RSS 1.0Neurology
Recent Submissions
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The effects of adrenal insufficiency and its treatment on cognition in an athlete with post-concussion syndromePost-concussion Syndrome (PCS) describes persistent nonspecific neurological, cognitive and emotional symptoms following concussion. A young male presented to a sports concussion clinic with persistent symptoms post-injury. Neurocognitive testing found unexpected severe memory impairment. Blood tests for pituitary function returned low cortisol levels secondary to adrenal insufficiency (AI), which was immediately treated. Post-treatment and improvement of cortisol levels, repeat neuropsychology testing demonstrated reliable improvement in memory and processing speed test scores, commensurate with premorbid expectations. This case highlights the importance of a broad diagnostic approach to formulating unexpected persistent PCS symptoms, screening for AI in PCS cases, and completing neurocognitive testing.
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Implantable and transcutaneous photobiomodulation promote neuroregeneration and recovery of lost function after spinal cord injury.Spinal cord injury (SCI) is a cause of profound and irreversible damage, with no effective therapy to promote functional recovery. Photobiomodulation (PBM) may provide a viable therapeutic approach using red or near-infrared light to promote recovery after SCI by mitigating neuroinflammation and preventing neuronal apoptosis. Our current study aimed to optimize PBM dose regimens and develop and validate the efficacy of an invasive PBM delivery paradigm for SCI. Dose optimization studies were performed using a serum withdrawal model of injury in cultures of primary adult rat dorsal root ganglion neurons (DRGN). Implantable and transcutaneous PBM delivery protocols were developed and validated using cadaveric modeling. The efficacy of PBM in promoting recovery after SCI in vivo was studied in a dorsal column crush injury model of SCI in adult rats. Optimal neuroprotection in vitro was achieved between 4 and 22 mW/cm2. 11 mW/cm2 for 1 min per day (0.66 J/cm2) increased cell viability by 45% over 5 days (p <0.0001), increasing neurite outgrowth by 25% (p <0.01). A method for invasive application of PBM was developed using a diffusion-tipped optogenetics fiber optic. Delivery methods for PBM were developed and validated for both invasive (iPBM) and noninvasive (transcutaneous) (tcPBM) application. iPBM and tcPBM (24 mW/cm2 at spinal cord, 1 min per day (1.44 J/cm2) up to 7 days) increased activation of regeneration-associated protein at 3 days after SCI, increasing GAP43+ axons in DRGN from 18.0% (control) to 41.4% ± 10.5 (iPBM) and 45.8% ± 3.4 (tcPBM) (p <0.05). This corresponded to significant improvements at 6 weeks post-injury in functional locomotor and sensory function recovery (p <0.01), axonal regeneration (p <0.01), and reduced lesion size (p <0.01). Our results demonstrated that PBM achieved a significant therapeutic benefit after SCI, either using iPBM or tcPBM application and can potentially be developed for clinical use in SCI patients.
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Calcitonin gene related peptide monoclonal antibody treats headache in patients with active idiopathic intracranial hypertensionBackground: Headache is the dominant factor for quality of life related disability in idiopathic intracranial hypertension (IIH) and typically has migraine-like characteristics. There are currently no evidence-based therapeutics for headache in IIH, and consequently this is an important unmet clinical need. Case series: We report a series of seven patients in whom headaches were the presenting feature of IIH and the headaches had migraine-like characteristics, as is typical in many IIH patients. Papilloedema settled (ocular remission) but headaches continued. These headaches responded markedly to erenumab, a monoclonal antibody targeted against the calcitonin gene related peptide (CGRP) receptor. Of note, there was a recurrence of raised ICP, as evidenced by a return of the papilloedema, however the headaches did not recur whilst treated with erenumab. Conclusions: Those with prior IIH who have their headaches successfully treated with CGRP therapy, should remain under close ocular surveillance (particularly when weight gain is evident) as papilloedema can re-occur in the absence of headache. These cases may suggest that CGRP could be a mechanistic driver for headache in patients with active IIH.
