patients with Parkinson's disease. Literature screening and data extraction were performed independently by the authors. Meta-analysis was conducted using RevMan V.5.3 software, and Stata 17.0 software was used for detecting publication bias and performing sensitivity analysis. RESULTS: Twenty-eight studies, involving 2148 participants, met the inclusion criteria. The meta-analysis revealed that acupuncture therapy improved depression-related scale scores (standardized mean difference (SMD) = -0.70, 95%CI [-0.98, -0.42], p < 0.00001), anxiety-related scale scores (SMD = -0.78, 95% CI [-1.43, -0.14], p = 0.02), Montreal Cognitive Assessment scores (weighted mean difference (WMD) = 2.74, 95% CI [2.43, 3.05], p < 0.00001), Mini Mental State Examination scores (WMD = 2.36, 95% CI [0.78, 3.94], p = 0.003), Yale-Brown Obsessive Compulsive Scale scores, and Parkinson's Disease Questionnaire-39 scores (WMD = -2.66, 95% CI [-4.83, -0.49], p = 0.02) compared to controls. CONCLUSION: This review supports the application of acupuncture to reduce the severity of neuropsychiatric symptoms including depression, anxiety, and impulse control disorders, and to improve cognition and quality of life in patients with Parkinson's disease. The adverse effects associated with acupuncture, either alone or as adjunctive therapy, were relatively minor.

Objective clinical registration of tremor, bradykinesia, and rigidity during awake stereotactic neurosurgery: a scoping review.

Tremor, bradykinesia, and rigidity are incapacitating motor symptoms that can be suppressed with stereotactic neurosurgical treatment like deep brain stimulation (DBS) and ablative surgery (e.g., thalamotomy, pallidotomy). Traditionally, clinicians rely on clinical rating scales for intraoperative evaluation of these motor symptoms during awake stereotactic neurosurgery. However, these clinical scales have a relatively high inter-rater variability and rely on experienced raters. Therefore, objective registration (e.g., using movement sensors) is a reasonable extension for intraoperative assessment of tremor, bradykinesia, and rigidity. The main goal of this scoping review is to provide an overview of electronic motor measurements during awake stereotactic neurosurgery. The protocol was based on the PRISMA extension for scoping reviews. After a systematic database search (PubMed, Embase, and Web of Science), articles were screened for relevance. Hundred-and-three articles were subject to detailed screening. Key clinical and technical information was extracted. The inclusion criteria encompassed use of electronic motor measurements during stereotactic neurosurgery performed under local anesthesia. Twenty-three articles were included. These studies had various objectives, including correlating sensor-based outcome measures to clinical scores, identifying optimal DBS electrode positions, and translating clinical assessments to objective assessments. The studies were highly heterogeneous in device choice, sensor location, measurement protocol, design, outcome measures, and data analysis. This review shows that intraoperative quantification of motor symptoms is still limited by variable signal analysis techniques and lacking standardized measurement protocols. However, electronic motor measurements can complement visual evaluations and provide objective confirmation of correct placement of the DBS electrode and/or lesioning. On the long term, this might benefit patient outcomes and provide reliable outcome measures in scientific research.

Sensor-Based Quantification of MDS-UPDRS III Subitems in Parkinson's Disease Using Machine Learning.

Wearable sensors could be beneficial for the continuous quantification of upper limb motor symptoms in people with Parkinson's disease (PD). This work evaluates the use of two inertial measurement units combined with supervised machine learning models to classify and predict a subset of MDS-UPDRS III subitems in PD. We attached the two compact wearable sensors on the dorsal part of each hand of 33 people with PD and 12 controls. Each participant performed six clinical movement tasks in parallel with an assessment of the MDS-UPDRS III. Random forest (RF) models were trained on the sensor data and motor scores. An overall accuracy of 94% was achieved in classifying the movement tasks. When employed for classifying the motor scores, the averaged area under the receiver operating characteristic values ranged from 68% to 92%. Motor scores were additionally predicted using an RF regression model. In a comparative analysis, trained support vector machine models outperformed the RF models for specific tasks. Furthermore, our results surpass the literature in certain cases. The methods developed in this work serve as a base for future studies, where home-based assessments of pharmacological effects on motor function could complement regular clinical assessments.

The effect of home-based exercise on motor and non-motor symptoms with Parkinson's disease patients: A systematic review and network meta-analysis.

OBJECTIVE: To evaluate the effects of home-based exercise in Parkinson's disease (PD) patients. DESIGN: A network meta-analysis of randomized controlled trials. METHODS: This study systematically searched PubMed, MEDLINE, Embase, Cochrane library and Web of Science. The quality of the literature was assessed using the Cochrane Risk of Bias 2.0 criteria. The data were pooled using R software. Results are presented as pooled standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS: Thirty studies involving 2264 PD patients were included. Meta-analysis results showed that home-based exercise had a small effect in relieving overall motor symptoms in PD patients (SMD: -.28, 95% Crl [-.43; -.14]), improving quality of life (SMD = .15 [.03, .26]), walking speed (SMD = .30 [.04, .56]), balance ability (SMD = .18 [.04, .33]; p < .0001) and finger dexterity (SMD = .28 [.10, .46]). Mixed exercise (Mix) had better effects on improving motor symptoms and quality of life. In addition, the results of dose analysis showed that only mixed exercise exceeding 850 METs-min per week and more than 18 weeks can significantly alleviate the overall motor symptoms of PD patients. CONCLUSION: Home-based exercise was an effective form of therapy for alleviating motor symptoms. In addition, Mix appeared to be more suitable for PD patients engaging in home-based exercise. Existing evidence suggested that significant therapeutic effects were achieved with a Mix, with a weekly exercise volume exceeding 850 METs and a duration of more than 18 weeks. RELEVANCE TO CLINICAL PRACTICE: Home-based exercise had a small effect in relieving overall motor symptoms in PD patients, improving quality of life, walking speed, balance ability and finger dexterity. In terms of exercise dosage, we recommend the exercise period is no less than 18 weeks and the dose per is no less than 850 METs-min. No Patient or Public Contribution.