Neurology and Therapy最新文献

Introduction: Patients with epilepsy (PWE) face an elevated risk of osteoporosis and bone fractures. This study aims to elucidate bone metabolic alterations in PWE and identify early detection biomarkers and contributing factors.

Methods: This cross-sectional study analyzed PWE from the Epilepsy Clinical database stratified by anti seizure medication (ASM) exposure duration. We analyzed bone turnover markers (BTMs), including 25-hydroxy vitamin D, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), β-crosslaps (β-CTX) and β-CTX/OC ratio. The effects of epilepsy and ASMs on bone metabolism were analyzed by XGBoost model and SHapley Additive exPlanations (SHAP). Finally, we analyzed the mediation analyses assessing inflammatory pathway contributions.

Results: A total of 476 PWE were included in this study. Compared to ASM-naïve PWE, those receiving > 2 years of ASM therapy exhibited a reduced β-CTX/OC ratio (p = 0.002), while P1NP levels declined only after > 10 years of treatment (p < 0.001). Longitudinal data revealed a continued annual decline in the β-CTX/OC ratio during the 2-year follow-up period. After adjusting for confounders, longer ASM exposure duration was significantly correlated with decreased P1NP, β-CTX and β-CTX/OC ratio levels (β = - 1.74, 95% CI - 2.56 to - 0.92; p < 0.001). XGBoost-SHAP analysis identified valproic acid (VPA), oxcarbazepine (OXC) and history of status epilepticus as key contributors to β-CTX/OC ratio variability. Polytherapy had a more pronounced effect than monotherapy, particularly when levetiracetam was combined with VPA or OXC. Mediation analysis demonstrated that platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio mediate epilepsy/ASM-related bone metabolic alterations.

Conclusion: PWE exhibit dynamic bone metabolic alterations. Following > 2 years of ASM therapy, osteoclast inhibition precedes the onset of osteoblast dysfunction. Prolonged ASM exposure eventually reduces bone formation markers, indicating progressive impairment of osteoblastic function and a concomitant decline in bone-forming capacity. Consequently, the β-CTX/OC ratio represents a pivotal early biomarker for monitoring bone health deterioration, demonstrating significant clinical utility.

Introduction: Fingolimod (Gilenya^®), commonly used for relapsing-remitting multiple sclerosis (RRMS), is the first approved oral immunomodulatory agent. While its primary mechanism involves lymphocyte sequestration in lymphoid tissues, emerging studies report a potential link between fingolimod therapy and retinal vascular complications such as central serous chorioretinopathy and macular oedema. This study aims to describe the novel evidence on retinal aneurysmal alterations in patients receiving fingolimod, exploring possible mechanisms and clinical implications.

Methods: Case series of five eyes of five patients with retinal aneurysmal alterations and in therapy with fingolimod for multiple sclerosis. Multimodal imaging scans and medical records of patients on fingolimod therapy were reviewed. Outcome measures included best-corrected visual acuity (BCVA), central subfield thickness (CST) on spectral-domain optical coherence tomography (SD-OCT), presence of retinal aneurysmal alterations and analysis of their change in appearance over time using OCT angiography (OCTA).

Results: Findings indicate a possible association between fingolimod therapy and unilateral retinal aneurysmal changes in certain patients. The proposed mechanisms include endothelial retinal dysfunction, altered retinal vascular permeability and immune modulation effects. The clinical significance of these changes remains uncertain, necessitating further investigation.

Conclusions: Fingolimod may contribute to unilateral retinal aneurysmal vascular changes in a subset of patients. Clinicians should remain vigilant for potential retinal vascular complications, and further research is needed to clarify the underlying mechanisms, the evolution and the long-term risks associated with fingolimod therapy. Notably, in the reported cases, the retinal aneurysmal alterations showed regression following the discontinuation of fingolimod, suggesting a potential reversibility of these changes upon cessation of treatment.

Introduction: The impact of acute alcohol consumption at the onset of spontaneous non-traumatic intracerebral hemorrhage (ICH) remains unclear. We evaluated the association between elevated blood alcohol concentration (BAC) at admission and clinical outcomes in patients with ICH.