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Using disease-modifying treatments in multiple sclerosis: Association of British Neurologists (ABN) 2024 guidance.The Association of British Neurologists last published guidelines on disease-modifying treatment (DMT) in multiple sclerosis (MS) in 2015. Since then, additional DMTs have been licensed and approved for prescribing within the National Health Service for relapsing-remitting MS, early primary progressive MS and active secondary progressive MS. This updated guidance provides a consensus-based approach to using DMTs. We provide recommendations for eligibility, starting, monitoring, switching and stopping of DMTs; pregnancy; equitable access to DMT; autologous haemopoietic stem-cell transplantation; and use of generics. We highlight best practice where it exists and discuss future priorities.
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Inflammatory Neuropathy Consortium base (INCbase): a protocol of a global prospective observational cohort study for the development of a prediction model for treatment response in chronic inflammatory demyelinating polyneuropathyBackground: INCbase is an international, multicenter prospective observational study using a customizable web-based modular registry to study the clinical, biological and electrophysiological variation and boundaries of chronic inflammatory demyelinating polyneuropathy (CIDP). The primary objective of INCbase is to develop and validate a clinical prediction model for treatment response. Methods: All patients meeting clinical criteria for CIDP can be included in INCbase. Collected data include demographics, clinical history, diagnostics and various domains of clinical outcomes. Data is collected at a minimum of every 6 months for two years, and more frequently at the discretion of the investigational site to allow for assessment of unexpected changes in treatment response or clinical status. Participants can be enrolled in various sub-studies designed to capture data relevant to specific groups of interest. Data is entered directly into the web-based data entry system by local investigators and/or participants. Collection and local storage of biomaterial is optional. To develop a clinical prediction model for treatment response, newly diagnosed patients with active disease warranting start of first-line treatment will be included. The study population will be split into a development and validation cohort. Univariate and multivariate logistic regression analysis will be used to identify and combine predictors at start of treatment for treatment response at six months. Model performance will be assessed through discrimination and calibration in an external validation cohort. The externally validated prediction model will be made available to researchers and clinicians on the INCbase website. Discussion: With this study, we aim to create a clinically relevant and implementable prediction model for treatment response to first line treatments in CIDP. INCbase enrollment started in April 2021, with 29 centers across 8 countries and 303 patients participating to date. This collaborative effort between academia, patient advocacy organizations and pharmaceutical industry will deepen our understanding of how to diagnose and treat CIDP.
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Brain network reorganisation and spatial lesion distribution in systemic lupus erythematosusObjective: This work investigates network organisation of brain structural connectivity in systemic lupus erythematosus (SLE) relative to healthy controls and its putative association with lesion distribution and disease indicators. Methods: White matter hyperintensity (WMH) segmentation and connectomics were performed in 47 patients with SLE and 47 healthy age-matched controls from structural and diffusion MRI data. Network nodes were divided into hierarchical tiers based on numbers of connections. Results were compared between patients and controls to assess for differences in brain network organisation. Voxel-based analyses of the spatial distribution of WMH in relation to network measures and SLE disease indicators were conducted. Results: Despite inter-individual differences in brain network organization observed across the study sample, the connectome networks of SLE patients had larger proportion of connections in the peripheral nodes. SLE patients had statistically larger numbers of links in their networks with generally larger fractional anisotropy weights (i.e. a measure of white matter integrity) and less tendency to aggregate than those of healthy controls. The voxels exhibiting connectomic differences were coincident with WMH clusters, particularly the left hemisphere's intersection between the anterior limb of the internal and external capsules. Moreover, these voxels also associated more strongly with disease indicators. Conclusion: Our results indicate network differences reflective of compensatory reorganization of the neural circuits, reflecting adaptive or extended neuroplasticity in SLE.
