Background: Interferon-beta (IFN-β) still plays a fundamental role in immunomodulation of people with multiple sclerosis (MS) with low disease activity and in clinically isolated syndrome (CIS). In 2014, pegylated (PEG) interferon was licensed by the European Medicines Agency (EMA) for relapsing-remitting MS (RRMS), enabling a lower dosing frequency.
Objectives: Our retrospective study compares laboratory findings and adverse events between subcutaneous (sc.) PEG-IFN-β-1a and IFN-β-1a in RRMS and CIS patients.
Design: Patients with CIS or RRMS fulfilling the revised McDonald criteria from 2017 visiting the neurology department of the University Medical Center of the Johannes Gutenberg University Mainz from 2010 to 2019 and treated with sc. PEG-IFN-β-1a or sc. IFN-β-1a (n = 202) were screened for eligibility. Patients who underwent regular laboratory controls in-house were included in our analysis (n = 128).
Methods: We evaluate disease progression through clinical examination, relapse history, and magnetic resonance imaging (MRI) disease activity (gadolinium-enhancing or new T2 lesions). Relevant laboratory findings such as leukopenia (leukocyte count < 3.5/nl) and neutropenia (neutrophil count <43% of lymphocytes or <1500/µl) were assessed. Telephone interviews evaluated the side effects of the respective medication. A subgroup of patients was analyzed regarding neutrophil quantities and qualities.
Results: Patients treated with sc. PEG-IFN-β-1a had significantly lower leukocyte counts (p = 0.046) and higher incidences of leukopenia (p = 0.006) and neutropenia (p = 0.03) compared to sc. IFN-β-1a. Clinical and MRI disease activity showed no significant differences, but people treated with sc. PEG-IFN-β-1a reported more common adverse events such as joint/muscle pain, injection-site reaction, and infections. No serious adverse events were reported.
Conclusion: Treatment with sc. PEG-IFN-β-1a compared to unpegylated sc. IFN-β resulted in a significantly greater reduction in leukocyte and neutrophil levels with a higher incidence of side effects. We suggest mandatory monitoring of differential blood counts before and during treatment.
Background: Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system affecting approximately 2.8 million people worldwide. In addition to genetic and environmental factors, various lifestyle factors contribute to disease development and progression.
Objectives: We performed a monocentric retrospective study and investigated the effect of lifestyle factors such as obesity, smoking, alcohol consumption, physical activity, and dietary habits on the degree of disability in a cohort of people with MS (pwMS) with an average onset of disease after the age of 55.
Design: This late-onset MS (LOMS) study group (n = 47) was characterized by a mean age of 60.9 years and a mean duration of disease of 5.0 years. The LOMS study group was compared with two control groups. The study participants in the "old control group" (Cold) were on average as old and in the "young control group" (Cyoung) as long suffering from MS as the pwMS in the LOMS group.
Methods: Data from medical documentation and a questionnaire were analyzed using descriptive frequency analyses and testing for correlation between different variables also by generalized estimating equations. The Expanded Disabilty Status Scale (EDSS) score and the progression index were used as a measure of disability.
Results: We found a significant association between smoking history and the current EDSS score in the Cyoung group, but not in the two older study groups. For physical activity, there was a significant negative correlation with EDSS score in the study group and the Cold group, alcoholic beverage consumption correlated with decreased EDSS in the Cold group. The intake of meat negatively correlated with the progression index in the LOMS group.
Conclusion: In summary, different life-style factors correlated with disability depending on patient age and disease duration. These life-style factors may be considered in the future counseling of pwMS at older ages.
Background: The predictors of intracranial haemorrhagic transformation (HT) in acute ischaemic stroke (AIS) patients undergoing dual antiplatelet therapy (DAPT) are not well known.
Objectives: The aim of this study is to identify the possible clinical and radiological predictors of HT in patients, irrespective of clinical indication for this treatment.
Design: This study is a monocentric cohort retrospective study.
Methods: We enrolled consecutive AIS patients, from our prospective register, admitted to Stroke Unit between June 2021 and June 2023 undergoing DAPT with Acetylsalicylic Acid and Clopidogrel within 72 h from symptoms onset. According to current guidelines, DAPT indication was for patients with a minor stroke, symptomatic intracranial artery stenosis and carotid angioplasty stenting. We collected clinical, demographical and radiological data. We used ABC/2 method to measure stroke volume in magnetic resonance imaging (MRI)/Diffusion-weighted imaging (DWI) sequences performed within 48 h. The primary outcome was the presence of HT at non-contrast brain computed tomography, performed 7 days after commencing DAPT.
