This study examines the efficacy of single photon emission computed tomography/computed tomography (SPECT/CT) guided BoNT-A injections for alleviating motor and non-motor symptoms in cervical dystonia (CD) patients. It also assesses the accuracy of SPECT/CT muscle imaging in identifying responsible muscles and analyzes the quantitative significance of the SUVmax index. A total of 102 patients diagnosed with primary cervical dystonia (CD) were recruited and assessed at baseline, as well as at 2, 4, 8, 12, and 24 weeks post-botulinum toxin A (BoNT-A) injection. Among these patients, 79 underwent SPECT/CT imaging (SPECT/CT group), and 23 did not (control group). Both groups received BoNT-A injections guided by EMG, and their symptom improvements were compared. In the SPECT/CT group, the distribution of responsible muscles and its correlation with clinical phenotypes were analyzed. Furthermore, in a subset of 51 CD patients, overall and mean SUVmax of responsible muscles were quantified, and their correlation with the severity of motor symptoms was analyzed. In both the Tsui and TWSTRS scales, the SPECT/CT group (n = 69) showed significantly higher overall improvement rates compared to the control group (n = 23), with statistically significant differences. In 79 CD patients, SPECT/CT imaging showed that common responsible muscles were the splenius capitis (SPCa), levator scapulae (Lev), splenius cervicis (SPCe), semispinalis capitis (SmCa), obliquus capitis inferior (OCI), and semispinalis cervicis (SSc). The deflection in CD patients was mainly influenced by the ipsilateral SPCa, SPCe, Lev, OCI, longissimus cervicis (LGc), and contralateral sternocleidomastoid muscle (SCM). In 51 CD patients, significant positive correlations were found between overall SUVmax of responsible muscles and motor symptom scores, as well as between the mean SUVmax of responsible muscles and motor symptom scores. SPECT/CT muscle imaging significantly improves motor symptoms in CD patients when used for BoNT-A injections. It effectively identifies responsible muscles, and its SUVmax value serves as an objective indicator of motor symptom severity. SPECT/CT shows promise as a valuable tool for diagnosing and treating CD.

Upper limb spasticity is a common and disabling complication of stroke. Botulinum toxin type A (BoNT-A) is widely used for focal spasticity treatment, but naturally derived products may present limitations related to immunogenicity and manufacturing variability. Recombinant botulinum toxin type A, produced by genetic engineering without complexing proteins, may provide improved product consistency. This Ib/II study evaluated the safety, tolerability, and preliminary efficacy of recombinant botulinum toxin type A in adults with post-stroke upper limb spasticity.This multicenter, seamless Ib/II clinical study included an open-label dose-escalation Ib phase and a randomized, double-blind, placebo-controlled II phase. Adult patients with post-stroke upper limb spasticity received a single intramuscular injection of recombinant botulinum toxin type A or placebo. The primary endpoint in Phase II was the change from baseline in the Modified Ashworth Scale (MAS) score of the primary target muscle group at Week 4. Secondary endpoints included MAS and Tardieu scale changes in individual muscle groups, Disability Assessment Scale (DAS), Physician's Global Assessment (PGA), and immunogenicity.The Ib phase showed improvements in MAS, DAS, and PGA, indicating an early efficacy signal. In Phase II, recombinant botulinum toxin type A produced a significant reduction in MAS score of the primary target muscle group at Week 4 compared with placebo, with effects sustained through Week 12. At Week 4, the PGA score in the Eveotox® group showed a statistically significant improvement compared with the placebo group. While MAS and PGA scores showed significant improvement, DAS functional scores did not differ statistically from the placebo group at week 4. The treatment was generally well tolerated, and low incidence of antibodies were observed.Recombinant botulinum toxin type A was safe and effective in reducing post-stroke upper limb spasticity after a single administration. These results support further Phase III clinical evaluation.

