Neurology and Therapy最新文献

Neurodegenerative diseases are among the most prevalent and debilitating disorders in aging populations. Despite growing insights into their complex pathophysiology, effective disease-modifying treatments remain limited. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors, primarily used in type 2 diabetes mellitus, have recently gained attention for their potential neuroprotective effects. This narrative review aims to summarize the current preclinical and clinical evidence on the impact of SGLT-2 inhibitors on neurodegenerative diseases, exploring their mechanisms of action, therapeutic potential, and limitations. The authors reviewed experimental studies, animal models, clinical trials, and observational data focusing on the potential links between SGLT-2 inhibitors and neurodegeneration. We further analyzed proposed mechanisms-including metabolic, inflammatory, and vascular factors-in the context of their potential contribution to, or consequence of, neurodegenerative processes, emphasizing their interdependence rather than treating neurodegeneration as an isolated phenomenon. Preclinical studies consistently show that SGLT-2 inhibitors reduce neuroinflammation, improve mitochondrial function, enhance insulin sensitivity in the brain, and may mitigate amyloid and tau pathology. Observational clinical data suggest a lower incidence of dementia in patients treated with SGLT-2 inhibitors. However, cognitive outcomes have not been directly assessed in major randomized trials to date. SGLT-2 inhibitors hold promise as modulators of neurodegenerative processes, but robust clinical trials with cognitive endpoints are needed to confirm their therapeutic relevance. Their potential to bridge metabolic and neurodegenerative pathways highlights a novel avenue for future research and therapeutic development.

Introduction: Generalised myasthenia gravis (gMG) is a rare autoimmune disorder presenting as variable skeletal muscle weakness and fatigue. Comorbidities are common and symptoms are unpredictable and fluctuating. Many patients rely on immunosuppressive treatments including corticosteroids in their disease management, despite adverse events (AEs) associated with extended or high-dose use. We aimed to investigate clinical characteristics, treatment patterns, and disease burden of patients diagnosed with gMG across the Asia-Pacific region.

Methods: Data were drawn from the Adelphi Real World gMG Disease Specific Programme™, a cross-sectional survey of neurologists and their patients with gMG in Australia, China, Japan, South Korea, Malaysia, and Taiwan, from July 2023 to January 2024. Neurologists reported clinical characteristics from diagnosis, current maintenance treatment initiation, and at survey completion.

Results: Neurologists (n = 173) reported data on 407 patients with gMG. At the time of survey, mean (standard deviation) patient age was 51.5 (15.3) years and 58.2% were female. Also at survey, 77.6%, 20.1%, and 2.2% of patients had a Myasthenia Gravis Foundation of America class of II, III, or IV, respectively. Since diagnosis, myasthenic crises (22.5%) or exacerbations (37.2%) were reported for most patients (52.7%). Acetylcholinesterase inhibitors (82.8%) and corticosteroids (69.5%) were most commonly prescribed gMG treatments at survey completion, and 65.1% of patients were not in pharmacological remission. AEs were experienced by 71.0% of those prescribed corticosteroids. Joint effects of corticosteroid dose and duration on the increased number of comorbidities and AEs was significant (p = 0.0319).

Conclusion: Across the Asia-Pacific, most patients did not achieve pharmacological remission despite prescribed treatments, and experienced treatment-related AEs, indicating significant unmet clinical needs. It is suggested that corticosteroid overreliance in maintenance treatment could be associated with increases in comorbidities and AEs. Further research is needed to understand how novel treatments could impact clinical outcomes and reduce corticosteroid reliance for patients with gMG in the Asia-Pacific.

Introduction: While double-filtration plasmapheresis (DFPP) and intravenously administered methylprednisolone (IVMP) are both established treatments for acute attacks of neuromyelitis optica spectrum disorder (NMOSD), their comparative efficacy and safety profiles remain a critical area of investigation. This study aimed to evaluate the clinical outcomes and adverse events of DFPP versus IVMP in patients with NMOSD, with a focus on disability improvement and treatment tolerability.

