Freezing of gait (FOG) is a complex and highly disabling motor symptom that frequently affects patients with Parkinson’s disease (PD), especially in the middle and late stages. Although traditionally associated with motor deficits, accumulating evidence suggests that FOG is also strongly influenced by non-motor domains, including cognitive dysfunction and emotional disturbances. The prefrontal cortex (PFC), a key hub for executive functions, attention, and emotional regulation, has been increasingly implicated in the pathophysiology of FOG. Structural and functional abnormalities in the PFC, particularly in the dorsolateral prefrontal cortex (DLPFC) and medial prefrontal cortex (MPFC), have been reported in PD patients with FOG. This narrative review aims to summarize current evidence on the role of the prefrontal cortex in the development and modulation of freezing episodes, focusing on neuroimaging findings. Clarifying the contribution of frontal lobe dysfunction to FOG may inform therapeutic strategies targeting frontostriatal circuits to improve mobility and quality of life in PD patients. This is a narrative review and does not employ formal systematic review methodology.

Background:Sleep disturbances are common non-motor symptoms in Parkinson's disease (PD), significantly diminishing patients' quality of life. Management typically involves sleep hygiene education, psychotherapy, pharmacological and non-pharmacological interventions. This study aims to explore the safety and effectiveness of repeated lower extremity hot water bathing (REHAB) as a potential treatment for sleep disorders in this patient population. Methods:This is a randomized, controlled, open-label with trial outcome assessment. A total of 40 elderly patients with advanced PD will be enrolled and randomly assigned (1:1) to either a REHAB group or a control group. The control group will receive guideline-based usual care. While the REHAB group will receive the same usual care plus 30-min REHAB sessions, conducted daily for 5-7 days per week over 4 weeks, followed by a 2-week observation period. The primary objective of this study is to evaluate the safety of REHAB in elderly patients with advanced PD. These safety concerns include orthostatic hypotension associated with autonomic dysfunction, scalds or intolerance to hot water bathing due to sensory disorders (both common in PD patients), and signs of tissue damage. Secondary objectives include evaluating the impact of REHAB on sleep quality using the Parkinson's Disease Sleep Scale (PDSS) and polysomnography (PSG) at weeks 0, 4, and 6. Discussion:This novel randomized controlled trial will assess the safety and potential therapeutic benefits of REHAB for sleep disorders in elderly patients with advanced PD. The findings will inform design considerations for future phase III studies and may introduce a new rehabilitation strategy for managing sleep disturbances in this population. Trial registration:http://www.chictr.org.cn/, identifier: ChiCTR2400092087.

Fatigue is a common and debilitating non-motor symptom in Parkinson’s disease (PD), significantly impairing patient quality of life and often observed in clinical management. Its pathophysiology involves complex interactions among dopaminergic, non-dopaminergic, and neuroinflammatory pathways. Although fatigue is highly prevalent, evidence-based treatment strategies remain limited. This review is based on a targeted literature search focusing on recent advances in research on PD-related fatigue. Using a combination of keywords such as "Parkinson's disease", "fatigue", "non-invasive brain neurostimulation techniques", "repetitive transcranial magnetic stimulation ", and "transcranial direct current stimulation ", relevant articles published between 2000 and 2025 were selected. While pharmacological approaches, such as rasagiline, have shown some promise, their therapeutic effects remain inconsistent and limited. Recently, non-invasive brain stimulation (NIBS) techniques, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), have emerged as promising non-pharmacological interventions. Preliminary studies indicate that rTMS may help quantify central fatigue through motor evoked potential (MEP) modulation, while tDCS applied to cortical targets like M1 and DLPFC appears to reduce fatigue severity and improve cognitive processing. Despite theirpotential, current evidence is restrained by small sample sizes, heterogeneity in protocols, and a lack of standardized outcome measures. This review summarizes the clinical features, diagnostic criteria, and current therapeutic strategies for PD-related fatigue,with a focus on the emerging role of NIBS. Future research should prioritize well-designed, large-scale randomized controlled trials tooptimize stimulation parameters and validate the long-term efficacy of NIBS in fatigue management for PD patients.