Chronic neuroinflammation is implicated in the pathogenesis of Parkinson's disease (PD), contributing to progressive dopaminergic neuron loss. Cobrotoxin (CoTX), a short-chain α-neurotoxin isolated from Naja atra venom, exerts anti-inflammatory and analgesic effects in several inflammation-related disease models. However, whether CoTX modulates glia-mediated neuroinflammation or confers neuroprotection in PD remains unknown. In this study, we conducted a randomized, placebo-controlled clinical trial and preclinical animal studies to explore the therapeutic efficacy and mechanisms of CoTX in PD. A 12-day subcutaneous regimen of Cobratide (an injectable form of CoTX), consisting of 70 μg daily for 5 days, a 2-day interval, and another 5-day course, significantly improved motor symptoms in PD patients, as reflected by the UPDRS Part II + III scores, with a well-tolerated safety profile. These beneficial effects were further validated in both MPTP- and lipopolysaccharide-induced PD mouse models. Specifically, intranasal administration of CoTX ameliorated motor coordination defects, attenuated dopaminergic neuronal loss, and suppressed glia-mediated neuroinflammation in the substantia nigra of MPTP-challenged mice. Mechanistically, CoTX did not directly protect neurons; instead, it conferred indirect neuroprotection by inhibiting neuroinflammation via blockade of the NF-κB/STAT1 signaling cascades. Furthermore, CoTX functionally interacted with TLR4, which may act as a putative molecular target of CoTX. Collectively, these findings demonstrate the anti-neuroinflammatory and neuroprotective effects of CoTX in PD, highlighting its potential as a promising therapeutic candidate.

BACKGROUND:Depression is a common and early non-motor symptom of Parkinson's disease (PD) with significant sexual dimorphism, yet its underlying molecular mechanisms remain poorly understood. This study aimed to elucidate the sex-specific plasma proteomic profiles of depression in patients with PD (DPD) and to investigate the role of complement-mediated synaptic pruning in its pathophysiology. METHODS:Plasma proteomic analysis was performed on data from the Parkinson's Progression Markers Initiative (PPMI) and an independent validation cohort, stratified by sex. Functional enrichment analyses identified dysregulated pathways. A chronic MPTP/probenecid-induced mouse model of PD was used to validate findings. Behavioural tests assessed motor and depressive-like phenotypes. Proteomic, biochemical, and imaging techniques were used to evaluate protein expression, synapse density, and microglial phagocytosis. The therapeutic mechanism of Botulinum Neurotoxin A (BoNT/A) on DPD was investigated in wild-type, C3-/- and C3aR-/- mice and in microglial cultures. FINDINGS:Proteomic profiling revealed both conserved complement-driven immune dysfunction and profound sex-divergent molecular perturbations underlying PD and DPD. Complement and coagulation cascades were consistently upregulated in both sexes. In MPTP-treated male and female mice, hippocampal complement components (C1Q, C3, C3aR) and downstream signalling (p-STAT3, p-P65) were elevated, accompanied by microglial synapse phagocytosis and depressive-like behaviours. Genetic deletion of C3 rescued both MPTP-induced motor and depressive-like behavioural deficits and prevented hippocampal synaptic loss associated with microglial synaptic engulfment. BoNT/A treatment alleviated depressive-like behaviours and reduced microglial synaptic engulfment in an MPTP model; these therapeutic effects were abolished in C3-/- and C3aR-/- mice. Single-cell RNA sequencing and in vitro phagocytosis assay confirmed that BoNT/A modulated phagocytosis-related microglial subclusters. INTERPRETATION:DPD exhibits distinct sex-specific immune signatures, with convergent complement pathway activation driving microglial synaptic pruning and depressive symptoms. The antidepressant effect of BoNT/A is mediated through inhibition of the C3-C3aR signalling axis. These findings highlight the potential for sex-stratified diagnostics and complement-targeted therapies for depression in patients with PD. A key limitation is that our clinical analyses were constrained by limited validation cohort sizes, and mechanistic studies were limited to male mice, which may restrict the generalisability of our findings to female populations. FUNDING:National Natural Science Foundation of China, Key Project of the Natural Science Foundation of Jiangsu Provincial Higher Education Institutions, Project of Biomedical Basic Research Center (BBRC) of Jiangsu, Clinical Research Center of Neurological Disease in The Second Affiliated Hospital of Soochow University, Project of MOE Key Laboratory of Geriatric Diseases and Immunology, Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases; The Lingang Laboratory fund; Shanghai Science and Technology Innovation Sailing Special Project, and Shanghai Municipal Science and Technology Major Project; Zhejiang Provincial Natural Science Foundation of China.