Results: One hundred ninety-four patients were included. Twenty-eight (14.4%) presented HT. Higher NIH Stroke Scale (NIHSS) and MRI/DWI lesion volume related to increased risk of HT (p < 0.001). Reperfusion therapy and mechanical thrombectomy (MT), stent placement and a loading dose (LD) of dual antiplatelet or Clopidogrel were associated with a higher occurrence of HT (p < 0.05). Furthermore, we individuated an NIHSS cut-off value >4 (area under the curve (AUC) 0.80, sensitivity 0.82, specificity 0.65) and a volume cut-off value >8.2 ml (AUC 0.82, sensitivity 0.79, specificity 0.80) associated with an increased risk of HT (respectively, adjusted odds ratio (adj. OR) 6.5, confidence interval (CI) 1.3-32.7, p = 0.024 and adj. OR 11.0, CI 3.1-39.2, p < 0.001).
Conclusion: In clinical practice, MT treatment, antiplatelet LD administration, stent placement and clinical severity may relate to a higher risk of HT in patients with AIS and DAPT in the acute phase. In particular, we found that lesion volume cut-off could help to identify patients at greater risk of HT, regardless of the indication for DAPT.
Recent advances in multiple sclerosis (MS) management have shifted perspectives on treatment strategies, advocating for the early initiation of high-efficacy disease-modifying therapies (heDMTs). This perspective review discusses the rationale, benefits, and challenges associated with early heDMT initiation, reflecting on the obsolescence of the traditional "first-line" and "second-line" treatment classifications. The article emerges from the last update of the consensus document of the Spanish Society of Neurology on the treatment of MS. During its development, there was a recognized need to further discuss the concept of treatment lines and the early use of heDMTs. Evidence from randomized controlled trials and real-world studies suggests that early heDMT initiation leads to improved clinical outcomes, including reduced relapse rates, slowed disease progression, and decreased radiological activity, especially in younger patients or those in early disease stages. Despite the historical belief that heDMTs involve more risks and adverse events compared to moderate-efficacy DMTs (meDMTs), some studies have reported comparable safety profiles between early heDMTs and meDMTs, though long-term safety data are still lacking. The review also addresses the need for a personalized approach based on patient characteristics, prognostic factors, and preferences, explores the importance of therapeutic inertia, and highlights the evolving landscape of international and national guidelines that increasingly advocate for early intensive treatment approaches. The article also addresses the challenges of ensuring access to these therapies and the importance of further research to establish long-term safety and effectiveness of DMTs in MS.
Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes which primarily affects the sensory nervous system. Pain is the most common complaint that prompts patients to seek medical advice. With various presentations and intricate pathological mechanisms, diabetic peripheral neuropathic pain is currently the most crucial and challenging aspect of managing diabetic complications. As a heterogeneous disorder, there is no medication or treatment modality that is effective for all types of DPN and its associated neuropathic pain. Peripheral nerve decompression provides a new option for treating patients with diabetic peripheral neuropathic pain in the lower extremities. However, the clinical applicability of nerve decompression has been debated since it was first proposed. This review discusses the theoretical basis of nerve decompression, the clinical indications, and the progress of basic research based on the pathological mechanisms and nerve impairment patterns of diabetic peripheral neuropathic pain. The heterogeneity of DPN patients is summarized in terms of three aspects: complex pathophysiological mechanisms, multilevel nervous system involvement, and various nerve impairment properties. Identifying the presence of nerve entrapment among complex pathophysiological mechanisms is the key to successful outcomes. Tinel signs, focal pain, mechanical allodynia, and two-point discrimination were reported to be prognostic factors for good surgical outcomes, and their predictive ability might stem from their association with the early stage of entrapment neuropathy.
Background: Mesial temporal lobe epilepsy (MTLE) epileptiform discharges have been reported to arise from the hippocampus or the extrahippocampal medial temporal cortex, such as the amygdala, and then propagate to the temporal lobe cortex. The surgical ablation of which of these structures would result in a better postoperative outcome is debatable.
Objective: To assess the possible factors that might have influenced the postoperative outcome of a group of drug-resistant mesial MTLE patients who underwent stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RFTC).
Design: Single-center, retrospective.
Methods: The present study utilized a pre- and postoperative gray matter voxel-by-voxel ablation mapping comparison approach, along with a white matter mapping of longitudinal changes in the native space technique, to evaluate the association between the post-SEEG implantation signal recordings (obtained from clinically relevant electrode contacts used during RFTC) and the post-RFTC ablation volume of the different selected regions of interest (ROIs).