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Blood markers in remote ischaemic conditioning for acute ischaemic stroke: data from the REmote ischaemic conditioning after stroke trialBackground and purpose: Remote ischaemic per-conditioning (RIC) is neuroprotective in experimental ischaemic stroke. Several neurohumoral, vascular and inflammatory mediators are implicated. The effect of RIC on plasma biomarkers was assessed using clinical data from the REmote ischaemic Conditioning After Stroke Trial (RECAST-1). Methods: RECAST-1 was a pilot sham-controlled blinded trial in 26 patients with ischaemic stroke, randomized to receive four 5-min cycles of RIC within 24 h of ictus. Plasma taken pre-intervention, immediately post-intervention and on day 4 was analysed for nitric oxide (nitrate/nitrite) using chemiluminescence and all other biomarkers by multiplex analysis. Biomarkers were correlated with clinical outcome (day 90 National Institutes of Health Stroke Scale, modified Rankin Scale, Barthel index). Results: Remote ischaemic per-conditioning reduced serum amyloid protein (SAP) and tissue necrosis factor α (TNF-α) levels from pre- to post-intervention (n = 13, two-way ANOVA, p < 0.05). Overall (n = 26), increases in SAP pre- to post-intervention and pre-intervention to day 4 were moderately correlated with worse day 90 clinical outcomes. No consistent significant changes over time, or by treatment, or correlations with outcome were seen for other biomarkers. Conclusions: Remote ischaemic per-conditioning reduced SAP and TNF-α levels from pre- to post-intervention. Increases in plasma levels of SAP were associated with worse clinical outcomes after ischaemic stroke. Larger studies assessing biomarkers and the safety and efficacy of RIC in acute ischaemic stroke are warranted to further understand these relationships.
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A rare genetic cause of spastic paraparesisNo abstract available.
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Effect of proximal blood flow arrest during endovascular thrombectomy (ProFATE): a multicenter, blinded-end point, randomized clinical trialBackground: The effect of temporary blood flow arrest during endovascular thrombectomy for acute ischemic stroke is uncertain due to the lack of evidence from randomized controlled trials. We aimed to investigate whether temporary blood flow arrest during endovascular thrombectomy using a balloon guide catheter improves intracranial vessel recanalization compared with nonflow arrest. Methods: The ProFATE trial (Proximal Blood Flow Arrest During Endovascular Thrombectomy) was a multicenter, randomized, participant- and outcome-blinded trial at 4 thrombectomy centers in the United Kingdom. Adults with acute ischemic stroke due to anterior circulation large vessel occlusion were randomly assigned (1:1) by a central, Web-based program with a minimization algorithm to undergo thrombectomy with temporary proximal blood flow arrest or nonflow arrest during each attempt. The primary outcome was the proportion of participants achieving near-complete/complete vessel recanalization (expanded Thrombolysis in Cerebral Infarction score of 2c or 3) at the end of the thrombectomy procedure, adjudicated by a blinded independent imaging core laboratory. Analyses were performed on the intention-to-treat population, adjusted for age, IV thrombolysis, onset-to-randomization time, Alberta Stroke Program Early CT Score, occlusion site, randomization site, and National Institutes of Health Stroke Scale. Results: Between October 10, 2021, and June 27, 2023, we recruited 134 participants, of whom 131 participants (mean age, 75 years; 62 [47%] women and 69 [53%] men) were included in the final analysis. Sixty-six participants were allocated to the temporary blood flow arrest group and 65 to the nonflow arrest group. The proportion of participants with an expanded Thrombolysis in Cerebral Infarction 2c/3 score at the end of the endovascular procedure was 74.4% (49/66) in the flow arrest group and 70.8% (46/65) in the nonflow arrest group (adjusted odds ratio, 1.07 [95% CI, 0.45-2.55]; P=0.88). Among the prespecified secondary efficacy outcomes, a lower rate of emboli to a new vascular territory occurred in the blood flow arrest group compared with the nonflow arrest group (1.5% versus 12.3%; adjusted odds ratio, =0.04 [95% CI, 0.01-0.53]; P=0.014) and a higher rate of complete recanalization (expanded Thrombolysis in Cerebral Infarction score, 3) after the first attempt in the flow arrest group versus the nonflow arrest group (33.0% versus 15.3%; adjusted odds ratio, =3.80 [95% CI, 1.40-10.01]; P=0.007). No between-group differences were identified for the remaining procedural or clinical efficacy (modified Rankin Scale at 90 days) or safety outcomes (worsening of the stroke severity at 24 hours, adverse events, symptomatic intracranial hemorrhage, or mortality). Conclusions: Among patients presenting with anterior circulation large vessel occlusion acute ischemic stroke, temporary proximal blood flow arrest during endovascular thrombectomy, compared with nonflow arrest, did not significantly improve the near-complete/complete vessel recanalization (expanded Thrombolysis in Cerebral Infarction score, 2c-3) at the end of the procedure. Larger randomized controlled trials are warranted to confirm or refute a clinically significant treatment effect of temporary flow arrest on the functional outcome following endovascular thrombectomy. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05020795.