ABSTRACT Background Visual dysfunction is a common nonmotor manifestation of Parkinson's disease (PD) that may precede motor symptoms. This study aimed to characterize the early preformed fibril (PFF) mouse model of PD. Methods Male C57BL/6J mice received intrastriatal injections of α‐synuclein (α‐syn) PFFs or phosphate‐buffered saline. Visual function was evaluated at 3 and 6 months postinjection using pattern visual evoked potentials (PVEPs) and the visual cliff test. Retinal morphology and protein expression were assessed by hematoxylin–eosin staining, immunofluorescence, and Western blot analysis for phosphorylated α‐syn (pS129), tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), and Iba1. Pathological α‐syn distribution in the visual pathway and association cortices was examined by fluorescence microscopy. Results At 3 months, PFF‐injected mice showed prolonged PVEP latency and reduced amplitude, indicating early visual pathway dysfunction, which worsened by 6 months. Retinal structure was preserved, but p‐α‐syn accumulation appeared in ganglion cells, accompanied by reduced TH expression and activation of microglia and Müller glia. The pSer129‐immunoreactive structures were detected in the visual cortex and visual association cortices, including frontal, parietal, temporal, and amygdaloid regions. Conclusions Functional and pathological alterations in the visual system emerge before motor deficits in α‐syn PFF‐injected mice. Early retinal and cortical synucleinopathy may underlie prodromal visual dysfunction and serve as potential biomarkers for early PD diagnosis.

Social isolation during adolescence is a critical risk factor for negative emotional symptoms, yet its neurobiological mechanisms remain incompletely understood. Here, we integrate human and mouse data to investigate the behavioral, functional, and molecular consequences of social isolation across development. In humans from the Human Connectome Project in Development, reduced social connectedness was robustly associated with greater depressive and anxiety symptoms across adolescence, with sex-specific patterns in effect distribution. At the neural level, social experience was preferentially associated with alterations in hippocampal functional connectivity (FC) rather than gross structure, and exhibited sex- and hemisphere-dependent coupling with large-scale cortical networks. In parallel, adolescent mice exposed to chronic social isolation exhibited marked reductions in hippocampal synaptic density and calcium signaling, accompanied by astrocyte-associated upregulation of complement components C3 and complement factor properdin and enhanced complement-mediated microglial synaptic pruning. Genetic deletion of C3 rescued synaptic deficits and alleviated depressive-like behaviors. Together, these findings identify a conserved neuroimmune pathway through which adolescent social isolation disrupts hippocampal FC, with sex- and species-specific phenotypic expression across behavioral and neural levels, highlighting a sex-specific mechanism linking social experience to neuropsychiatric risk.

Objective: Restless legs syndrome (RLS) is a highly prevalent neurological complication in end-stage renal disease (ESRD) patients. This study aimed to explore the transcranial sonography (TCS) characteristics of the substantia nigra (SN) and brainstem raphe (BR) in ESRD patients with and without RLS and to evaluate the diagnostic value of SN echogenicity for ESRD-related RLS. Methods: A total of 65 ESRD patients (45 with RLS [ESRD + RLS] and 20 without RLS [ESRD - RLS]) from the dialysis center and 30 age- and gender-matched healthy controls (NC) from the health management center were enrolled between January 2017 and December 2022. All participants underwent TCS to measure the bilateral SN echogenic area, and the total SN echogenic area (SNsA) was calculated. BR echogenicity was assessed using a semiquantitative scale. Receiver operating characteristic (ROC) curves were plotted to determine the optimal SNsA cutoff for diagnosing ESRD + RLS. Results: The SNsA in the ESRD + RLS group [0.15 (0.13-0.22) cm2] was significantly smaller than that in the ESRD - RLS group [0.27 (0.23-0.31) cm2] and the NC group [0.27 (0.22-0.30) cm2] (both p < 0.001). ROC curve analysis showed that SNsA had the highest diagnostic efficacy for ESRD + RLS, with an area under the curve (AUROC) of 0.823 (95% confidence interval [CI]: 0.722-0.924). At a cutoff of 0.22 cm2, SNsA yielded a sensitivity of 85.0%, specificity of 73.3%, accuracy of 76.92%, positive predictive value (PPV) of 58.6%, and negative predictive value (NPV) of 91.7%. The prevalence of BR hypoechogenicity was significantly higher in ESRD + RLS (33.33%) and ESRD - RLS (35.00%) groups than in the NC group (10.00%) (both p < 0.05), but no difference was observed between the two ESRD subgroups (p > 0.05). No significant differences in third ventricle (TV) width or bilateral middle cerebral artery peak systolic velocity (MCA-PSV) were found among the three groups (all p > 0.05). Conclusions: ESRD + RLS patients exhibit significant SN hypoechogenicity compared with ESRD - RLS patients and healthy controls. SNsA with a cutoff of 0.22 cm2 serves as a reliable imaging biomarker for diagnosing ESRD + RLS, and TCS is a valuable noninvasive tool to assist clinical decision-making in this population.

