Search Results (20)

Background/Objectives: Cortical spreading depolarization (SD) is recognized as the pathophysiological substrate of migraine aura. Suppression of ongoing cortical activity produced by SD is thought to underlie the transient neurological deficits characteristic of the aura phase. While cortical hyperexcitability is a well-established feature of migraine brain, the effect of SD on spontaneous electrical activity in the hyperexcitable cortex remains poorly understood. Here, we investigate how SD and SD-induced depression of cortical activity are modulated by a state of mildly enhanced excitability. Methods: Using freely behaving rats, we assessed characteristics of SDs, electrocorticographic spectral power in the frontal and occipital cortices during interictal period and after SD initiation, under both drug-free conditions and following mild pharmacological disinhibition. Results: Mild cortical disinhibition resulted in a significant increase in baseline oscillatory power relative to control conditions. While cortical hyperexcitability did not alter the properties of SD itself, it differentially modulated the impact of SD on spontaneous activity in a region-specific manner. Notably, under conditions of enhanced excitability, the duration of SD-induced depression was markedly reduced in the frontal cortex but prolonged in the occipital cortex. Conclusions: These findings demonstrate that the effects of SD on spontaneous cortical activity are critically dependent on the baseline level of cortical excitability and exhibit distinct regional heterogeneity. In the awake, hyperexcitable state, the occipital cortex shows heightened vulnerability to SD-induced depression, a finding that may provide a mechanistic basis for the disproportionate involvement of the occipital cortex in aura generation and the predominance of visual symptoms in migraine aura. Full article

Background/Objectives: Self-mutilation behavior is often triggered by neuropathic pain associated with peripheral nerve injuries (PNIs). Polyethylene glycol (PEG)-fusion is a repair method that rapidly joins/fuses the open ends of closely apposed severed axons, greatly reduces Wallerian degeneration, and restores sensorimotor behavior much more rapidly than current clinical procedures. Here, we examined whether the improved sensorimotor behavior recovery following PEG-fusion repair of sciatic nerve injuries compared to Negative Controls (NC) correlated with self-mutilation. We also examined six variables (repair method, behavioral tests, sex, injury type, strain, and surgical experience) that could influence self-mutilation outcomes. Methods: The Sciatic Functional Index (SFI) and the Von Frey (VF) behavioral tests were performed and analyzed. Regression and other analyses were performed to determine the independent effect of six variables on self-mutilation rates and severity. Results: PEG-fused rats that had no self-mutilation had significantly better SFI scores than those that had self-mutilation. More rapid VF sensory recovery in PEG-fused rats was also associated with less self-mutilation. Self-mutilation rates and severity were: (1) significantly reduced following PEG-fusion repairs compared to NCs; (2) significantly increased following weekly VF tests; (3) not different between female and male rats or (4) between simple transection and segmental-loss PNIs; (5) non-existent in Lewis rats and significantly less severe in Sprague Dawley rats than Long Evans rats; and (6) significantly reduced in rats operated on by experienced PEG-fusion surgeons who historically achieved better SFI outcomes than trainee surgeons. Conclusions: Our data suggest potential clinical benefits of PEG-fusion repair to produce more rapid and better sensorimotor recoveries and reductions of self-mutilation behaviors. Full article