Methods: This retrospective single-center cohort study analyzed 1081 patients admitted with ICH between 2000 and 2023. BAC was measured at admission when alcohol use was suspected. Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and the Glasgow Coma Scale (GCS). Outcomes-7-day neurological deterioration (ND), mortality, 90-day modified Rankin Scale (mRS) scores-were analyzed using logistic and Cox regression models to assess associations with acute alcohol consumption.

Results: Patients that were BAC positive (alcohol group; n = 31, 2.9%) were younger, predominantly male, had larger hematoma volumes, showed significantly higher rates of 7-day ND (58.1% vs. 27.6%, p < 0.001) and mortality at 7, 30, and 90 days (51.6% vs. 23.7%, 71% vs. 37.6%, 71% vs. 43.3%, all p < 0.001) than patients with no clinical suspicion of alcohol consumption (control group; n = 1050, 97.1%). Multivariable Cox regression identified elevated BAC as an independent predictor of mortality at all time points (HR 2.089, 95% CI 1.091-3.997, p = 0.026 at 7 days; HR 2.133, 95% CI 1.220-3.728, p = 0.008 at 30 days; HR 2.096, 95% CI 1.214-3.622, p = 0.008 at 90 days). Multivariate logistic regression identified elevated BAC as an independent predictor of 7-day ND (OR 4.188, 95% CI 1.163-15.078, p = 0.028) and large ICH volume (≥ 30 cm³) (OR 3.67, 95% CI 1.388-9.704, p = 0.009). In a subgroup analysis of heavy-drinking patients, elevated BAC was associated with early ND, increased mortality, and large ICH volume.

Conclusion: Elevated BAC at ICH onset independently predicts early ND and increased mortality, indicating a potentially modifiable prognostic factor in acute ICH. These results underscore the importance of BAC measurement in patients with suspected alcohol consumption and warrant further research aimed at understanding and mitigating its potential detrimental effects.

Introduction: Cortico-subcortical dysfunction from dopaminergic depletion is a hallmark of Parkinson's disease (PD). Modulating primary motor cortex (M1) excitability with intermittent theta burst stimulation (iTBS) may restore network integrity in PD by targeting neurobiological changes at excitatory, structural, and serological levels. This study aimed to demonstrate the clinical and neurobiological effects of bilateral M1 iTBS in patients with PD.

Methods: Seventeen patients with Hoehn-Yahr stage II-III PD in the on-medication state underwent daily bilateral M1 iTBS sessions for 5 consecutive days in a randomized, double-blind, placebo-controlled, crossover design. The primary clinical outcomes were the relative change from baseline at four follow-up points after the final iTBS session, measured by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II, III, and IV. Changes in corticospinal excitability, structural brain imaging, and serum biomarkers of neurodegeneration, astrocytic activation, and neuroplasticity were also assessed.

Results: Real iTBS induced a significant improvement in MDS-UPDRS Part III scores, yielding more than twice the therapeutic benefit observed with sham stimulation. Responders (> 20% improvement) showed a mean 9-point improvement. Similarly, real iTBS stimulation resulted in an increase in corticospinal excitability of the clinically most affected hemisphere. In responders, serum brain-derived neurotrophic factor levels increased along with an increase in left ventral diencephalon volume, which was the strongest predictor of clinical response.

Conclusion: Bilateral M1 iTBS may represent a valuable adjunctive therapeutic option for pharmacological treatment of motor symptoms in patients with PD by promoting structural brain changes and enhancing synaptic plasticity in intermediate disease stages.

Clinical trial registration: https://clinicaltrials.gov/ : NCT06840145, retrospectively registered on September 9, 2023.

Introduction: Spinal cord injury (SCI), both traumatic and non-traumatic, represents a substantial global health burden, with varying incidence and mortality rates. Despite the availability of multiple data collection tools, there is no standardized, comprehensive instrument addressing the full spectrum of SCI for epidemiologic research. This project introduces a data set for SCI epidemiologic research, developed on the Research Electronic Data Capture (REDCap) platform, to enhance comparability and facilitate data exchange.

Methods: The data set was developed through extensive literature reviews and expert panel consultations. It integrates elements from the National SCI Registry of Iran (NSCIR-IR) for traumatic SCI and the International Spinal Cord Injury Data Sets for non-traumatic SCI. Modifications were made to ensure comprehensive coverage and adaptability for epidemiologic studies. The REDCap platform was utilized for its flow-based data entry design, enhancing usability and relevance.