Ultra-processed foods (UPFs), widely consumed globally, are increasingly recognised as a key factor in poor dietary quality and diet-related health risks. However, little is known about the role of UPF consumption in the development and progression of Parkinson's disease (PD). We followed 121 440 participants who were free of cancer, PD and dementia at baseline, each completing at least two 24-hour dietary assessments. UPF consumption was defined according to the Nova classification. Eight prodromal features were identified through self-reported diagnoses, hospital admission records and primary care data. Prodromal PD was defined as the presence of ≥3 prodromal PD features. Incident PD cases were identified through linkages with hospital admissions, death registers and self-reported data. Information on vital status, date of death and cause of death was obtained from the UK National Health Service (NHS) and the NHS Central Register. The multivariable Cox proportional hazards models were used to estimate the HRs and 95% CIs. During a median of 10.5 years of follow-up, 1047 participants had ≥3 prodromal PD features, 640 participants developed PD and 114 participants died from PD. Comparing extreme quartiles of UPF consumption, the HRs were 1.65 (95% CI: 1.35 to 2.02) for having ≥3 versus 0 prodromal PD features, 1.32 (95% CI: 1.02 to 1.71) for developing PD and 3.11 (95% CI: 1.56 to 6.17) for PD death (p value trend <0.05 for all). In this large prospective cohort study, higher UPF consumption was associated with higher risk of developing prodromal PD, incident PD and PD-specific mortality.

BoNT type A (BoNT-A) is a neurotoxic protein produced by the anaerobic bacterium Clostridium botulinum. In recent years, BoNT-A has demonstrated substantial efficacy in the management of various diseases, particularly neurological disorders, and has served as a versatile therapeutic agent in modern medicine. This review is aimed at comprehensively examining the application of BoNT-A in various non-dystonia disorders—including hyperhidrosis, salivation, chronic migraine, trigeminal neuralgia, postherpetic neuralgia, primary tremor, depression, and Parkinson’s disease—in the field of neurology.

Purpose: This study examines the efficacy of single photon emission computed tomography/computed tomography (SPECT/CT) guided BoNT-A injections for alleviating motor and non-motor symptoms in cervical dystonia (CD) patients. It also assesses the accuracy of SPECT/CT muscle imaging in identifying responsible muscles and analyzes the quantitative significance of the SUVmax index. Methods: A total of 102 patients diagnosed with primary cervical dystonia (CD) were recruited and assessed at baseline, as well as at 2, 4, 8, 12, and24 weeks post-botulinum toxin A (BoNT-A) injection. Among these patients, 79 underwent SPECT/CT imaging (SPECT/CT group), and 23 did not (control group). Both groups received BoNT-A injections guided by EMG, and their symptom improvements were compared. In the SPECT/CT group, the distribution of responsible muscles and its correlation with clinical phenotypes were analyzed. Furthermore, in a subset of 51 CD patients, overall and mean SUVmax of responsible muscles were quantified, and their correlation with the severity of motor symptoms was analyzed. Results: 1. In both the Tsui and TWSTRS scales, the SPECT/CT group (n=69) showed significantly higher overall improvement rates compared to the control group (n=23), with statistically significant differences. 2. In 79 CD patients, SPECT/CT imaging showed that common responsible muscles were the splenius capitis (SPCa), levator scapulae (Lev), splenius cervicis (SPCe), semispinalis capitis (SmCa), obliquus capitis inferior (OCI), and semispinalis cervicis (SSc). The deflection in CD patients was mainly influenced by the ipsilateral SPCa, SPCe, Lev, OCI, longissimus cervicis (LGc), and contralateral sternocleidomastoid muscle (SCM). 3. In 51 CD patients, significant positive correlations were found between overall SUVmax of responsible muscles and motor symptom scores, as well as between the mean SUVmax of responsible muscles and motor symptom scores. Conclusion: SPECT/CT muscle imaging significantly improves motor symptoms in CD patients when used for BoNT-A injections. It effectively identifies responsible muscles, and its SUVmax value serves as an objective indicator of motor symptom severity. SPECT/CT shows promise as a valuable tool for diagnosing and treating CD.

