Therapeutic Advances in Neurological Disorders最新文献

We describe here the first case of cerebral air embolism (CAE) due to a dysfunctional long-term central venous catheter for hemodialysis in a 39-year-old woman with a history of lung transplantation. Air emboli are rare but potentially fatal complications of hemodialysis, in particular, when they involve the brain. Early management with hyperbaric oxygen therapy (HBOT) is critical to prevent deterioration of the patient's condition. In this case, our patient presented her first symptoms, likely a seizure due to multiple cerebral air emboli, during her hemodialysis session. She was then monitored in the Nephrology Intensive Care Unit in accordance to the medical reference center (with HBOT). Twelve hours later, she experienced secondary deterioration, presenting with acute aphasia, left hemineglect syndrome, and hemiplegia. She was rapidly transferred to the medical reference center for HBOT. The patient fully recovered after receiving three sessions of HBOT. She also presented a seizure during each HBOT session, attributed to hyperoxia. She never experienced another seizure after the episode of CAE. This case highlights the importance of considering patients who have a lung transplant to be at increased risk for air emboli during hemodialysis and the need to rapidly recognize symptoms and start treatment, including HBOT, to optimize recovery.

Background: Patients with multiple sclerosis (PwMS) have an increased risk of infections.

Objectives: To characterize incidence, clinical characteristics, outcomes and risk factors of infections, and serious infections (SIs) in ocrelizumab (OCR)-treated PwMS.

Design: Post-hoc analysis of pooled data from 6155 patients in 13 clinical trials.

Methods: Descriptive analyses of clinical characteristics and outcomes were reported over ⩽14 years. A Poisson Generalized Estimating Equation model was constructed to examine risk factors in a subgroup of patients with longer exposure to OCR (n = 2092).

Results: Over a median (max) treatment period of 3.7 (13.9) years, 420/6155 patients (6.8%) experienced 583 SIs, excluding coronavirus disease 2019. Incidence rates in relapsing multiple sclerosis (RMS; 1.50 per 100 patient years [95% confidence interval (CI): 1.34-1.68]) and progressive multiple sclerosis (PMS; 3.70 [95% CI: 3.27-4.17]) remained stable over this period. Lower respiratory tract, urinary tract, abdominal and gastrointestinal, and skin infections were the most commonly reported SIs. Most SIs (~90%) resolved, and treatment with OCR was continued in >80% of cases. The presence of 1 or ⩾2 comorbidities (rate ratio = 1.66, 2.73, respectively), recent relapse activity (2.06), and Expanded Disability Status Scale (EDSS) score ⩾6.0 (2.02) were significant risk factors for SIs in patients with RMS treated over a median (max) period of 8.3 (11.2) years. In patients with primary PMS treated over a median (max) period of 7.1 (11.8) years, an EDSS score ⩾6.0 was associated with the greatest risk of SIs, a 4-fold increase (rate ratio, 4.31), followed by abnormal immunoglobulin (Ig)M levels (1.89), the presence of ⩾2 comorbidities (1.80), and having overweight/obesity (1.46). Time on OCR and abnormal IgG levels were not significantly associated with an increased SI risk.

Conclusion: Continuous long-term treatment with OCR is associated with a manageable infection risk profile. Optimal disease control and addressing modifiable risk factors may reduce the risk of infections.

Background: Although managing symptoms is paramount for both essential tremor (ET) patients and their healthcare providers, studies of treatment satisfaction are surprisingly lacking.

Objectives: We evaluated the satisfaction of patients who used a range of treatments and assessed the relation of a wide array of factors to satisfaction.

Methods: One hundred four ET participants (age = 74.5 ± 10.2 years) completed a battery of self-report items. These included demographic information, measures of tremor and clinical history, psychological state, current ET treatment, and a series of questions about satisfaction with treatment.

Results: Analyses of responses to the four current treatment satisfaction questions revealed that the proportion of participants who were satisfied ranged from 35.0% to 57.3% (i.e., approximately 1/3 to 1/2); conversely, the proportion who were dissatisfied ranged from 9.2% to 37.0%. The remainder were neutral. Higher satisfaction levels were observed in participants who were included in treatment selection and who had undergone deep brain stimulation surgery, p's < 0.05. Lower levels of satisfaction were found in participants with a negative psychological state, higher self-rated tremor severity, head/voice/jaw tremors, and more severe physical side effects; and who used botulinum toxin therapy, p's < 0.05.