Background: Migraine is a highly prevalent neurological disorder associated with substantial disability and socioeconomic burden. Although pharmacological therapies remain the mainstay of treatment, their effectiveness may be limited by incomplete response and adverse effects. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a non-invasive neuromodulatory technique that may modulate cortical excitability and pain-processing networks involved in migraine pathophysiology. This systematic review aimed to evaluate the current evidence regarding the efficacy and safety of rTMS compared with sham stimulation in individuals with migraine. Methods: A systematic search was conducted in PubMed (MEDLINE), PsycNet, and Ovid (including MEDLINE and Embase) from database inception to December 2025 in accordance with PRISMA 2020 guidelines. Studies investigating rTMS in adults with migraine and including a sham comparator were eligible for inclusion. Data regarding study design, participant characteristics, rTMS parameters, outcomes, and adverse events were extracted using a predefined template. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Results: Seven studies comprising a total of 301 participants were included. Most trials evaluated high-frequency rTMS targeting the dorsolateral prefrontal cortex. Across studies, rTMS was generally associated with reductions in migraine frequency and severity compared with sham stimulation, although results varied depending on stimulation parameters and study design. Treatment was consistently well tolerated, with only mild and transient adverse effects reported. However, considerable heterogeneity was observed in diagnostic criteria, stimulation protocols, outcome measures, and follow-up duration. Conclusions: Preliminary evidence suggests that rTMS may represent a promising and well-tolerated neuromodulatory approach for migraine management. Nevertheless, methodological variability, limited sample sizes, and concerns regarding risk of bias restrict definitive conclusions. Larger randomized controlled trials with standardized protocols and longer follow-up periods are needed to clarify the clinical role of rTMS in migraine treatment. Full article

Background: Post-stroke upper-limb spasticity can cause pain, hinder passive care, and lead to secondary musculoskeletal complications. Current minimally invasive treatments have important limitations. Cryoneurolysis, which creates a controlled cold lesion of peripheral nerves, may offer a partially reversible focal denervation alternative. Methods: We conducted a feasibility case series in the outpatient department of a rehabilitation centre. Three adults with chronic post-stroke hemiparesis and a non-functional spastic upper limb underwent ultrasound- and nerve stimulation-guided cryoneurolysis of the musculocutaneous, median, and/or ulnar nerves. All had demonstrated a positive response to diagnostic nerve blocks beforehand. Feasibility outcomes included completion of planned nerve targets, tolerability under local anesthesia, absence of serious adverse events, and completion of 6-month follow-up. Secondary outcomes were Modified Ashworth Scale (MAS), qualitatively assessed passive joint mobility (video-documented), pain measured by visual analogue scale, sensory testing, and electroneuromyography (ENMG). Results: All procedures were completed as planned. Treatment was well tolerated under local anesthesia, and no serious adverse events occurred. MAS decreased by at least 2 points in targeted patterns, with immediate improvement in passive mobility; these effects persisted at 6 months. Pain remained unchanged in two participants and improved in one. Sensory testing at 6 weeks was stable. ENMG findings were heterogeneous, including reduced ulnar sensory action potential amplitude and biceps denervation activity in one participant. Conclusions: In this small series, cryoneurolysis for post-stroke upper-limb spasticity was feasible and associated with sustained tone reduction and improved passive mobility. Larger controlled studies are required to better define safety, optimize targeting strategies, and assess patient-centred outcomes. Full article

Objective: This retrospective, intention-to-treat real-world study, designed by the Greek Research Alliance for the Study of headache and Pain (GRASP) sought to compare the effectiveness and safety of anti-CGRP monoclonal antibodies (anti-CGRP Mabs) to topiramate in preventing migraine. Patients and methods: Patients received either fremanezumab, erenumab, galcanezumab, eptinezumab, or topiramate for at least six months. Outcomes included reductions in monthly headache days (MHDs), ≥50% and ≥75% responder rates, monthly acute medication intake (MAI), MHDs with peak headache intensity ≥5 on VAS, migraine-related disability (MIDAS, HIT-6), quality of life (EQ-VAS), discontinuation rates and safety. Results: We included 409 migraine patients (median age 45.2 years), predominantly female (80%) and mostly with long-standing disease and high baseline burden. After six months, all treatments reduced MHDs. Mean MHDs decreased by −7.8 days with anti-CGRP Mabs versus −3.8 days with topiramate (p < 0.001). Higher ≥50% and ≥75% responder rates were observed across all anti-CGRP agents, compared to topiramate. Anti-CGRP Mabs also achieved greater reductions in moderate/severe MHDs, MAI, disability metrics, and superior QOL gains. Among the CGRP-targeted therapies, slight differences in effectiveness outcomes were present, though failing to demonstrate any specific superiority. Safety was favorable for anti-CGRP Mabs, whereas topiramate showed substantially higher adverse events and discontinuations. Conclusions: Anti-CGRP Mabs were more effective, produced greater reductions in disability and higher improvements quality-of-life metrics and were better tolerated than topiramate. Differences among individual anti-CGRP agents were modest and unlikely to represent a clinically meaningful superiority, supporting a class-wide benefit vs. topiramate in migraine prevention both in terms of effectiveness and safety. Full article