BackgroundThe effectiveness of Botulinum toxin type A (BTX-A) has been established in trigeminal neuralgia (TN). This study aimed to assess the therapeutic efficacy and safety of BTX-A injection within a group of TN patients who have chosen to continue BTX-A therapy.MethodsThis was a retrospective medical record-review study. Demographic and clinical features and severity and frequency of pain before and 4 weeks after the BTX-A administration were extracted from the patient files. BTX-A was injected into the painful area subcutaneously and/or submucosally. BTX-A injections were performed by the same physician using the same methods. Pain severity was assessed using the visual analog scale (VAS). The patient’s overall response to treatment was assessed using the Patient Global Impression of Change (PGIC). Patients were divided into two groups, single-treatment (TN-S) group and multiple-treatment (TN-M) group, according to the numbers of treatment.ResultsThirty patients were included in this study. We classified 16 (53.33%) as TN-S group and 14 (46.67%) as TN-M group. The median VAS score of all patients was 8 (6.75, 10) before the first treatment and 3 (2, 6.25) after the first treatment (P < 0.001). In the TN-M group, median of the difference of VAS before and after treatment of the first and the last treatment were 7 (5, 8) and 5 (2, 7.25), respectively, indicating a significantly better effect for the first treatment compared with the last treatment (P = 0.024). However, this difference in PGIC distributions between the two treatments was not significant (P = 0.070).ConclusionIn summary, BTX-A treatment was effective in TN. Elderly patients and patients with good response to the first treatment were more likely to choose to continue BTX-A multiple-treatments. BTX-A remains effective within a group of TN patients who have chosen to continue BTX-A therapy, but the efficacy decreases to a certain extent after multiple treatments.

Signaling mediated by brain-derived neurotrophic factor (BDNF), which is supported by the postsynaptic scaffolding protein PSD-95, has antidepressant effects. Conversely, clinical depression is associated with reduced BDNF signaling. We found that peptidomimetic compounds that bind to PSD-95 promoted signaling by the BDNF receptor TrkB in the hippocampus and reduced depression-like behaviors in mice. The compounds CN2097 and Syn3 both bind to the PDZ3 domain of PSD-95, and Syn3 also binds to an α-helical region of the protein. Syn3 reduced depression-like behaviors in two mouse models of stress-induced depression; CN2097 had similar but less potent effects. In hippocampal neurons, application of Syn3 enhanced the formation of TrkB–Gα i1/3 –PSD-95 complexes and potentiated downstream PI3K-Akt-mTOR signaling. In mice subjected to chronic mild stress (CMS), systemic administration of Syn3 reversed the CMS-induced, depression-associated changes in PI3K-Akt-mTOR signaling, dendrite complexity, spine density, and autophagy in the hippocampus and reduced depression-like behaviors. Knocking out Gα i1/3 in hippocampal neurons prevented the therapeutic effects of Syn3, indicating dependence of these effects on the TrkB pathway. The findings suggest that compounds that induce the formation of PSD-95–TrkB complexes have therapeutic potential to alleviate depression.

Objective: Botulinum toxin A has been shown to be effective in managing depression. This study aimed to evaluate the antidepressant and antianxiety effects of two different doses of botulinum toxin A in patients with mild to moderate depression. Methods: A total of 140 patients diagnosed with mild to moderate depression at the Department of Neurology of the Second Affiliated Hospital of Soochow University from September 2020 to September 2021 were enrolled for the study. The patients were allocated into two groups and treated with two different doses of botulinum toxin A (50 units or 100 units). Depression scores (HAMD, HAMA, SDS, and SAS) were evaluated at baseline and 1, 2, 4, 8, and 12 weeks after treatment. Results: There was a significant improvement in the depressive and anxiety symptoms following treatment with the botulinum toxin A after 12 weeks compared to the baseline. However, there were no significant differences between the two groups. Further, the factor scores of anxiety/somatization, blocking, sleep disorder, and cognitive disorder were significantly decreased after 12 weeks of treatment with 50 units of botulinum toxin A compared to the baseline (P < 0.05). Further, the factor scores of somatic and mental anxiety were significantly decreased at different time points after treatment with 50 units of botulinum toxin A compared to the baseline (P < 0.05). Conclusion: Local injections of 50 units and 100 units of botulinum toxin A shows equal efficacy. Therefore, 50 units of botulinum toxin A could be used clinically to manage mild to moderate depression.