Methods: A prospective single-center cohort study was performed with 146 patients with NMOSD, who were treated with DFPP, IVMP, and combination therapy (DFPP + IVMP). Primary efficacy was measured by changes in Expanded Disability Status Scale (EDSS) scores (ΔEDSS). Secondary outcomes included Modified Rankin Scale (mRS) scores. Safety profiles, including liver enzyme elevation and infection rates, were monitored.

Results: The DFPP group (n = 81) demonstrated a significant clinical response, with a median EDSS improvement of 0.5 (IQR 0.0-1.0) points. The response rate (defined as ΔEDSS > 0) was 66.7%, with 33.3% (27/81), 18.5% (15/81), and 14.8% (12/81) of patients achieving improvements of 0.5, 1.0, and ≥ 1.5 points, respectively. This was accompanied by a marked reduction in serum immunoglobulins (IgG: 11.87 ± 4.39 to 3.13 ± 1.76 g/L, p < 0.001). The DFPP group and IVMP monotherapy group showed comparable efficacy, with 66.7% (54/81) and 69.2% (45/65) of patients achieving EDSS improvement, respectively (OR 0.89, 95% CI 0.45-1.77, p = 0.742). The magnitude of EDSS improvement was identical between groups (median ΔEDSS 0.5 points). Combination therapy demonstrated particular utility in severe cases (median baseline EDSS 5.0 [IQR 3.5-6.5]). Adverse events were fewer with DFPP than with IVMP (19.8% vs. 33.8%, p = 0.059).

Conclusion: DFPP exhibited comparable effectiveness to IVMP in improving disability during NMOSD acute attacks, with a trend towards a more favorable safety profile. The combination of DFPP and IVMP may benefit severe cases. These findings support DFPP as a viable therapeutic option, particularly for patients with high baseline disability or steroid-refractory disease.

Introduction: Dexamethasone is an effective emerging agent for the treatment of infantile epileptic spasms syndrome (IESS), which, unlike with adrenocorticotropic hormone (ACTH) and prednisolone, does not yet have a universally accepted dosing protocol. We present a novel, highly individualizable pulsed dexamethasone dosing scheme for IESS therapy.

Methods: We retrospectively analyzed data of infants with IESS treated in our center with pulsed dexamethasone: 20 mg/m²/day was given intravenously for 3 days every 1-4 weeks. Five pulses were aimed for; the final amount and interval between them were determined individually depending on the patient's seizure burden, EEG findings, and IESS etiology. Demographic, clinical, and EEG data were extracted from clinical records. Response to therapy was defined on the basis of seizure freedom and EEG findings 4 weeks after dexamethasone administration.

Results: Sixty-six infants with 57.6% male predominance were included in analysis. Mean age was 6.2 months at first seizure and 7.3 months at diagnosis. IESS etiology was unknown in 37.9%, structural in 33.3%, and genetic in 13.6% of patients, the rest being mixed. Median delay between diagnosis and treatment start was 1 day. Patients received up to 11 pulses, with the majority (47%) given 5. Seizure freedom was achieved in 81.8% of patients, 11.4 days after first pulse on average. Unknown IESS was associated with best response to therapy. Compared to poor responders, where more administered pulses mirrored IESS pharmacoresistance, fewer pulses were sufficient to achieve remission with no relapses in the 6 months following therapy end in good responders. No major side effects were observed.

Conclusion: Dexamethasone is an effective alternative to ACTH and prednisolone in IESS therapy. Our therapy regimen is effective, well tolerated, and flexible. Reflecting its potential as an individualized, patient-tailored approach, we demonstrate that fewer pulses may suffice to achieve a relapse-free remission in carefully selected patient cohorts.

Introduction: Due to recent progress in multiple sclerosis (MS) research, a range of disease-modifying therapies (DMT) is increasingly available. According to the personalized therapeutic approach, the choice of DMT for a particular patient is based on complex analysis of disease-related and drug-related aspects, with emphasis on patient's preferences and shared decision-making. The aim of this study was to evaluate the perspective of the disease and various aspects of treatment in Polish patients with MS (pwMS), with reference to sociodemographic and clinical data.