Background: In the last few decades, microvascular decompression has been proven to be one of the best therapeutic options in the management of neurovascular compression syndromes, especially trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia. However, higher rates of recurrences and morbidities have been recorded postoperatively. In the thorough search for better solutions, the option of adjuvant QEVO^® endoscopy has arisen as a very promising alternative. Methods: In this study, a retrospective single-center observational analysis was conducted, comprising patients who underwent microvascular decompression for trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia at our institution, between January 2020 and November 2025. Demographical data and outcomes of therapeutic management were statistically analyzed and presented accordingly. Results: A total of 40 patients diagnosed with neurovascular compression syndromes were neurosurgically treated in our center, and the most common diagnosis was represented by trigeminal neuralgia, identified in 32 patients (80%). Another five (12.5%) patients underwent microvascular decompression for hemifacial spasm, two (5%) patients were treated for combined trigeminal neuralgia and hemifacial spasm, and one patient (2.5%) for glossopharyngeal neuralgia. Arterial conflict was the triggering factor in the majority of cases, and no postoperative mortality was recorded. In patients treated using adjuvant QEVO endoscopy, the identification of hidden conflicts may be facilitated. Furthermore, the use of the QEVO endoscope allowed the identification of additional neurovascular conflicts and influenced intraoperative management in a subset of patients. Conclusions: Notwithstanding the medical literature suggesting that the main influential factor for therapeutic success is the vessel type and the pattern of compression, many authors identified the cornerstone of favorable outcomes as being endoscopic assistance. Nevertheless, this adjuvant factor has had a positive impact on the majority of patients. Full article

Background: Chronic pain is a prevalent and disabling condition that affects physical health but also cognitive domains. Executive functions, including inhibitory control, cognitive flexibility, and working memory, essentials for self-regulation, treatment adherence, and coping with symptoms, are particularly compromised. Physiotherapy interventions, traditionally aimed at physical outcomes, may also influence executive functions; however, their impact remains unclear. Objective: This review aimed to synthesize current evidence regarding the effects of physiotherapy-related interventions on executive function in adults with chronic pain. Methods: The review followed the Cochrane Handbook and Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, and the protocol was registered in PROSPERO (CRD42024611800). A comprehensive search was performed. Randomized controlled trials (RCTs) included adults with chronic pain (≥3 months) whose executive function outcomes were evaluated after physiotherapy-based interventions. Results: Out of 12,391 records, 10 randomized controlled trials were included. Populations primarily had fibromyalgia, chronic low back pain, and chronic musculoskeletal pain. Interventions encompassed transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (rTMS), neurofeedback, structured exercise, and multimodal physical-cognitive-mindfulness training. Intervention durations ranged from one session to 16 weeks. Executive function was assessed with diverse neuropsychological tests. tDCS improved attention, inhibitory control, cognitive flexibility, and working memory. Exercise interventions showed benefits in working memory and inhibitory control. Conclusions: Preliminary evidence suggests that physiotherapy interventions, particularly anodal tDCS and structured exercise, may improve executive functions in individuals with chronic pain. Future trials should incorporate long-term follow-up. Integrating cognitive targets into physiotherapy may enhance the multidimensional management of chronic pain. Full article