Objective:Alzheimer's disease (AD) is characterized by complex pathological mechanisms involving neuroinflammation, oxidative stress, and vascular dysfunction. Remote Ischemic Conditioning (RIC) has shown potential in addressing these pathways by improving cerebral blood flow, reducing oxidative stress, and modulating inflammatory responses. This protocol focuses on evaluating the safety, feasibility, and preliminary efficacy of RIC as a multi-target intervention for delaying cognitive decline in patients with mild Alzheimer's dementia, aiming to improve cognitive outcomes and overall quality of life. Methods and expected results:This study is a randomized, controlled, single-center, prospective clinical trial designed to evaluate the safety, feasibility, and preliminary efficacy of RIC in patients with mild Alzheimer's dementia. Eligible participants will be recruited and randomly assigned to either the RIC group or a control group receiving sham RIC, with 20 patients in each group. Participants will receive either RIC or sham RIC once daily over a 3-month period. Outcome measures will assess cognitive function, psychological well-being, and inflammatory and neurodegenerative biomarkers. Psychiatric adverse events will be monitored throughout the treatment using the Hamilton Anxiety Rating Scale (HAMA) and the Hamilton Depression Rating Scale (HAMD-17). Cognitive function and daily living abilities will be evaluated at baseline, 3 months, 6 months, and 12 months post-treatment using the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating (CDR), and the Activities of Daily Living (ADL) scales. In addition, blood samples will be collected at each time point to measure plasma biomarkers of β-amyloid species and serum inflammatory cytokines to assess potential changes in cognitive decline, disease progression, and inflammation. The primary endpoint is safety, with the expectation that RIC will not increase psychiatric adverse events as reflected in HAMA and HAMD-17 scores. Primary efficacy endpoints include improvements in MMSE, MoCA, CDR, and ADL scores, indicating potential cognitive benefits and enhanced daily functioning. Secondary endpoints will analyze biomarkers to evaluate disease progression and inflammation levels before and after treatment. Conclusion:This trial aims to determine the safety, feasibility, and potential effectiveness of RIC as a multi-target intervention for mild Alzheimer's dementia by integrating cognitive and neuropsychological assessments with biological markers, providing a foundation for future studies.

ObjectiveSleep disturbances are common non-motor symptoms of Parkinson's disease. The symptoms affect the quality of patients' life by impeding normal sleep cycles and causing excessive daytime sleepiness. Remote Ischemic Conditioning (RIC) is a therapy often used for ischemic stroke patients to minimize infarct size and maximize post-stroke neurological function. Animal experiments have shown that RIC plays a protective role for retinal ganglion cells and other critical areas of the brain of Parkinson's disease. However, whether RIC improves excessive daytime sleepiness (EDS) for patients with Parkinson's disease remains to be determined.MethodsThis is a single-center, double-blind, and randomized controlled trial, which includes patients with Parkinson's disease with EDS. All recruited patients will be randomly assigned either to the RIC or the control group (i.e., sham-RIC) with 20 patients in each group. Both groups receive RIC or sham-RIC treatment once a day for 28 days within 24 h of enrollment. Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Parkinson Disease Sleep Scale-2 (PDSS-2), Parkinson's Disease Questionnaire39 (PDQ39) score scales, and adverse events, such as inability to tolerate the treatment leading to suspension of the study or objective signs of tissue or neurovascular injury caused by RIC and/or sham-RIC are evaluated at 7, 14, 28, and 90 days after enrollment.ResultsThe primary goal of this study is to assess the feasibility of the treatments in patients with Parkinson's disease by measuring serious RIC-related adverse events and any reduced incidence of adverse events during the trial and to study potential efficacy, improvement of patients' excessive daytime sleepiness, quality of life-based on ESS, PSQI, PDSS-2, and PDQ39 scores. The secondary goal is to confirm the safety of the treatments.ConclusionThis study is a prospective randomized controlled trial to determine the safety, feasibility, and potential efficacy of RIC for patients with Parkinson's disease associated with EDS.