Methods: The nationwide survey was conducted, addressed to adult pwMS treated with DMT and undergoing regular follow-up in regional MS Centers. The questionnaire contained sociodemographic data, and questions about major troublesome and feared aspects of disease, and about the importance of various aspects of treatment. In addition, MS-related data were provided by neurologists. The responses have been summarized and analyzed for their relationships with sociodemographic and clinical data.

Results: A total of 2032 pwMS (70% women; mean age 42.1 ± 10.8 years) were included from 14 MS Centers. Over 90% had relapsing-remitting MS, mean disease duration was 12 years and the median Expanded Disability Status Scale (EDSS) was 2.4 ± 1.5. Fatigue (50%), limb weakness (47%), and balance and gait disturbances (30%) were the most common and troublesome symptoms reported by the respondents. Their main concerns about disease consequences included disability (46%) and dependence on others (17%). All aspects of DMT efficacy were very important for more than 70% of patients, with preventing disability progression, maintaining social participation, and reduction of relapses as top priorities (86-95%). Treatment safety concerns were focused on risk of cancer (74%), effect on comorbidities (63%), and severe infections (60%). Drug efficacy (93%), modernity (60%), and mechanism of action (59%) were most commonly indicated factors influencing patients' preference for DMT. Significant relationships were found between pwMS opinion about aspects of treatment and their age, sex, family status and vocational activity, as well as type and duration of MS, EDSS score, and type of DMT used.

Conclusion: The Polish pwMS perspective of disease is focused on emerging disability and its social context. Regarding aspects of treatment, sufferers are highly concerned about its efficacy (especially in preventing the mentioned disease consequences), followed by safety and convenience. Individual differences in patients' responses should be highlighted, associated with combined impact of demographic and clinical data. The study findings should inform complex and personalized therapeutic approaches to MS management in clinical practice.

Introduction: Embolic stroke is connected to a higher risk of hemorrhagic transformation (HT), functional disability, and mortality. There is a gap of knowledge regarding the predictors of long-term post-alteplase functional outcomes, especially in patients with atrial fibrillation (AF), which limits delivering adequate care and support to stroke survivors. We aimed to assess the predictors of long-term post-thrombolysis unfavorable functional outcomes in patients with atrial fibrillation who presented with first-ever embolic stroke in the Middle East and North Africa (MENA).

Methods: Our prospective cohort study was conducted between May 2021 and May 2025 and included patients with AF who presented with first-ever embolic stroke and received thrombolytic therapy, and who were recruited from Kafr Elsheikh University Hospital, Kafr Elsheikh General Hospital, Al-Sahel Teaching Hospital, NMC Royal Hospital, and Al-Obour Hospital in the period from May 2021 to May 2023. Our longitudinal study included two groups; the unfavorable outcomes group, and the favorable outcomes group.

Results: A total of 580 patients completed the 2-year follow-up period. National institute of health stroke scale (NIHSS) at the time of admission [odds ratio (OR), 2.06; 95% CI, 1.86-4.39; P = 0.03], sustained atrial fibrillation (OR, 1.98; 95% CI, 1.42-3.80; P = 0.03), heart failure (OR, 1.79; 95% CI, 1.23-2.96; P = 0.03), HAS-BLED score (OR, 1.64; 95% CI, 1.41-3.65; P = 0.03), CHA₂DS₂VASc score (OR, 1.72; 95% CI, 1.72-3.53; P = 0.04), post-thrombolysis intracranial hemorrhage (OR, 2.89; 95% CI, 1.74-3.63; P = 0.02), and recurrent symptomatic stroke (OR, 1.98; 95% CI, 1.22-3.73; P = 0.04) were predictors of long-term post-thrombolysis unfavorable outcomes.

Conclusion: Higher baseline NIHSS, heart failure, post-thrombolysis intracranial haemorrhage, and recurrent symptomatic stroke were independent predictors of long-term post-thrombolysis unfavorable functional outcome in embolic stroke patients. Novelly, higher HAS-BLED and CHA2DS2-VASc scores were independent predictors of long-term post-thrombolysis unfavorable functional outcome in Arabian patients. Moreover, sustained AF was an independent predictor of long-term post-thrombolysis unfavorable functional outcome.