Background/Objective: It remains unknown whether patients with the more common forms of hypermobility carry an elevated risk for the development of intracranial/cervical artery abnormalities. The objective of this study was to determine the prevalence of unruptured intracranial aneurysms, spontaneous cervical artery dissections, and fibromuscular dysplasia in patients with hypermobile Ehlers–Danlos Syndrome (hEDS) and hypermobility spectrum disorders (HSD) who presented to an academic headache clinic. Methods: This is a retrospective cohort study. We used an electronic medical record to look for all patients seen at the Mayo Clinic Florida Headache Center and EDS Clinic between 2019 and 2025 with a diagnosis of hEDS or HSD and neuroimaging of both the intracranial and cervical arteries. Results: There were 103 patients who met the inclusion criteria. There was no statistically significant difference between hEDS and HSD patients in developing cerebral/cervical arterial anomalies. Of the sample, 95% of the hypermobile patients with abnormal neuroimaging also had migraine. A total of eleven (10.7%) patients (hEDS + HSD) were diagnosed with unruptured intracranial aneurysms. Trends included age less than 50 years, small aneurysms in the anterior circulation, and having migraine with aura. Five (4.8%) patients were diagnosed with spontaneous cervical artery dissection with trends for HSD, over the age of 50 years, vertebral artery involvement and a history of migraine without aura. Six (5.8%) patients were diagnosed with fibromuscular dysplasia with trends for HSD, over the age of 50 years, carotid artery involvement and a history of migraine with aura. Conclusions: This is the first study to identify that patients with the more common type of EDS, HSD and hEDS, and a possible concomitant history of migraine have a heightened risk for the development of unruptured intracranial aneurysms, spontaneous cervical artery dissections, and fibromuscular dysplasia. Our findings suggest the need for targeted screening with intracranial and extracranial arterial imaging for this unique patient population. Full article

Background: Neuropathic pain represents a substantial global burden with limited effective therapeutic options. Pulsed Electromagnetic Field (PEMF) therapy has emerged as a potential non-invasive adjuvant, though clinical evidence remains inconsistent. This systematic review and meta-analysis evaluated PEMF efficacy and safety, specifically analyzing the influence of etiology and stimulation parameters. Methods: Following PRISMA 2020 guidelines (PROSPERO: CRD420251184151), five databases (Cochrane, PubMed, Scopus, Web of Science, and LILACS) were searched for Randomized Controlled Trials (RCTs) comparing PEMF versus sham. Risk of bias was assessed via Cochrane RoB 2, and heterogeneity was explored through detailed subgroup analyses. Results: Thirteen RCTs met the inclusion criteria (N = 688). While global analysis indicated a statistically significant pain reduction (SMD: −1.01; p = 0.03), it exhibited extreme statistical heterogeneity (I² = 92.8%) and instability. After adjusting for missing studies using the Trim-and-Fill method, global significance disappeared. However, subgroup analysis resolved this inconsistency, revealing a massive, clinically meaningful effect in Spinal/Radicular pain (SMD: −2.35; 95% CI: −4.42 to −0.29), whereas Peripheral Neuropathy showed no significant reduction (SMD: −0.38; 95% CI: −0.86 to 0.10). Conclusions: The PEMF evidence base for neuropathic pain is currently highly fragmented. Extreme heterogeneity and publication bias render “one-size-fits-all” efficacy estimates invalid and potentially misleading. Instead, our data reveals a critical etiological divergence: PEMF appears highly effective for spinal/radicular pathology, likely due to the mechanical nature of the lesion, but demonstrates limited efficacy for diffuse peripheral neuropathy. Future research must abandon generic protocols in favor of etiology-specific trials, prioritizing high-frequency parameters and rigorous bias control. Full article