Objective:The present study sought to differentiate multiple sclerosis and neuromyelitis optica spectrum disorder patients at their first attack by describing and distinguishing their clinical features, radiographic characteristics, and immunologic characteristics of serum and cerebrospinal fluid.Methods:We retrospectively studied 58 patients with multiple sclerosis (MS) and 52 patients with neuromyelitis optica spectrum disorder (NMOSD) by referencing brainstem lesions as the prodromal events. Their demographics and presentation at the time of the first attack was evaluated including their gender, age, clinical features of the first attack, the expanded disability status scale (EDSS), brainstem lesion(s) by head MRI, and immunological indices of serum and cerebrospinal fluid.Results:The NMOSD group had more female patients (4.8 vs. 1.9, p < 0.05), and was older than the MS group (37.81 ± 16.60 vs. 27.57 ± 11.17, p <0.001). NMOSD patients also had a significantly higher association with autoimmune diseases or positive autoimmune antibodies (p < 0.01). There was no significant difference in the EDSS scores between the two groups (p = 0.420). Central hiccups, vomiting, and pyramidal tract signs were more common in the NMOSD group than the MS group (p < 0.001, p < 0.001, p < 0.01), while eye movement abnormalities were more common with MS (p < 0.01). There were no significant differences in other clinical manifestations such as vertigo, diplopia, limb weakness, numbness, and eating difficulty. MS patients were more likely to have midbrain and pons imaging lesions (p < 0.001, p < 0.001), while NMOSD patients had more lesions in the medulla oblongata (p < 0.001). The lesions in the MS group were mostly located in the periphery, while those in the NMOSD group were centrally located (p < 0.001, p < 0.001). Patchy lesions were more common in MS patients (p < 0.001), while large lesions were more common in the NMOSD group (p < 0.001). Finally, serum AQP4 Ab was found only in the NMOSD group (p < 0.001).Conclusion:Patients with MS and NMOSD have differentiating clinical manifestations at the time of their first brainstem lesions which include central hiccups, vomiting, pyramidal tract signs, and abnormal eye movements. Additionally, distinct imaging manifestations such as lesion location(s) and morphology may also aid in the development of pathognomonic criteria leading to timely initial diagnosis of MS and NMOSD.

Objective Toinvestigatethetypicalclinicalcharacteristics,imagingfindingsand drug therapyofdiabetichemiballism-hemichorea (DHB-HC). Methods Literaturerelatedto DHB-HC case reportsincludedin MedlinedatabasefromJanuary1,2008toJune30,2018 weresearchedaccordingtostrict standards,andtheclinicalmanifestations,imagingcharacteristicsandprognosisoftheDHB-Hcpatientswere reviewed.Results 23papersinvolving53patientswerefinallyincluded.35cases (66.0%)wereAsianpatients. Therewere13males(24.5%)and40females(75.5%),agedfrom14to91yearsold,withamedianageof74 (interquartilerange:16yearsold).5patients (9.4%)showedbilateraldancingsymptoms,and48patients (90.6%)showedhemidancingsymptoms. MRexaminationwasperformedin42patientsandhyperintensityin T1-weightedimaging wasfoundin33patients (78.6%). 24ofthe53patients (45.3%)hadspontaneous remissionbyhypoglycemictherapyonly,29patients (54.7%)hadremissionbyadditionalallopathicdrug,3 patients(5.7%)relapsedwithin1year.Conclusions DHB-HCiscommonlyseeninelderlyAsianwomen.Its characteristicsaremostlyone-sidedsymptoms;hyperglycemia,hyperglycosylatedhemoglobin,negativeketone body,andhyperintensityinT1imageatbasalgangliapresentattheonset. Activecontrolofbloodglucoseand symptomatictreatmentarehelpfultoshortenthecourseofdiseaseandimprovetheprognosis.