Objective:Individual differences were observed in the clinical efficacy of Botulinum toxin A (BoNT-A) in the treatment of the primary Meige syndrome. Our study aimed to explore the potential associations between the clinical efficacy of BoNT-A in the treatment of the primary Meige syndrome and variants of SNAP25, SV2C and ST3GAL2, which are involving in the translocation of the BoNT-A in vivo. Methods:Patients with the primary Meige syndrome treated with BoNT-A were enrolled. Clinical efficacy was evaluated by the maximum improvement rate of motor symptoms and the duration of efficacy. Variants of SNAP25, SV2C and ST3GAL2 were obtained by Sanger sequencing. Another cohort diagnosed with primary cervical dystonia was also enrolled in the replication stage. Results:Among the 104 primary Meige syndrome patients, 80 patients (76.9%) had a good efficacy (the maximum improvement rate of motor symptoms ≥30%) and 24 (23. 1%) had a poor (the maximum improvement rate of motor symptoms <30%). As to the duration of efficacy, 52 patients (50.0%) had a long duration of efficacy (≥4 months), and 52 (50.0%) had a short (<4 months). In terms of primary Meige syndrome, SNAP25 rs6104571 was found associating with the maximum improvement rate of motor symptoms (Genotype: P = 0.02, OR = 0.26; Allele: P = 0.013, OR = 0.29), and SV2C rs31244 was found associating with the duration of efficacy (Genotype: P = 0.024, OR = 0.13; Allele: P = 0.012, OR = 0.13). Besides, we also conducted the association analyses between the variants and BoNT-A-related adverse reactions. Although, there was no statistical difference between the allele of SV2C rs31244 and BoNT-A-related adverse reactions, there was a trend (P = 0.077, OR = 2.56). In the replication stage, we included 39 patients with primary cervical dystonia to further expanding the samples' size. Among the 39 primary cervical dystonia patients, 25 patients (64.1%) had a good efficacy (the maximum improvement rate of motor symptoms ≥50%) and 14 (35.9%) had a poor (the maximum improvement rate of motor symptoms <50%). As to the duration of efficacy, 32 patients (82.1%) had a long duration of efficacy (≥6 months), and 7 (17.9%) had a short (<6 months). Integrating primary Meige syndrome and primary cervical dystonia, SV2C rs31244 was still found associating with the duration of efficacy (Genotype: P = 0.002, OR = 0. 23; Allele: P = 0.001, OR = 0. 25). Conclusion:In our study, SNAP25 rs6104571 was associated with the maximum improvement rate of motor symptoms in patients with primary Meige syndrome treated with BoNT-A, and patients carrying this variant had a lower improvement rate of motor symptoms. SV2C rs31244 was associated with duration of treatment in patients with primary Meige syndrome treated with BoNT-A and patients carrying this variant had a shorter duration of treatment. Patients with primary Meige syndrome carrying SV2C rs31244 G allele have an increase likelihood of BoNT-A-related adverse reactions. Involving 39 patients with primary cervical dystonia, the results further verify that SV2C rs31244 was associated with duration of treatment and patients carrying this variant had a shorter duration of treatment.