Results: The study included 22 patients (12 men and 10 women, mean age 28.86 ± 14.04 years). Sixteen patients (72.72%) were seizure-free (SF), and six patients (27.27%) were non-SF. Five patients (22.72%) experienced mild side effects following RFTC. The post-RFTC follow-up period varied from 12 to 48 months, with an average of 24.17 ± 9.86 months. The SF group was associated with a higher number of implanted electrode contacts in the amygdala that were used during RFTC, a larger preoperative volume of the amygdala; a larger ablation volume of both the amygdala and rhinal cortex. The ablation volume of the white matter was statistically similar between both groups.
Conclusion: This study provides valuable insights into the significance of the amygdala and rhinal cortex as ROIs in the preoperative evaluation of patients with MTLE. Future implantation scheme plans should consider evaluating the preoperative volume of these ROIs. Additionally, increasing the number of electrode contacts implanted within these regions might be beneficial to capture more clinically relevant signals and enhance their ablation volume.
Background: The effectiveness and safety of endovascular treatment compared with medical management alone regarding outcomes for patients with a large infarct core remain uncertain.
Objectives: To juxtapose the clinical outcomes of thrombectomy versus the best medical care in patients with a large infarct core.
Design: Systematic review and meta-analysis.
Data sources and methods: We conducted searches in PubMed, Cochrane, and Embase for articles published up until November 8, 2023. Randomized trials were selected for inclusion if they encompassed patients with large vessel occlusion and sizable strokes receiving thrombectomy. The primary outcome was functional outcomes at 3 months after pooling data using random-effects modeling. Safety outcomes included mortality at 3 months, symptomatic intracranial hemorrhage (SICH), and decompressive craniectomy. We performed a trial sequential analysis to balance type I and II errors.
Results: From 904 citations, we identified six randomized trials, involving a cohort of 1897 patients with a large ischemic region. Of these, 953 individuals underwent endovascular thrombectomy. At 3 months, thrombectomy was significantly correlated with better neurological prognosis, as evidenced by the increased odds of good functional outcomes (odds ratio (OR), 2.90; 95% confidence interval (CI), 2.08-4.05) and favorable functional outcomes (OR, 2.40; 95% CI, 1.86-3.09). Mortality rates did not demonstrably diminish as a consequence of the endovascular management (OR, 0.78; 95% CI, 0.58-1.06). However, the incidence of SICH was greater in the thrombectomy group compared to those with only medical treatment (5.5% vs 3.2%; OR, 1.77; 95% CI, 1.11-2.83). The application of trial sequential analysis yielded definitive evidence regarding favorable function outcomes and a shift in the distribution of modified Rankin scale scores at 3 months; however, others remained inconclusive.
Conclusion: The results from most of the included trials display consistency. Meta-analysis of these six randomized trials offers high-quality evidence that thrombectomy significantly mitigates disability in patients with a large infarction, while also increasing the risk of SICH.
Trial registration: PROSPERO, CRD42023480359.
Background: The diagnosis of and life-sustaining treatment (LST) for patients with disorders of consciousness (DoC) and locked-in syndrome (LIS) have been the subject of intense debate.
Objective: We aim to investigate the application of diagnostic knowledge, opinions about the administration of LST, and ethical challenges related to DoC and LIS.
Design: A cross-sectional study.
Methods: A survey was conducted among Chinese neurologists. Questionnaires included three vignettes (unresponsive wakefulness syndrome (UWS); minimally conscious state (MCS), and LIS). They were randomly distributed among neurologists from August 2018 to December 2019.
Results: A sample of 360 questionnaires was included (response rate: 78%). Overall, 63% of the participants chose the correct diagnostic category. The neurologists who received the MCS case chose the category more accurately than the neurologists with the UWS (p < 0.001) and LIS case (p = 0.002). Most neurologists preferred never to limit LST for their patients (47%, 63%, and 67% in UWS, MCS, and LIS groups, p = 0.052). A large group of neurologists believed UWS patients could feel pain (73%), with no difference from MCS and LIS patients (p > 0.05). Deciding for patients in the absence of surrogates was rated extremely challenging.
Conclusion: A large proportion of Chinese neurologists in our study didn't apply the accurate diagnostic categories to the description of DoC and LIS patients. This calls for more education and training. Most Chinese neurologists were reluctant to limit LST for patients. This may indicate that there may be a need to emphasize the allocation of more resources toward long-term care in China.
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