Background/Objectives: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRP-mAbs) are effective injectable medications for the treatment of migraine. This study aimed to evaluate continuation, resumption, and withdrawal rates of CGRP-mAb treatment under real-world clinical conditions. Methods: Treatment-naïve patients with at least 3 months of follow-up after starting CGRP-mAb treatment were included. The decision to continue, discontinue, or resume CGRP-mAb treatment was made freely by the patients. Headache Impact Test-6 (HIT-6) and the Migraine-Specific Quality of Life Questionnaire (MSQ) were administered before starting treatment and one month after each CGRP-mAb injection. The endpoints were as follows: continuation rates of CGRP-mAb treatment after treatment initiation; resumption rate; withdrawal rate; changes in HIT-6 and MSQ scores; and differences in background factors between the resumption and withdrawal groups. Results: Of the 1162 migraine patients, 146 were included in the analysis. Continuation rates of CGRP-mAb treatment at 3, 6, 9, 12, 18, and 24 months were 93.2%, 80.2%, 68.9%, 58.8%, 55.4%, and 51.7%, respectively. For the patients who discontinued, the resumption rate was 76.8%, and the withdrawal rate was 20.7%. HIT-6 and MSQ scores were significantly decreased at all assessment points compared with before CGRP-mAb treatment. There were no significant differences in factors between the resumption and withdrawal groups. Conclusions: Under real-world clinical conditions in which patients were free to choose their own treatment, the continuation rate of CGRP-mAb treatment 12 months after treatment initiation was 58.8%, and more than half of patients remained on treatment after 24 months. The resumption rate was 76.8% and the withdrawal rate was 20.7%. Full article

Background: Migraine is a highly prevalent neurological disorder and a leading cause of disability, particularly among working-age adults. Although the Work Productivity and Activity Impairment (WPAI) questionnaire is widely used to assess the functional impact of health conditions, no validated Arabic version specific to migraine is currently available. This study was conducted to validate the Arabic version of the WPAI:Migraine questionnaire among Arabic-speaking migraine patients in Saudi Arabia. Methods: A cross-sectional psychometric validation study was conducted at a tertiary headache clinic between June 2023 and January 2024. Adult patients diagnosed with episodic or chronic migraine, based on the International Classification of Headache Disorders, 3rd edition (ICHD-3), completed the Arabic version of the WPAI:Migraine and the validated Arabic version of the Migraine Disability Assessment Scale (MIDAS). Test–retest reliability was assessed after two weeks. Psychometric properties, including reliability, criterion validity, and known-group validity, were evaluated using intraclass correlation coefficients (ICCs), Pearson’s and Spearman’s correlations, and one-way ANOVA. Results: Eighty-two patients completed the study (76.8% female; mean age 38 ± 11 years). The Arabic WPAI:Migraine questionnaire demonstrated substantial-to-almost-perfect test–retest reliability (ICC range: 0.68–0.84). WPAI:Migraine domain scores correlated significantly with MIDAS scores—particularly for activity impairment (r = 0.576), presenteeism (r = 0.526), and absenteeism (r = 0.522)—and increased consistently across MIDAS disability grades, supporting validity. Conclusions: The Arabic WPAI:Migraine questionnaire is a valid and reliable instrument for assessing work productivity and activity impairment among Arabic-speaking migraine patients, suitable for clinical and research use. Full article

Background: Pronator teres syndrome is a rare proximal median neuropathy caused by compression of the median nerve at various points. It is a rare condition, and many times it is mistaken for carpal tunnel syndrome. Methods: There are many authors who refer to the pronator syndrome as a compression of the median nerve at several potential sites of en-trapment in the region of the antecubital fossa, more proximal compression at the Liga-ment of Strutters, and more distally, including lacerus fibrosus within the pronator teres muscle and the anterior interosseous nerve. Results: The diagnostic difficulties in a patient with severe right forearm pain during elbow flexion and pronation are presented. Routine test results, including MRI of the right elbow joint, nerve conduction study of the brachial plexus and ulnar nerve, and electromyographic study of the muscles of the right upper ex-tremity, were normal. Ultrasonography showed an enlarged pronator teres muscle. Conclusions: The patient underwent surgical removal of the lacertus fibrosus. All symptoms resolved. Full article