Introduction: Ofatumumab (OFA) is a highly effective therapeutic option for multiple sclerosis (MS), but real-world data on its efficacy and safety remain limited. We evaluated the real-world efficacy and safety of OFA in patients with MS and explored the predictive value of frailty.

Methods: We retrospectively collected clinical and MRI data from 12 MS centers in Central Italy, including patients who initiated OFA between April 2022 and January 2024. We assessed annualized relapse rate (ARR), clinical relapses, radiological activity, and safety. Frailty, defined as increased vulnerability due to age-related health deficits, was measured using a frailty index (FI). The study was approved by the local Ethics Committee (No. 6357).

Results: A total of 242 patients with MS were included (66.8% female and 33.2% male; mean age: 38.9 ± 10.3 years; disease duration: 7.7 ± 7.6 years). Of these, 95 (39.2%) were treatment-naïve, and 147 (60.8%) had switched from another therapy, mostly a first switch. The mean follow-up was 15.4 ± 5.4 months; all patients completed 12-month follow-up, and 103 completed 24 months. ARR dropped from 0.9 to 0.02 (p < 0.001). Only 4 patients (1.6%) had a clinical relapse, all within 6 months (mean time: 3.0 ± 1.8 months). Expanded Disability Status Scale (EDSS) scores remained stable (p > 0.05). MRI activity occurred in 10 patients (4.1%) at 6 months and 3 (1.2%) at 12 months; none at 24 months. Adverse events included flu-like symptoms (34.3%), injection site reactions (8.2%), and infections (18.5%). Among 239 patients assessed for frailty (mean FI: 0.06 ± 0.08), 187 were relatively fit (FI ≤ 0.10), 30 least fit, and 22 frail. FI predicted 24-month confirmed disability progression (p = 0.0068), with significant variation by frailty level (p = 0.0009).

Conclusion: This real-world study suggests that OFA is effective and safe for MS, offering rapid disease control. Lower frailty levels suggest preferential use in patients with lower baseline disability. Further large-scale, long-term studies are needed.

Introduction: Generalized myasthenia gravis (gMG) is a chronic autoimmune neuromuscular disorder for which treatment decision-making is increasingly complex due to the emergence of biologic targeted therapies. This study aimed to evaluate neurologists' treatment preferences in acetylcholine receptor seropositive gMG using conjoint analysis to simulate real-world clinical decision-making.

Methods: We conducted a cross-sectional, web-based study among neurologists involved in the management of gMG in collaboration with the Spanish Society of Neurology. Participants were presented with eight hypothetical treatment scenarios comprising five key attributes: intensity of improvement, onset of action, duration of effect, adverse events, and route/frequency of administration. Utility values and importance of each attribute were estimated using ordinary least squares regression. Demographic, professional, and behavioral characteristics were assessed to explore variability in preference patterns.

Results: A total of 149 neurologists participated in the study. The mean age was 39.0 (SD 9.4) years, and 54.4% were male. Participants had a mean of 9.9 years (8.4) of experience treating patients with MG. The most valued treatment attribute was intensity of improvement (mean relative importance: 38.6%), followed by onset of action (21.5%) and duration of effect (17.4%). At the individual level, route and frequency of administration accounted for up to 21.9% of decision weight in some participants. Preferences were consistent across neuromuscular specialists and general neurologists but differed based on empathy and conscientiousness. Model fit was robust (Pearson's R = 1.000, p < 0.001).

Conclusions: Neurologists treating gMG placed the highest value on rapid and clinically meaningful symptom improvement, consistent with the therapeutic goals of emerging targeted therapies. However, substantial heterogeneity in preferences, especially regarding administration burden, emphasizes the need for individualized approaches and shared decision-making.