Objective To investigate the clinical features of bilateral medial medullary infarction (BMMI)in elderly patients.Methods Clinical and imaging data of 8 elderly BMMI patients with different morphology on diffusion-weighted magnetic resonance imaging (DWI-MR) were retrospectively analyzed.All patients were diagnosed by MRI,while 4 patients received CTA and vascular ultrasound testing,and the other 4 patients received vascular ultrasound testing.Results All 8 cases(100.0％) had acute-onset BMMI.Patients showed varying degrees of acroparalysis(7/8,87.5 ％),dizziness (5/8,62.5 ％),dysarthria(6/8,80.0 ％),dysphagia(3/8,37.5 ％),deep or superficial sensory dysfunction(5/8,62.5 ％),consciousness disorders (2/8,25.0 ％),dyspnea (2/8,25.0 ％),and tinnitus(1/8,12.5 ％).Lesions in most patients were located in the upper part of medulla oblongata(7/8,87.5 ％).In the transverse direction of DWI,the lesions as the inverted V shape were seen in 3 cases (37.5％),the V shape(12.5％)in 1 case,the Y shape(37.5％)in 3 cases,and the heart shape(12.5％) in 1 case.All 8 patients were complicated with posterior cerebral artery stenosis or occlusion,of whom patients with heart-or Y-shaped lesions showed progressive exacerbation.After treatment,4 cases (50.0 ％) recovered,3 cases (37.5 ％) improved,and 1 case (12.5 ％) unrecovered before discharge from the hospital.Conclusions Most elderly BMMI patients have concurrent posterior circulation artery stenosis,and patients with heart-or Y-shaped lesions on MR-DWI show rapid progression and have a poor prognosis.Cranial examination with MR-DWI is helpful for early clinical diagnosis of BMMI,prediction of disease progression and effective prevention of complications.

Propose: To investigate whether miR-22-3p is able to regulate AD development and its molecular mechanism.METHODS:Morris water maze test was performed to test the spatial memory. Quantitative polymerase chain reaction (qPCR) was used to assess the expression level of miR-22-3p. The enzymelinked immunosorbent assay (ELISA) was used to assess the levels of Aβ40 and Aβ42. Immunoblotting analysis was performed to detect the protein expression levels of amyloid precursor protein (APP), mitogen-activated protein kinase 14 (MAPK14) and beta-site Amyloid precursor protein Cleaving Enzyme 1 (BACE1). Luciferase assay was used to identify the interaction between miR- 22-3p and MAPK14. The tetrazolium dye (MTT) colorimetric assay was used to test the influence of miR-22-3p overexpression on cell viability. Flow cytometry analysis was performed to evaluate the effect of miR-22-3p overexpression on cell apoptosis.RESULTS:Morris water maze test showed that mice model of AD had impaired spatial memory, which was able to be ameliorated by miR-22-3p overexpression. Immunoblotting analysis revealed that the protein expression levels of APP, MAPK14 and BACE1 were enhanced in AD model, which could be prevented by miR-22-3p overexpression. ELISA showed that Aβ40 and Aβ42 levels were dramatically increased in AD model, which were inhibited by miR-22-3p overexpression. Luciferase assay and immunoblotting analysis indicated that miR-22-3p targeted and regulated MAPK14 expression.CONCLUSION:MiR-22-3p overexpression reduced Aβ deposit and alleviated AD symptoms by targeting and regulating MAPK14 expression, which ameliorated AD symptoms.

Objective To investigate the relationship between serum homocysteine (Hcy) and seizure control as well as cognitive impairment in patients with epilepsy (MCI).Methods A total of 128 cases of epilepsy patients were enrolled and assessed for cognitive function with Mini-Mental State Evaluation Scale (MMSE). According to the existence of MCI, all the subjects were assigned into MCI group (n=46), and non-MCI group (n=82). The levels of folic acid, Hcy, vitamin B12 in serum of patients were determined by chemiluminescence immunoassay. The correlation between serum Hcy and the score of MMSE were analyzed by Pearson correlation analysis. High homocysteine (HHcy) epilepsy patients were treated with folic acid and vitamin B. The serum Hcy level and the seizure frequency were analyzed before treatment, 3 months and 6 months after treatment.Results The serum Hcy level of HHcy patients at 3 months and 6 months after treatment decreased significantly, so as the seizure frequency (P<0.01). Compared with non-MCI group, serum folic level and vitamin B12 decreased significantly(P<0.05), while the Hcy level increased (P<0.01). When serum Hcy was less than 15.00 μmol/L, there was no significant correlation with MMSE (r=-0.18,P>0.05). When serum Hcy level was between 15.0~20.0 μmol/L and over 20.0 μmol/L,there was a negative correlation between MMSE and serum Hcy level (r=-0.39,-0.56;P<0.05).Conclusions Giving vitamin B12 intervention to HHcy epilepsy patients can reduce serum Hcy levels and the frequency of seizures. Whether the level of Hcy in epileptic patients can be used as a biological predictor of MCI in epileptic patients still needs to be classified accurately.