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Raman spectroscopy as a neuromonitoring tool in traumatic brain injury: a systematic review and clinical perspectivesTraumatic brain injury (TBI) is a significant global health problem, for which no disease-modifying therapeutics are currently available to improve survival and outcomes. Current neuromonitoring modalities are unable to reflect the complex and changing pathophysiological processes of the acute changes that occur after TBI. Raman spectroscopy (RS) is a powerful, label-free, optical tool which can provide detailed biochemical data in vivo. A systematic review of the literature is presented of available evidence for the use of RS in TBI. Seven research studies met the inclusion/exclusion criteria with all studies being performed in pre-clinical models. None of the studies reported the in vivo application of RS, with spectral acquisition performed ex vivo and one performed in vitro. Four further studies were included that related to the use of RS in analogous brain injury models, and a further five utilised RS in ex vivo biofluid studies for diagnosis or monitoring of TBI. RS is identified as a potential means to identify injury severity and metabolic dysfunction which may hold translational value. In relation to the available evidence, the translational potentials and barriers are discussed. This systematic review supports the further translational development of RS in TBI to fully ascertain its potential for enhancing patient care.
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CGRP therapy in primary care for migraine: prevention and acute medicationNo abstract available
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Assessing the landscape and charting paths : UK neurology trainees' opinions on neuroinflammation subspecialtyTherapeutics of neuroinflammatory disorders including multiple sclerosis is one of the fastest growing areas in neurology. However, pressures on higher specialty training in neurology together with an expanding curriculum have led to challenges in adequately preparing trainees for a subspecialist career. In this study we set out to understand current perceptions and barriers to training in neuroinflammatory disorders among neurology trainees in the UK. A structured questionnaire was used to assess trainees' perspectives on training opportunities and career aspirations. Findings reveal significant gaps in training, including insufficient training opportunities, lack of mentorship, and concerns about managing complex treatment regimes. We used these findings to develop structured action points with aim of improving training and retention in this subspecialty. These include early exposure to subspecialty experiences, enhanced mentorship, and equal access to training opportunities regardless of geographical location. Our findings underscore the need for further curriculum development in neurology training, potentially combining early support with dedicated fellowships later in training, in order to ensure sustainability of neuroinflammation as a subspecialty and to meet the growing demand for expertise in MS and related conditions.
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Antioxidant therapies in traumatic brain injuryDue to a multiplicity of causes provoking traumatic brain injury (TBI), TBI is a highly heterogeneous pathology, characterized by high mortality and disability rates. TBI is an acute neurodegenerative event, potentially and unpredictably evolving into sub-chronic and chronic neurodegenerative events, with transient or permanent neurologic, cognitive, and motor deficits, for which no valid standardized therapies are available. A vast body of literature demonstrates that TBI-induced oxidative/nitrosative stress is involved in the development of both acute and chronic neurodegenerative disorders. Cellular defenses against this phenomenon are largely dependent on low molecular weight antioxidants, most of which are consumed with diet or as nutraceutical supplements. A large number of studies have evaluated the efficacy of antioxidant administration to decrease TBI-associated damage in various animal TBI models and in a limited number of clinical trials. Points of weakness of preclinical studies are represented by the large variability in the TBI model adopted, in the antioxidant tested, in the timing, dosages, and routes of administration used, and in the variety of molecular and/or neurocognitive parameters evaluated. The analysis of the very few clinical studies does not allow strong conclusions to be drawn on the real effectiveness of antioxidant administration to TBI patients. Standardizing TBI models and different experimental conditions, as well as testing the efficacy of administration of a cocktail of antioxidants rather than only one, should be mandatory. According to some promising clinical results, it appears that sports-related concussion is probably the best type of TBI to test the benefits of antioxidant administration.