Introduction: Guillain-Barré syndrome (GBS) is an acute immune-mediated disorder of the peripheral nervous system, marked by rapid onset of neurological symptoms. Despite progress in understanding the etiology and improving clinical management, no validated biomarkers are currently available to predict disease severity or treatment response during the acute phase. This meta-analysis aims to evaluate the role of serum neurofilament light chain (NfL) as a biomarker of acute disease activity and prognostic outcomes in GBS.

Methods: A systematic review and meta-analysis was conducted using PubMed, Scopus, and Cochrane Library databases to identify studies assessing NfL levels in patients with GBS. In addition, we included data from our own cohort of patients with GBS-whose NfL levels were measured at disease onset-and from healthy controls. The primary outcome was the difference in NfL levels-both in serum and cerebrospinal fluid (CSF)-between patients with GBS and controls. Secondary outcomes included the correlations between acute-phase NfL levels, clinical severity at admission as measured by the Guillain-Barré Disability Scale (GBDS) or the Hughes Functional Scale (HFS), and long-term outcomes such as the inability to walk or run 1 year after disease onset.

Results: In this meta-analysis of nine studies, which also included data from our cohort, serum NfL levels were significantly higher in patients with GBS compared with controls (mean difference 143.17 pg/mL, 95% CI 67.7-218.6; p < 0.01; I² = 83%). In contrast, the difference in CSF NfL levels only approached statistical significance (mean difference 2091.1 pg/mL, 95% CI 171.2-4353.4; p = 0.07, I² = 92.1%). These findings were corroborated in our cohort, where median serum NfL concentrations were markedly higher in patients with GBS compared to controls (97 pg/mL, IQR 79-194 vs. 15 pg/mL, IQR 13-20; p < 0.05, Wilcoxon rank-sum test). Serum NfL levels were higher in patients with the acute motor axonal neuropathy (AMAN) compared to those with acute inflammatory demyelinating polyneuropathy (AIDP) (MD 531.9 pg/mL, 95% CI 32.8-1031.01; I² = 81.1%; p = 0.04). Moreover, NfL levels positively correlated with disease severity at admission (r = 0.38; p < 0.001) and poor long-term outcomes (OR 3.74, 95% CI 1.05-13.37; p < 0.001).

Conclusion: Serum NfL is a promising biomarker for early diagnosis and prognosis in GBS and may support risk stratification at hospital admission.

Introduction: Dementia with Lewy bodies (DLB), a common cause of dementia, has no FDA-approved therapies, and clinical trials to date have had limited ability to demonstrate efficacy. The lack of validated DLB-specific clinical trial outcomes may hinder these efforts. Here, we test whether the Clinical Dementia Rating (CDR) and other commonly used clinical evaluation tools for Alzheimer's disease (AD) and Parkinson's disease (PD) could potentially be used as outcome measures in future DLB clinical trials.

Methods: A retrospective, cross-sectional chart review of 600 patients (359 AD, 241 DLB) who completed a comprehensive clinical, cognitive, functional, and behavioral evaluation over a 10-year period was carried out. Performance of the CDR, its sum of boxes (CDR-SB), and other AD and PD evaluation measures were assessed for stage-wide performance from mild cognitive impairment (CDR 0.5) to moderate-severe dementia (CDR 2).

Results: The CDR and CDR-SB characterize important differences between AD and DLB across different cross-sectional stages of disease severity, with the greatest differences seen at the CDR 0.5 stage. DLB showed greater deficits in commonly used AD functional and behavioral measures at the CDR 0.5 stage, while more DLB-specific measures showed significant differences from AD across the entire disease spectrum. The patient version of the Quick Dementia Rating System showed greater stage-wide impairment in DLB than AD, supporting its use as a patient-reported outcome. The Montreal Cognitive Assessment showed greater stage-wide impairment in AD than in DLB patients, suggesting lack of sensitivity as an outcome measure for DLB clinical trials.

Conclusion: Improved study design and selection of appropriate outcome measures in DLB clinical trials can facilitate demonstration of efficacy. While the CDR-SB could work on a DLB clinical trial, the field would be most advanced by the development of a DLB-specific global rating instrument.