Results: The finalized instrument contains 78 variables spanning demographics, injury characteristics, hospitalization data, medical history, interventions, and patient outcomes. It incorporates flow-based logic to streamline data entry and accommodate the specific needs of both traumatic and non-traumatic SCI cases. The data set is available for online use in the REDCap Shared Library.

Conclusion: This standardized, modifiable data instrument fills a critical gap in SCI research, enabling consistent data collection for both traumatic and non-traumatic SCI. Its adoption can facilitate comparative analyses and inform healthcare strategies globally.

Myasthenic crisis (MC) is a potentially fatal complication of myasthenia gravis (MG), often requiring intensive care and rescue therapies such as intravenous immunoglobulin (IVIG) and corticosteroids. Efgartigimod, a neonatal Fc receptor (FcRn) antagonist, offers a novel approach by selectively reducing circulating pathogenic IgG. We describe a 77-year-old man with anti-AChR-positive generalized MG who developed a severe MC, with little response to IVIG and high-dose corticosteroids. Intravenous efgartigimod was administered as rescue therapy with rapid and sustained clinical improvement. This case supports the utility of efgartigimod in MC unresponsive to conventional therapies, including in older patients with significant comorbidities.

Introduction: Evidence directly comparing newer antiseizure medications (ASMs) is limited but crucial for guiding treatment decisions. This study compared the real-world effectiveness and tolerability of brivaracetam (BRV), lacosamide (LCM) and perampanel (PER) as add-on therapy in adults with epilepsy, applying a causal-inference extension of the COMPARE study. The aim of this approach was to overcome the limitations of standard multivariable analyses, better approximate causal effects, and reinforce the credibility of the results.

Methods: Data were retrospectively collected in the Italian multicentre COMPARE study. To emulate a randomized setting, we estimated multinomial propensity scores and applied stabilized inverse probability weights. The primary analysis used a log-logistic accelerated failure time model to estimate time-to-treatment discontinuation, adjusting for adverse events (AEs), clinical response and follow-up duration. Secondary analyses evaluated changes in total and concomitant drug load and tolerability over time.

Results: Among the 850 subjects included in this analysis (259, 240 and 351 receiving LCM, BRV and PER, respectively; 53.4% female; median age 43 years), the estimated probability of 12-month retention was highest for LCM (86.1%), followed by BRV (79.1%) and PER (75.4%). Long-term trends suggested convergence of PER and LCM retention, whereas BRV discontinuation remained higher. In the adjusted analyses, BRV and PER were associated with shorter time-to-treatment discontinuation than LCM, but this negative effect decreased over time, while the beneficial effect of clinical response strengthened. Total drug load increased across all groups but remained lowest for LCM; concomitant ASM load decreased, particularly among responders. AEs were mostly mild, with dizziness, irritability and somnolence the most common AEs. AE rates were initially higher for PER and BRV, but differences diminished over time.

Conclusion: Treatment discontinuation in epilepsy emerges as a dynamic process shaped by both tolerability and clinical response. Early persistence was higher for LCM, whereas long-term retention was improved for BRV and PER. These results support a personalized approach to ASM selection that integrates early tolerability with sustained effectiveness.

Introduction: Oral corticosteroids (OCSs) and nonsteroidal immunosuppressant therapies (NSISTs) remain widely used for the clinical management of patients with generalized myasthenia gravis (gMG), despite well-documented risks. Newer targeted biologic therapies have demonstrated concomitant immunosuppressant therapy reduction; however, long-term comparative real-world evidence remains limited. This retrospective, observational study compared OCS and NSIST use in patients in the USA receiving one of the following US Food and Drug Administration-approved therapies for gMG treatment: ravulizumab or eculizumab (complement protein C5 inhibitor therapies [C5ITs]) or efgartigimod (neonatal Fc receptor antagonist).