Conclusion: Between 1/3 and 1/2 of patients were satisfied with their treatment, whereas up to 1/3 were dissatisfied. In this initial exploration of correlates of treatment satisfaction in ET patients, we identified a number of associations between satisfaction and clinical, psychological and treatment variables. Additional research is warranted to further explore the nature of these relations over time.

Background: Previous studies have suggested that the Pro-Kin visual feedback balance system can promote the recovery of balance function in stroke patients.

Objectives: However, this system has not been used effectively in the early stages of stroke rehabilitation. This study aimed to investigate the effect of Pro-Kin system combined with weight loss system for the early recovery of balance and walking ability following a stroke.

Methods: A total of 62 patients who underwent radiological diagnosis of stroke were randomly divided into two groups: a control group (n = 31) and a treatment group (n = 31). Both groups received conventional balance training. The treatment group also received training on the Pro-Kin system in conjunction with a weight loss system. Balance was measured using the Berg Balance Scale (BBS), Timed 'Up & Go' (TUG) test and Pro-Kin system. Walking ability was assessed using the Functional Ambulation Classification (FAC). The tests were performed before the start of treatment and on the 4th week following the training. There was no statistically significant difference between the groups before training.

Results: After 4 weeks of training in both groups, there were significant improvements in balance and walking ability. BBS values and FAC were significantly higher (p < 0.01), TUG times, ellipse area and motion trajectory length were significantly reduced (p < 0.01, p < 0.05) after training. The treatment group outperformed the control group (p < 0.05). In addition, there was a positive correlation between balance function and walking ability (p < 0.01).

Conclusion: The Pro-Kin system combined with weight loss system is a viable method that promotes early reconstruction of balance and walking ability following a stroke.

Trial registration: Clinical trial number ChiCTR1900026370. https://www.chictr.org.cn/showprojEN.html?proj=43736.

Background: Although often asymptomatic, patent foramen ovale (PFO) may cause disabling migraine symptoms. Evidence regarding PFO closure for prevention of migraine is still ambiguous and conflicting.

Objectives: This study aims to analyze the efficacy and safety of PFO closure for mitigating migraine symptoms.

Design: This is a systematic review and meta-analysis of randomized clinical trials (RCTs) and observational studies.

Data sources and methods: A comprehensive search was conducted on the Scopus, Medline, ClinicalTrials.gov, and Cochrane Library databases up until March 12, 2024. This review incorporates literature that examines the comparison between PFO closure and control with outcome data related to migraine. We employed random-effect models to analyze the standardized mean difference (SMD) and odds ratio (OR) for presentation of the outcomes.

Results: A total of five RCTs and six observational studies were incorporated. The results of our meta-analysis showed higher reduction of monthly migraine attacks from baseline (SMD -0.34; 95% CI: -0.51, -0.18, p < 0.0001, I ² = 19%) and monthly migraine days from baseline (SMD -0.30; 95% CI: -0.53, -0.08, p = 0.009, I ² = 0%) among PFO closure than control. However, the complete resolution of migraine (especially based on the evidence from RCTs; p = 0.24), HIT-6 score (p = 0.08), and MIDAS score (p = 0.15) did not differ significantly between two groups of intervention. The majority of adverse events reported were atrial fibrillation and access site infection/bleeding that only occurred in small proportions of patients (⩽5%).

Conclusion: This study suggests better efficacy of PFO closure in reducing monthly migraine attacks and days with similar safety profile when compared to control.

Registration: PROSPERO (CRD42023453635).

Background: Epilepsy is a chronic neurological disorder characterized by recurrent seizures that significantly impact patients' quality of life. Identifying predictors is crucial for early intervention.

Objective: Electroencephalography (EEG) microstates effectively describe the resting state activity of the human brain using multichannel EEG. This study aims to develop a comprehensive prediction model that integrates clinical features with EEG microstates to predict drug-refractory epilepsy (DRE).

Design: Retrospective study.