Background: Hypothyroidism has been implicated as a risk factor for carpal tunnel syndrome (CTS). However, the effect of hypothyroidism on the risk of CTS has not been studied in large, non-selective clinic populations, and the impact of hypothyroidism on electrodiagnostic parameters remains inadequately understood. Methods: In this retrospective study, we examined 480 patients referred for upper limb electrodiagnostic evaluation. We compared the prevalence of CTS among patients with and without hypothyroidism, adjusting for age and gender. Additionally, we compared the median nerve sensory and motor latencies and comparative latency studies (COLS) [median-to-ulnar comparison through palmar difference (Palmdiff) and ring difference studies (Ringdiff); and median-to-radial comparison through a thumb difference study (Thumbdiff)] among patients with and without hypothyroidism disease, stratified by CTS status and age groups. Results: The crude prevalence of CTS was higher among patients with hypothyroidism (79.7%) compared to those without (61.8%) (p = 0.005). However, after adjusting for age and gender, logistic regression analysis revealed a non-significant association between hypothyroidism and CTS (adjusted odds ratio (OR): 1.71; 95% CI: 0.89–3.28, p = 0.106). CTS was more prevalent among patients with hypothyroidism under 50 years of age (OR: 2.59; 95% CI: 1.17–5.73, p = 0.018). There were no significant differences in any electrodiagnostic parameters between patients with and without hypothyroidism among CTS and non-CTS groups. Conclusions: Hypothyroidism increased the risk of CTS among patients under 50 years of age. The electrodiagnostic parameters used for CTS diagnosis were not influenced by the presence of hypothyroidism. Full article

Pediatric hip surgeries are associated with moderate to high levels of pain, which, in severe cases can lead to opioid prescription and use. There is a growing focus on reducing post-operative pain in these patients to decrease the need for opioids, as well as increase early mobilization for recovery. Conventional methods of pain relief using opioids can have unwanted negative impacts on pediatric patients such as respiratory depression, nausea, confusion, and the concerning possibility for the development of dependence. Likewise, traditional methods of anesthesia, like the lumbar epidural block, can have unwanted systemic side effects, such as hypotension, urinary retention, arrhythmias, and spinal abscesses. These complications can lead to longer hospital stays and delayed recovery. This review analyzes the efficacy of a newer regional anesthesia technique, the pericapsular nerve group (PENG) block, in comparison to the lumbar epidural block. This technique utilizes precision-based anesthesia to selectively block the articular branches to the hip joint while avoiding the main trunks of the femoral and obturator nerves. Additionally, with the utilization of high-resolution ultrasound to guide the blocks, providers can increasingly count on proper insertion and predictable anesthetic spread. The result is a motor-sparing blockade that shows promise in allowing earlier mobilization and better functional recovery times after pediatric hip surgeries. Full article

Cannabinoids have gained increasing attention as potential therapeutic agents in chronic pain management. Their mechanisms of action, mediated through CB1 and CB2 receptors, provide a pharmacological alternative to conventional analgesics. The evidence is strongest for neuropathic pain and multiple sclerosis-related spasticity, while the results for fibromyalgia, osteoarthritis, and musculoskeletal pain remain inconsistent. The average pain reduction is modest, often not exceeding 0.5–1.0 points on a 10-point scale, and therapeutic gains are offset by safety concerns. Quantitative data show that discontinuation rates range from 4.3% at low-dose CBD to 12.9% at high-dose CBD, compared with 3.5% on placebo, while nabiximols (THC + CBD spray) are associated with dizziness in 25% of patients, somnolence in 8%, and treatment discontinuation in 12%. High-dose CBD also carries a measurable risk of hepatotoxicity. Regulatory heterogeneity further constrains trial feasibility, scalability, and patient access, with disparities evident across the United States, Europe, Canada, and Australia. Overall, cannabinoids provide modest, condition-specific analgesia and should be considered adjunctive rather than first-line options, reserved for patients unresponsive to conventional therapy. Future progress requires standardized formulations, harmonized international regulations, long-term safety data, and large-scale randomized controlled trials to clarify their role in evidence-based pain management. Full article