Objective: This study aimed to assess the efficacy of type A botulinum toxin treatment for androgenetic alopecia (AGA) using a combination of ultrasound and trichoscopy. Methods: Ninety patients with AGA who visited the Department of Dermatology at the Second Affiliated Hospital of Soochow University from September 2021 to December 2022 were prospectively selected. These patients met the diagnostic criteria outlined in the Chinese Guidelines for the Diagnosis and Treatment of Androgenetic Alopecia. The alopecia severity in the male patients ranged between grades 2 and 4 on the Norwood-Hamilton Scale. The patients were randomly assigned to receive injections of the same type of biological agent in a double-blind manner, with injection sites being the vertex or bilateral temporal-frontal hairline. In this study, the botulinum toxin group comprised 72 patients who received a biological agent with 100 units of type A botulinum toxin. The control group included 18 patients, and the biological agent administered to them contained 0 units of type A botulinum toxin. The patients were observed using 22-MHz ultrasound and trichoscopy before treatment, and 1 month and 3 months after treatment to compare the differences in various parameters at the injection sites. The ultrasound parameters included average follicle width, length, and count. The trichoscopy parameters were the number of hairs within a 1-cm(2) area on the counting scale. No artificial interventions were performed at the injection sites, and all examination conditions were consistent. Results: The patients in the botulinum toxin group had wider and longer average follicle width and length at the vertex 1 month and 3 months after treatment (p < 0.05), and wider and longer average follicle width and length in the left frontal area 3 months after treatment (p < 0.05) compared with those in the control group. The average follicle width and length gradually increased after treatment in the botulinum toxin group (p < 0.05), but no statistically significant differences were found in the control group (p > 0.05). The patients in the botulinum toxin group exhibited greater average follicle lengths after treatment at the vertex compared with the left frontal area (p < 0.05). No statistically significant differences were found in follicle count (p > 0.05) or hair count (p > 0.05) between the botulinum toxin and control groups after injection treatment. Conclusions: The follicle width and length are effective parameters for evaluating the efficacy of type A botulinum toxin treatment for AGA. Ultrasound revealed that the changes in follicles at the vertex occurred earlier than those in the left frontal area following treatment. Additionally, the changes in follicles were detected earlier than the changes in hair count using ultrasound. Ultrasound combined with trichoscopy provided more parameters for evaluating the efficacy of type A botulinum toxin treatment for AGA, resulting in a more comprehensive evaluation.

Background How physical activity (PA) and different sleep traits and overall sleep pattern interact in the development of Parkinson’s disease (PD) remain unknown. Objective To prospectively investigate the joint associations of PA and sleep pattern with risk of PD. Methods Included were 339,666 PD-free participants from the UK Biobank. Baseline PA levels were grouped into low (< 600 MET-mins/week), medium (600 to < 3000 MET-mins/week) and high (≥ 3000 MET-mins/week) according to the instructions of the UK Biobank. Healthy sleep traits (chronotype, sleep duration, insomnia, snoring, and daytime sleepiness) were scored from 0 to 5 and were categorized into “ideal sleep pattern” (≥ 3 sleep scores) and “poor sleep pattern” (0–2 sleep scores). Hazard ratios (HRs) and 95% confidence intervals (CIs) of PD were estimated by Cox proportional hazards models. Results During a median of 11.8 years of follow-up, 1,966 PD events were identified. The PD risk was lower in participants with high PA (HR = 0.73; 95% CI: 0.64, 0.84), compared to those with low PA; and participants with ideal sleep pattern also had a lower risk of PD (HR = 0.78; 95% CI: 0.69, 0.87), compared to those with poor sleep pattern. When jointly investigating the combined effect, participants with both high PA and ideal sleep pattern had the lowest risk of incident PD (HR = 0.55; 95% CI: 0.44, 0.69), compared to those with low PA and poor sleep pattern; notably, participants with high PA but poor sleep pattern also gained benefit on PD risk reduction (HR = 0.74; 95% CI: 0.55, 0.99). Conclusions Both high PA and ideal sleep pattern were independently associated with lower risk of developing PD, and those with both high PA level and ideal sleep pattern had the lowest risk. Our results suggest that improving PA levels and sleep quality may be promising intervention targets for the prevention of PD.

BackgroundPost-stroke depression (PSD) is a frequent complication following a stroke, characterized by prolonged feelings of sadness and loss of interest, which can significantly impede stroke rehabilitation, increase disability, and raise mortality rates. Traditional antidepressants often have significant side effects and poor patient adherence, necessitating the exploration of more suitable treatments for PSD. Previous researchers and our research team have discovered that Botulinum Toxin A (BoNT-A) exhibits antidepressant effects. Therefore, our objective was to assess the efficacy and side effects of BoNT-A treatment in patients with PSD.MethodsA total of 71 stroke patients meeting the inclusion criteria were allocated to the two group. 2 cases were excluded due to severe neurological dysfunction that prevented cooperation and 4 cases were lost follow-up. Ultimately, number of participants in the BoNT-A group (n = 32) and Sertraline group (n = 33). Treatment efficacy was evaluated 1, 2, 4, 8 and 12 weeks post-treatment.ResultsThere were no significant differences in baseline characteristics between the two groups (p > 0.05). Both groups exhibited comparable treatment efficacy, with fewer side effects observed in the BoNT-A group compared to the Sertraline group. BoNT-A therapy demonstrated significant effects as early as the first week (p < 0.05), and by the 12th week, there was a notable decrease in neuropsychological scores, significantly lower than the baseline level. The analysis revealed significant differences in measurements of the Hamilton Depression Scale (HAMD) (F(770) = 12.547, p = 0.000), Hamilton Anxiety Scale (HAMA) (F(951) = 10.422, p = 0.000), Self-Rating Depression Scale (SDS) (F(1385) = 10.607, p = 0.000), and Self-Rating Anxiety Scale (SAS) (F(1482) = 11.491, p = 0.000).ConclusionBoNT-A treatment effectively reduces depression symptoms in patients with PSD on a continuous basis.