Methods: This study encompassed 226 patients with epilepsy treated at the epilepsy center of a tertiary hospital between October 2020 and May 2023. Patients were categorized into DRE and non-DRE groups. All patients were randomly divided into training and testing sets. Lasso regression combined with Stepglm [both] algorithms was used to screen independent risk factors for DRE. These risk factors were used to construct models to predict the DRE. Three models were constructed: a clinical feature model, an EEG microstate model, and a comprehensive prediction model (combining clinical-EEG microstates). A series of evaluation methods was used to validate the accuracy and reliability of the prediction models. Finally, these models were visualized for display.

Results: In the training and testing sets, the comprehensive prediction model achieved the highest area under the curve values, registering 0.99 and 0.969, respectively. It was significantly superior to other models in terms of the C-index, with scores of 0.990 and 0.969, respectively. Additionally, the model recorded the lowest Brier scores of 0.034 and 0.071, respectively, and the calibration curve demonstrated good consistency between the predicted probabilities and observed outcomes. Decision curve analysis revealed that the model provided significant clinical net benefit across the threshold range, underscoring its strong clinical applicability. We visualized the comprehensive prediction model by developing a nomogram and established a user-friendly website to enable easy application of this model (https://fydxh.shinyapps.io/CE_model_of_DRE/).

Conclusion: A comprehensive prediction model for DRE was developed, showing excellent discrimination and calibration in both the training and testing sets. This model provided an intuitive approach for assessing the risk of developing DRE in patients with epilepsy.

Background: Among the currently approved antiobesity medications, the glucagon-like-peptide-1 receptor-agonists (GLP-1 RAs) liraglutide and semaglutide, and the dual glucose-dependent-insulinotropic-polypeptide (GIP)/GLP-1 RA tirzepatide have been suggested to reduce cardiovascular-risk in overweight or obesity without diabetes.

Objectives: The objective of this study was to evaluate the cardio- and neuroprotective potential of these novel agents in the nondiabetic overweight/obese adult population.

Data sources and methods: A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was performed to estimate the risk of major adverse cardiovascular events (MACE), all-cause and cardiovascular mortality in overweight or obese adults without diabetes treated with GLP-1 or GIP/GLP-1 RAs (vs placebo). Secondary outcomes included the risk of myocardial infarction (MI) and stroke.

Results: Sixteen RCTs (13 and 3 on GLP-1 RAs and tirzepatide, respectively) comprising 28,168 participants were included. GLP-1 or GIP/GLP-1 RAs reduced MACE (odds ratio (OR): 0.79; 95% confidence interval (CI): 0.71-0.89; p < 0.01; I ² = 0) and all-cause mortality (OR: 0.80; 95% CI: 0.70-0.92; p < 0.01; I ² = 0), while there was a trend toward lower cardiovascular-mortality (OR: 0.84; 95% CI: 0.71-1.01; p = 0.06; I ² = 0%) compared to placebo. Additionally, GLP-1 or GIP/GLP-1 RAs reduced the odds of MI (OR: 0.72; 95% CI: 0.61-0.86; p < 0.01; I ² = 0%) and nonfatal-MI (OR: 0.72; 95% CI: 0.61-0.85; p < 0.01; I ² = 0%); while no associations between antiobesity treatment and fatal-MI, stroke, nonfatal, or fatal stroke were uncovered.

Conclusion: GLP-1 and GIP/GLP-1 RAs reduce cardiovascular-risk and all-cause mortality in overweight or obese adults without diabetes. Additionally, GLP-1 RAs and GIP/GLP-1 RAs attenuate the risk of MI. Since data on stroke are still limited, future RCTs are warranted to evaluate the neuroprotective potential of these novel antiobesity agents.

Trial registration: PROSPERO CRD42024515966.

Background: Drug-resistant epilepsy (DRE) affects approximately one-third of epilepsy patients who do not achieve adequate seizure control with medication. Vagus nerve stimulation (VNS) is an adjunctive therapy for DRE, but its long-term effects on cortical excitability remain unclear.

Objectives: This study aims to elucidate the long-term effects of VNS on electroencephalography (EEG) aperiodic components in patients with DRE. Our objective is to identify biomarkers that can serve as indicators of therapeutic efficacy and provide mechanistic insights into the underlying neural processes.

Design: This longitudinal observational study focused on patients with DRE undergoing VNS therapy at Sanbo Brain Hospital. The reduction in seizure frequency rates was quantified over short-term (⩽1 year), medium-term (1-3 years), and long-term (⩾3 years) intervals to assess the therapeutic efficacy of VNS. Both the periodic and aperiodic components of EEG data were analyzed.