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Sumatriptan-naproxen sodium in migraine: A reviewBackground: Varied responses to acute migraine medications have been observed, with over one-third (34.5%) of patients reporting insufficient headache relief. Sumatriptan-naproxen sodium, a single, fixed-dose combination tablet comprising sumatriptan 85 mg and naproxen sodium 500 mg, was developed with the rationale of targeting multiple putative mechanisms involved in the pathogenesis of migraine to optimise acute migraine care. Methods: A narrative review of clinical trials investigating sumatriptan-naproxen sodium for both adults and adolescents was performed in March 2024. Results: Across a total of 14 clinical trials in nine publications, sumatriptan-naproxen sodium offered greater efficacy for 2-h pain freedom (14/14) and sustained pain-free response up to 24 h (13/14) compared with monotherapy and/or placebo for both adult and adolescent study participants with an acceptable and well-tolerated adverse effect profile. Clinical trial data also demonstrates the effectiveness of sumatriptan-naproxen sodium in participants with allodynia, probable migraine, menstrual-related migraine and those with poor responses to acute, non-specific, migraine medication. Conclusions: Multi-mechanistic therapeutic agents offer an opportunity to optimise acute medications by targeting multiple mediators involved in the pathogenesis of migraine. Sumatriptan-naproxen sodium resulted in greater initial and sustained pain freedom, compared with either sumatriptan, naproxen-sodium and/or placebo, for the treatment of single or multiple attacks of migraine across both adult and adolescent study populations.
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Clinical efficacy and safety of IV ferric carboxymaltose in restless legs syndrome: A meta-analysis of 537 patientsBackground: Recent research indicates that intravenous ferric carboxymaltose (IV FCM) presents a promising solution for Restless Legs Syndrome (RLS), distinguishing itself from other iron sources with minimal to no adverse effects. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety profile of administering IV FCM in patients with RLS, assuming that RLS and Iron deficiency anemia (IDA) are correlated. Methodology: This study was conducted according to the PRISMA guideline, with search conducted on PubMed, Google Scholar, and the Medline library. Data was extracted from each study regarding RLS and the effect of IV FCM on it, while analysis was conducted on Review Manager Software. Results: This meta-analysis comprises of 7 randomized controlled trials (RCTs). All 7 studies reported international RLS severity scale (IRLS) and the pooled analysis revealed a significant reduction in IRLS score favoring IV FCM [WMD: -6.03, 95 % CI (-10.11, -1.96), p = 0.004]. 3 out of 7 studies reported short form-36 health survey (SF-36) and the pooled analysis revealed that the total score of SF-36 significantly favors the group taking IV FCM [WMD: 7.44, 95%CI (1.67, 13.20) p = 0.01]. 4 out of 7 studies reported visual analogue scale (VAS) for RLS severity and pooled analysis revealed that IV FCM significantly decreased VAS) of RLS severity score as compared to the control [MD -19.21, 95%CI (-31.90, -6.52) p0.003]. Conclusion: The study findings support the efficacy of IVFCM in reducing the severity of RLS symptoms. Significant improvements in the IRLS scores were observed, alongside enhancements in overall quality of life measured by SF-36 scores.