BackgroundThe status of vitamin D has been proposed to have an impact on cognition. Gray matter volume (GMV) is a potential marker of cognitive function. We investigated whether lower serum 25-hydroxyvitamin D level was associated with reduced cerebral GMV in Parkinson’s disease with non-dementia (PDND) patients.MethodsBaseline neuropsychiatric performance and serum 25-hydroxyvitamin D levels were examined in 24 PDND patients and 24 healthy controls (HCs). A set of cognitive scales were used to evaluate the cognition. Voxel-based morphometry (VBM) was performed to calculate each PDND patient’s GMV, based on structural magnetic resonance imaging data. Associations between serum 25-hydroxyvitamin D levels, cognition, and GMV were evaluated.ResultsThe serum 25-hydroxyvitamin D levels of the PDND group were significantly lower than those of the HC group. The simple linear regression analyses between serum 25-hydroxyvitamin D levels and the scores of subtests that analyzed cognitive function showed that serum 25-hydroxyvitamin D levels were negatively correlated with Trail Making Test-A scores and positively correlated with Symbol Digit Modalities Test and Auditory Verbal Learning Test scores. Multiple regression analyses revealed a positive correlation between the right fusiform gyrus GMV and serum 25-hydroxyvitamin D levels.ConclusionWe hypothesized that the lower serum 25-hydroxyvitamin D level in patients with PDND might affect auditory word learning and spatial cognition ability by reducing the gray matter volume of the right fusiform gyrus, thereby leading to deterioration of semantic understanding and memory function.

AbstractBackgroundHigh‐frequency repeated transcranial magnetic stimulation (rTMS) stimulating the primary motor cortex (M1) is an alternative, adjunctive therapy for improving the motor symptoms of Parkinson's disease (PD). However, whether the high frequency of rTMS positively correlates to the improvement of motor symptoms of PD is still undecided. By controlling for other parameters, a disease animal model may be useful to compare the neuroprotective effects of different high frequencies of rTMS.ObjectiveThe current exploratory study was designed to compare the protective effects of four common high frequencies of rTMS (5, 10, 15, and 20 Hz) and iTBS (a special form of high‐frequency rTMS) and explore the optimal high‐frequency rTMS on an animal PD model.MethodsFollowing high frequencies of rTMS application (twice a week for 5 weeks) in a MPTP/probenecid‐induced chronic PD model, the effects of the five protocols on motor behavior as well as dopaminergic neuron degeneration levels were identified. The underlying molecular mechanisms were further explored.ResultsWe found that all the high frequencies of rTMS had protective effects on the motor functions of PD models to varying degrees. Among them, the 10, 15, and 20 Hz rTMS interventions induced comparable preservation of motor function through the protection of nigrostriatal dopamine neurons. The enhancement of brain‐derived neurotrophic factor (BDNF), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT‐2) and the suppression of TNF‐α and IL‐1β in the nigrostriatum were involved in the process. The efficacy of iTBS was inferior to that of the above three protocols. The effect of 5 Hz rTMS protocol was weakest.ConclusionsCombined with the results of the present study and the possible side effects induced by rTMS, we concluded that 10 Hz might be the optimal stimulation frequency for preserving the motor functions of PD models using rTMS treatment.

Neurotoxins generally inhibit or promote the release of neurotransmitters or bind to receptors that are located in the pre- or post-synaptic membranes, thereby affecting physiological functions of synapses and affecting biological processes. With more and more research on the toxins of various origins, many neurotoxins are now widely used in clinical treatment and have demonstrated good therapeutic outcomes. This review summarizes the structural properties and potential pharmacological effects of neurotoxins acting on different components of the synapse, as well as their important clinical applications, thus could be a useful reference for researchers and clinicians in the study of neurotoxins.