Methods: Advanced signal processing techniques were utilized to parameterize the periodic and aperiodic components of EEG data, focusing particularly on "offset" and "exponent." These measures were compared before and after VNS therapy. Correlation analyses were conducted to explore the relationship between these EEG parameters and clinical outcomes.

Results: In all, 18 patients with DRE participated in this study. During the long-term follow-up period, the responder rate was 55.56%. Significant decreases were observed in aperiodic offset (p = 0.022) and exponent (p = 0.039) among responders. The impact of age on these results was not significant. Correlation analyses revealed a negative association between therapeutic efficacy and a decrease in offset (R = -0.546, p = 0.019) and exponent (R = -0.636, p = 0.019).

Conclusion: EEG aperiodic parameters, including offset and exponent, have the potential to serve as promising biomarkers for evaluating the efficacy of VNS. An understanding of the regulatory influence of VNS on cortical excitability through these aperiodic parameters could provide a basis for the development of more effective stimulation parameters and therapeutic strategies.

Background: The inpatient Parkinson's Disease Multimodal Complex Treatment (PD-MCT) is an important therapeutical approach to improving gait and activities of daily living (ADL) of people with PD (PwP). Wearable device-based parameters (DBP) are new options for specific gait analyses toward individualized treatments.

Objectives: We sought to identify predictors of perceived ADL benefit taking clinical scores and DBP into account. Additionally, we analyzed DBP and clinical scores before and after PD-MCT.

Design: Exploratory observational cohort study.

Methods: Clinical scores and DBP of 56 PwP (mean age: 66.3 years, median Hoehn and Yahr (H&Y) stage: 2.5) were examined at the start and the end of a 14-day inpatient PD-MCT in a German University Medical Center. Participants performed four straight walking tasks under single- and dual-task conditions for gait analyses. Additionally, clinical scores of motor and nonmotor functions and quality of life (QoL) were assessed. Using dichotomized data of change in Movement Disorders Society Unified Parkinson's Disease Rating Scale Part II (MDS-UPDRS II) as a dependent variable and clinical and DBP as independent variables, a binomial logistic regression model was implemented.

Results: Young age, high perceived ADL impairment at baseline, high dexterity skills, and a steady gait were significant predictors of ADL benefit after PD-MCT. DBP like gait speed, number of steps, step time, stance time, and double limb support time were improved after PD-MCT. In addition, motor functions (e.g., MDS-UPDRS III and IV), QoL, perceived ADL (MDS-UPDRS II), and experience of nonmotor functions (MDS-UPDRS I) improved significantly.

Conclusion: The logistic regression model identified a group of PwP who had the most probable perceived ADL benefit after PD-MCT. Additionally, gait improved toward a faster and more dynamic gait. Using wearable technology in context of PD-MCT is promising to offer more personalized therapeutical concepts.

Trial registration: German Clinical Trial Register, https://drks.de; DRKS00020948 number, 30 March 2020, retrospectively registered.

Background: Multiple lines of evidence suggest a role of inflammation in epilepsy. Seizure incidence in patients with multiple sclerosis (MS) is twofold to threefold higher than the age-matched general population.

Objectives: To explore the association of MS disease-modifying therapies (DMTs) and FDA-approved Bruton tyrosine kinase inhibitors (for lymphocytic malignancies) with the occurrence of epilepsy using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Design: Secondary analysis of the FAERS database.

Methods: We conducted a disproportionality analysis of FAERS between 2003-Q4 and 2023-Q3. MS DMTs and the Bruton tyrosine kinase inhibitor, ibrutinib, were included in the analysis. An inverse association was defined by a 95% confidence interval (CI) upper limit of reporting odds ratio (ROR) <1.

Results: We found an inverse association of ibrutinib, ocrelizumab, ofatumumab, rituximab, and teriflunomide with epilepsy. The strongest inverse association was seen with ibrutinib (ROR: 0.338; 95% CI: 0.218-0.524).

Conclusion: Our findings suggest the possibility of considering these medications for repurposing opportunities in epilepsy and support a potential pathogenic role of leukocyte subsets in seizure perpetuation.