目的:探讨同型半胱氨酸(Hcy)、糖化血红蛋白(HbAlc)、神经胶质纤维酸性蛋白(GFAP)在急性缺血性卒中患者中的表达及意义.方法:选择2015年10月至2016年10月我院接诊的急性缺血性卒中患者80例,作为观察组,并选择同期我院接诊的健康体检人群80例,作为对照组.使用酶联免疫吸附法(ELISA)检测所有受试者Hcy、HbAlc、GFAP的表达,并比较不同梗死程度、不同病情严重程度、不同预后急性缺血性卒中患者Hcy、HbAlc、GFAP的表达,分析Hcy、HbAlc、GFAP和急性缺血性卒中的关系.结果:观察组Hcy、HbAlc、GFAP均明显高于对照组(P<0.05);随着患者梗死面积的增加、病情严重程度的增加,Hcy、HbAlc、GFAP的表达也随之增加,比较均具有显著差异(P<0.05);预后不良组患者Hcy、HbAlc、GFAP明显高于预后良好组(P<0.05);经Pearson相关分析显示,Hcy、HbAlc、GFAP和美国国立卫生研究院卒中量表(NIHSS)评分、脑梗死面积之间均呈正相关(P<0.05);且在Logistic回归中显示,Hcy、HbAlc、GFAP均是影响急性缺血性卒中患者预后的危险因素(P<0.05).结论:Hcy、HbAlc、GFAP均是影响急性缺血性卒中神经功能缺损程度和预后的独立危险因素,可作为诊断、治疗、评估病情的重要指标,临床应用价值高.

目的 探讨神经肌肉电刺激治疗仪治疗吞咽障碍的疗效.方法 伴有吞咽障碍的急性脑卒中患者90例,分为真性球麻痹组30例,假性球麻痹组60例,应用神经肌肉电刺激治疗仪治疗吞咽困难,每组再各自随机平均分为每日治疗1次亚组和每日治疗2次亚组.在治疗前、治疗后15 d、3个月进行洼田饮水试验分级评估及疗效评价.结果 真性球麻痹组和假性球麻痹组治疗前与治疗后15 d、3个月洼田饮水试验分级差异均有统计学意义(均P<0.01);治疗后15 d两组差异有统计学意义(P=0.030),治疗后3个月两组差异无统计学意义(P=0.285).两组治疗后15 d及3个月疗效比较差异有统计学意义(P=0.011,0.047);真球治疗1次组和2次组治疗后15 d疗效差异有统计学意义(P=0.014),而治疗后3个月差异无统计学意义(P=0.172);假球治疗2次组治疗后15 d及3个月疗效显著优于假球治疗1次组(P<0.01).结论 神经肌肉电刺激治疗对脑卒中患者吞咽困难疗效明显,而假性球麻痹患者比真性球麻痹患者效果更好,增加治疗次数至每日2次效果优于每日治疗1次.

Although changes in brain gray matter after stroke have been identified in some neuroimaging studies, lesion heterogeneity and individual variability make the detection of potential neuronal reorganization difficult. This study attempted to investigate the potential structural cortical reorganization after sub-cortical stroke using a longitudinal voxel-based gray matter volume (GMV) analysis. Eleven right-handed patients with first-onset, subcortical, ischemic infarctions involving the basal ganglia regions underwent structural magnetic resonance imaging in addition to National Institutes of Health Stroke Scale (NIHSS) and Motricity Index (MI) assessments in the acute (<5 days) and chronic stages (1 year later). The GMVs were calculated and compared between the two stages using nonparametric permutation paired t-tests. Moreover, the Spearman correlations between the GMV changes and clinical recoveries were analyzed. Compared with the acute stage, significant decreases in GMV were observed in the ipsilesional (IL) precentral gyrus (PreCG), paracentral gyrus (ParaCG), and contralesional (CL) cerebellar lobule VII in the chronic stage. Additionally, significant increases in GMV were found in the CL orbitofrontal cortex (OFC) and middle (MFG) and inferior frontal gyri (IFG). Furthermore, severe GMV atrophy in the IL PreCG predicted poorer clinical recovery, and greater GMV increases in the CL OFG and MFG predicted better clinical recovery. Our findings suggest that structural reorganization of the CL “cognitive” cortices might contribute to motor recovery after sub-cortical stroke.

