Chronic inflammatory demyelinating polyneuropathy (CIDP) presents with substantial phenotypic heterogeneity, yet current classifications do not adequately capture clinically meaningful subgroups. Thus, we aimed to discover novel, clinically meaningful CIDP subgroups using unbiased clustering. In this observational, multicenter retrospective cohort study we screened 425 patients diagnosed with typical CIDP or CIDP variants from 10 German centers. Standardized data including demographic, clinical, electrophysiological, laboratory, comorbidity, and treatment information were collected. 325 patients were then randomly assigned to the discovery cohort and 100 to the validation cohort. We performed unbiased clustering and post-hoc analysis to identify clusters and define subtypes. Four distinct clusters showed marked differences: Post hoc analyses showed marked differences in disease progression and therapeutic strategies, with clusters 1 and 4 showing particularly high rates of progression and disability. Unbiased clustering revealed four clinically meaningful CIDP subtypes, each exhibiting distinct presentations and trajectories. We identified two red flag subgroups suggesting that CIDP comprises biologically and clinically heterogeneous disease phenotypes. These findings may support more individualized monitoring and therapeutic strategies for high-risk patients and raise the possibility of distinct underlying pathomechanisms across CIDP subgroups.
Post-dural puncture headache (PDPH) is a common complication of lumbar puncture caused by cerebrospinal fluid leakage and intracranial hypotension. Epidural blood patch (EBP) is considered the gold standard treatment but remains invasive. Sphenopalatine ganglion block (SPGB), a non-invasive technique, has shown promising results in recent studies, but it was not evaluated as an alternative of EBP. This study aimed to evaluate the effectiveness of SPGB in PDPH by determining whether it could reduce the need for EBP in clinical practice. We conducted a prospective monocentric cohort study including patients meeting ICHD-3 criteria for PDPH with significant pain or functional impairment. SPGB was performed using lidocaine 5
Whether donepezil exerts long-term efficacy in mitigating cognitive decline, preserving brain structure, and restoring impaired structural covariance networks in patients with mild cognitive impairment due to Alzheimer′s disease (AD-MCI) remains controversial. This study aimed to characterize the longitudinal dynamic alterations in cognition, brain morphology, and structural covariance network topology in AD-MCI patients receiving continuous 36-month donepezil treatment, thereby elucidating the long-term modulatory effects of donepezil on AD progression. Cross-sectional analysis included 92 normal controls (NC) and 107 AD-MCI patients to identify baseline abnormalitiesin cognitive performance, brain morphological parameters, global topological features, and nodal metrics of individual gray matter covariance networks. Subsequently, 35 AD-MCI patients who completed 36-month continuous donepezil treatment were retrospectively enrolled to explore the therapeutic modulation of donepezil on the aforementioned abnormal indicators. Linear and piecewise linear mixed-effects models were employed to quantify longitudinal changes. AD-MCI patients showed left hippocampus (including subfields) atrophy and widespread structural covariance network impairment at baseline. During treatment, significant time main effects were observed in MMSE scores and the volume of the left hippocampus and multiple subfields, both of which continued to show progressive decline, with accelerated deterioration between 12 and 18 months. Global topological metrics stabilized after initial short-term improvement, while right hippocampus nodal metrics were significantly enhanced. Donepezil treatment in AD-MCI patients represents a dynamic therapeutic process: it elicits transient short-term improvement of global brain network topology but confers only modest long-term benefits, with insufficient evidence supporting sustained, impactful neuroprotective effects. This study provides novel multi-level longitudinal evidence describing the neuroimaging changes underlying donepezil's modulation of AD progression.
Cladribine is regarded highly efficacious in relapsing–remitting multiple sclerosis (RRMS). However, prediction of treatment response and optimal management remain elusive, particularly during long-term. We screened the Danish Multiple Sclerosis Registry for patients with RRMS who received ≥2 5-day treatment cycles of cladribine and were followed for >90 days. Annualised relapse rates (ARR) and activity parameters (relapses or MRI activity) were analysed from 90 days after the first dose (index) to year 3 (short-term) together with time-to-first 24-week confirmed disability worsening (CDW), CDW independent of relapses (PIRA), and activity/CDW (loss of “no evidence of disease activity”, NEDA-3). Kaplan–Meier log-rank tests were validated in a subgroup who completed ≥4 five-day cladribine cycles before year 3 and contributed with >3 years follow-up (3YFS). Predicting covariables included age (< /≥ 45 years), pre-baseline activity, and short-term NEDA-3 status regarding 3YFS outcomes beyond year 3 (long-term). ARR declined significantly from 0.55 in the year pre-baseline to 0.23–0.25 from index to year 3. Younger age and pre-baseline activity predicted more frequent short-term activity. Pre-baseline activity additionally predicted short-term NEDA-3 loss. Short-term findings were consistent in 3YFS patients. CDW and PIRA were rare during short-term ( 10
To gather expert consensus regarding initiation of monoclonal high-efficacy therapies (HET) amongst treatment-naïve relapsing-remitting multiple sclerosis (RRMS) patients in France. The study leveraged the Delphi method to gauge consensus amongst an expert panel of 31 neurologists. Eight clinical cases with demographic, clinical and imaging characteristics were presented, prompting the experts to respond if they would recommend monoclonal HET. Additionally, potentially influential parameters were changed one at a time to assess whether the experts would recommend monoclonal HET. After a first round, an e-workshop was conducted to discuss non-consensual statements, which were re-submitted for rating (Round 2). Characteristics influencing monoclonal HET initiation were evaluated. 31/31 experts responded to both rounds. Consensus for or against monoclonal HET was reached for 89/108 (82.4