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Unique diagnostic signatures of concussion in the saliva of male athletes: the Study of Concussion in Rugby Union through MicroRNAs (SCRUM)Objective: To investigate the role of salivary small non-coding RNAs (sncRNAs) in the diagnosis of sport-related concussion. Methods: Saliva was obtained from male professional players in the top two tiers of England's elite rugby union competition across two seasons (2017-2019). Samples were collected preseason from 1028 players, and during standardised head injury assessments (HIAs) at three time points (in-game, post-game, and 36-48 hours post-game) from 156 of these. Samples were also collected from controls (102 uninjured players and 66 players sustaining a musculoskeletal injury). Diagnostic sncRNAs were identified with next generation sequencing and validated using quantitative PCR in 702 samples. A predictive logistic regression model was built on 2017-2018 data (training dataset) and prospectively validated the following season (test dataset). Results: The HIA process confirmed concussion in 106 players (HIA+) and excluded this in 50 (HIA-). 32 sncRNAs were significantly differentially expressed across these two groups, with let-7f-5p showing the highest area under the curve (AUC) at 36-48 hours. Additionally, a combined panel of 14 sncRNAs (let-7a-5p, miR-143-3p, miR-103a-3p, miR-34b-3p, RNU6-7, RNU6-45, Snora57, snoU13.120, tRNA18Arg-CCT, U6-168, U6-428, U6-1249, Uco22cjg1,YRNA_255) could differentiate concussed subjects from all other groups, including players who were HIA- and controls, immediately after the game (AUC 0.91, 95% CI 0.81 to 1) and 36-48 hours later (AUC 0.94, 95% CI 0.86 to 1). When prospectively tested, the panel confirmed high predictive accuracy (AUC 0.96, 95% CI 0.92 to 1 post-game and AUC 0.93, 95% CI 0.86 to 1 at 36-48 hours). Conclusions: SCRUM, a large prospective observational study of non-invasive concussion biomarkers, has identified unique signatures of concussion in saliva of male athletes diagnosed with concussion.
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Medication-overuse headache: update on managementLong-term frequent use of acute pain medication for the treatment of headaches has paradoxically been shown to increase the frequency of headaches. So-called medication-overuse headache (MOH) is particularly problematic in patients with migraine who overuse triptans and opioids. Prevention through education remains the most important management strategy. Once established, MOH can be difficult to treat. Although complete or near-complete withdrawal of acute pain medication for 8-12 weeks has been shown to benefit most patients, this can be hard to achieve. The use of OnabotulinumtoxinA and drugs that target the calcitonin gene-related peptide system for the prevention of migraines have been shown to benefit patients with MOH. Furthermore, the use of novel acute pain medication for migraines, including Gepants and Ditans, which do not cause MOH, are likely to improve patient outcomes. In this review article we examine the following: the burden of MOH; who develops MOH; the pathophysiological mechanisms; and the treatment strategies.
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Patient-completed online "follow-up form" to assess continuation of anti-CGRP(r) antibody therapy in patients with chronic migraine: a pilot studyBackground: The introduction of new drugs that target the Calcitonin Gene-Related Peptide (CGRP) system has provided significant hope for patients with otherwise treatment-resistant migraine, but also resulted in significant capacity issues at the point of delivery, as patients require follow-up at certain timepoints. Aim: Pilot a patient-completed "follow-up form" (FuF) to replace direct patient contact at the time of 1-year treatment review in patients receiving anti-CGRP (receptor (r)) antibody therapy for chronic migraine. Methods: Patients with chronic migraine already receiving anti-CGRP(r) antibody therapy and due for 1-year review were contacted by telephone and recruited into the study. Patients completed a simple online form, which mirrored questions asked at 1-year follow-up, and a patient satisfaction survey. Results: Thirty-nine (78 %) of 50 patients completed the FuF, which resulted in further telephone contact in 3 (8 %) patients. Over 90 % strongly agreed that the FuF was easy to understand and complete. 80 % strongly agreed that they felt confident in decision making regarding continuation or cessation of anti-CGRP(r) antibody therapy. Overall, 88 % rated their experience of the online form as "Excellent" and 12 % as "Good". Conclusions: Within our headache service, we have demonstrated that an appropriately designed online patient-completed form has the potential to replace direct patient contact at 1-year review in patients already receiving anti-CGRP(r) antibody therapy for chronic migraine.