Objective To study the effect of neuromuscular electrical stimulation to anxiety-depression in patients with cerebral infarction.Methods 126 patients with post-stroke dysphagia, swallowing function divided into III class(n=52), IV class(n=45), V class(n=29)according to via the water swallow tests,Patients were evaluated with scores of Hamilton anxiety rating scale( HAMA), Hamilton depression( HAMD) at different levels,then 126 patients with post – stroke dysphagia were randomized into the treatment group(n=66) and the control group(n =60).Patients in two groups received conventional drug therapy and swallowing function training, while the patients in the treatment group received NES in addition.Patients were evaluated with scores of Hamilton anxiety rating scale (HAMA) and Hamilton depression ( HAMD) before and after treatment.Results The scores of depression and anxiety were positively correlated swallowing dysfunction severity.After treatment for two courses , somatic anxiety, psychic anxiety and the total of the treatment group in HAMA were improved (P<0.05),anxiety, body weight, cognitive disturbance, inhibition, hopeleness the total of the treatment group in HAMD were improved (P<0.05) than those before treatment and those in control group.Conclusion Depression and anxiety of patients with post-stroke dysphagia were positively correlated swallowing dysfunction severity.Neuromuscular electrical stimulation applied in patients with cerebral infarction could improve anxiety-depression.

Objective To investigate the reorganization in remote cerebral areas after sub-cortical infarction by using a longitudinal voxel-based gray matter volume (GMV) analysis.Methods Eleven patients with ischemic stroke that involved sub-cortical regions underwent structural magnetic resonance imaging (MRI) within 5 days and three months after the onset of the infarction.The patients were evaluated using National Institutes of Health Stroke Scale (NIHSS) and Motricity Index (MI).Using VBM method the GMV of the acute stage and chronic stage was calculated and the results were compared between the two stages.The correlation between GMV and rehabilitation indexes (NIHSS and MI) was analyzed.Results Compared with the acute stage,significant decrease in GMV was found in the ipsi-lateral precentral gyrus (PreCG),midcingulate cortex and contralesional cerebellar lobule Ⅵ (CBVI),cerebellar lobule Crus 1 in the chronic stage,while significant increase in GMV was seen in the contra-lateral precentral gyrus,orbitofrontal cortex (OFC),ventral prefrontal cortex,and ipsi-lateral cerebellar lobule Crus 1.Furthermore,the GMV at bilateral PreCG and contralesional CBVI,OFC was well correlated with NIHSS and MI scores.Conclusion There is widely distributed reorganization in the remote cerebral cortex after sub-cortical infarction,which might be linked to the prognosis.Further studies are needed to clarify the mechanism of the recovery of neural function following sub-cortical infarction.

目的探讨预测脑梗死早期病情进展的危险因素。方法将70例进展型脑梗死与同期住院随机抽取的106例非进展型脑梗死的临床资料进行对照分析。结果进展组患者平均年龄为62.44±9.13a,非进展组患者的平均年龄为58.57±10.82a,(P<0.05);进展组有近期感染史21例,非进展组有8例,二者有显著性的差异(X2=15.44,P<0.01);进展组有糖尿病史25例,非进展组有15例,二者有显著性差异(X2=11.16,P<0.01);进展组有高脂血症史46例,非进展组有43例,二者有显著性差异(X2=10.67,P<0.01)。进展组与非进展组在高血压病史、吸烟、性别构成比方面无显著性差异。结论高龄、近期感染、糖尿病、高脂血症是预测脑梗死早期病情进展的危险因素。

1 病历简介 患者,男性,70岁,主因"被发现言语不能,右侧肢体活动不利6小时,发作性抽搐2小时"入院.既往高血压病史20余年,脑梗塞病史2年,未遗留后遗症.入院后查体:BP180/100mmHg,神志清楚,不全混合性失语,颈抗(-),双眼向右注视不到边,眼震(-),双瞳孔￠3.0mm,光反应(++).