Methods: Patients were identified using the IQVIA PharMetrics^® Plus claims database from January 1, 2015 to March 31, 2024. Eligible patients had ≥ 2 MG claims filed ≥ 30 days apart by a nonophthalmologic specialist. Treatment index date was the date of first ravulizumab, eculizumab, or efgartigimod claim. All patients assessed were continuously treated with ravulizumab, eculizumab, or efgartigimod during the 12-month follow-up period. Baseline OCS dose was estimated using claims data 3 months before the index date. Change from baseline in OCS average daily dose (ADD), OCS tapering, and NSIST use were assessed over 3-month intervals during the 12-month post-index follow-up period.

Results: After 12 months of continuous treatment, the C5IT cohort experienced a significantly greater mean reduction from baseline in OCS ADD compared to the efgartigimod cohort (C5IT, - 11.2 mg/day; efgartigimod, - 3.6 mg/day; P = 0.034), and fewer patients were taking OCS ADD > 30 mg/day (C5IT, 7.5%; efgartigimod, 22.2%). The percentage of patients with NSIST claims decreased by 28.3% within the first 12 months in the C5IT cohort (baseline, 55.2%; month 12, 39.6%) and remained stable in the efgartigimod cohort (baseline, 48.9%; month 12, 48.9%).

Conclusion: These results from US clinical practice suggest greater reductions in OCS and NSIST concomitant therapy for patients treated with ravulizumab or eculizumab compared with efgartigimod.

Alzheimer's disease (AD) remains the most common form of dementia in elderly populations. Accurately diagnosing early forms of dementia and AD remains a significant clinical challenge, especially in fast-paced primary care settings. Informant-based questionnaires that rely on close caregivers of the patients, such as the Informant Questionnaire on Cognitive Decline in the Elderly, the Ascertain Dementia 8-Item, the Quick Dementia Rating System, and the Alzheimer's Questionnaire, have recently been shown to be a valuable supplement to current standards of diagnosis, such as performance-based tests. This review aimed to explore the key characteristics of various informant-based questionnaires and evaluate their efficacy in the medical setting. Analysis of each test demonstrated that informant-based assessments show a strong ability to detect cognitive impairment early on in its pathology and can highlight gradual decline over time, compared with the single-timeframe evaluations that performance-based tests provide. Informant-based questionnaires are also able to circumvent challenges associated with the patient's education level, language, and other cultural biases, thus making them useful in diverse populations. When used in conjunction with performance tests, informant-based tests can significantly streamline the diagnostic process for dementia and enhance management and treatment strategies. Further research is advised to effectively integrate these tests into routine clinical practice and establish a new standard of care.

Introduction: While clinical trials have established the efficacy of immunoglobulin (Ig) to treat chronic inflammatory demyelinating polyneuropathy (CIDP), real-world data are limited. This study evaluated real-world effectiveness of Ig among patients with CIDP in terms of progressive use of assistive devices as a proxy for deteriorating clinical disability.

Methods: Adults diagnosed with CIDP by a neurologist from 1/2015 to 11/2021 and with a documented nerve conduction study were identified using linked medical and pharmacy claims and electronic medical record (EMR) data in the United States (US). Patients receiving Ig were propensity score matched to patients without Ig. Claims for assistive devices were used as a proxy for disability and assessed over 6-month baseline and follow-up periods. Deterioration was defined as ≥ 1 post-index claim for an assistive device indicating a higher level of disability than observed at baseline. Changes in anticonvulsant, antidepressant, and opioid use were assessed as secondary outcomes.

Results: The study sample comprised 1302 Ig-treated and non-Ig-treated matched pairs (mean age 61 years and ~ 40% female). Approximately 40% fewer Ig-treated patients had ≥ 1 level of deterioration (3.3% vs. 5.4%, p = 0.0104) and ≥ 2 levels of deterioration (3.1% vs. 5.1%, p = 0.0079) in assistive device use. Anticonvulsant (48.0-44.8%) and opioid use (39.2-33.3%; both p < 0.0001) decreased from baseline to follow-up in Ig-treated patients but remained unchanged for non-Ig-treated patients. Among patients with baseline opioid use, a higher proportion of Ig-treated patients had opioid improvement over the post-index period (41.5% vs. 32.1%, p = 0.0021).

Conclusion: Our findings support the effectiveness of Ig therapy in CIDP. The benefits of Ig seen in clinical trials of maintained or improved disability scores appear to be reflected in the real world by less deterioration in assistive device use and lesser use of anticonvulsants, antidepressants, and opioids.