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Publication Hereditary geniospasm (chin tremor)(BMJ, 2025-04-24) Nasim, Saneeya; Davies, Sarah; Wakerley, Benjamin R; University Hospitals Birmingham NHS Foundation Trust; University of Birmingham; Neurology; Medical and Dental; Wakerley, BenjaminNo abstract availablePublication Golden Hour for Stroke (GHoSt) – a prospective observational study of biomarkers in acute stroke(University Hospitals Birmingham NHS Foundation Trust, 2024-09-17) Smith, Hazel; Luxmore-Brown, Scott; Miller, Josh; Momin, Sheikh; University Hospitals Birmingham NHS Foundation Trust; Research and Development; Neurosurgery; Allied Health Professional; Medical and Dental; Smith, Hazel; Luxmore-Brown, Scott; Momin, SheikhIntroduction Golden Hour study started in 2014 identified early biomarkers in blood and saliva specific to concussion. RECOS and SCRUM studies used these in athletes as part of a suite of tests designed to diagnose concussion pitch-side. We adapted the Golden Hour study to screen for biomarkers in patients with suspected stroke to identify those who have had a stroke versus those who have mimics, hence the Golden Hour for Stroke (GHoSt) study. Early recognition of stroke versus mimic could support decision-making ensuring patients are taken to the correct place for treatment more quickly, improving long- and short-term outcomes. Methods A Stroke Association Research Grant will allow training of WMAS paramedics in sample collection from 200 patients with suspected stroke. Samples will be brought with patients to the Queen Elizabeth Hospital, Birmingham (part of UHB) for analysis by University of Birmingham (UoB) scientists. Data will be collected and patients consented by Research Nurses and diagnosis of stroke or mimic will be carried out by a Consultant Neurologist. Data analysis will be provided by a UoB Statistician and study oversight by experts. Only by working in this collaborative way can we achieve our goal. Sampling will be at various intervals between time of 999 call and 1-year. A predefined panel of biomarkers of acute brain injury will be analysed, as well as an exploratory analysis of significantly expressed biomarkers. Outcomes of the study are effectiveness of biomarkers in differentiating between stroke and stroke mimic up to 24 hours from symptom onset and the modified Rankin Scale (mRS) at 3 months. Results GHoSt is unique in two perspectives: 1. Facilitation is only possible because of past experience working as a multi-disciplinary team on Golden Hour and other studies. 2. Paramedics do not routinely take blood or saliva samples so this trial will provide them with a new skill. Conclusion Our future aim is to use biomarkers to differentiate between haemorrhagic vs ischaemic stroke. This will support decision-making at point of 999 call as well as allow much faster treatment of stroke than is currently possible.Publication Evolving immunologic perspectives in chronic inflammatory demyelinating polyneuropathy.(Dove Medical Press, 2020-09-16) Rajabally, Yusuf A; Attarian, Shahram; Delmont, Emilien; Neurology; Medical and Dental; Rajabally, YusufChronic inflammatory demyelinating polyneuropathy (CIDP) is the commonest chronic idiopathic dysimmune neuropathy. Pathophysiologic processes involve both cellular and humoral immunity. There are various known forms of CIDP, likely caused by varying mechanisms. CIDP in its different forms is a treatable disorder in the majority of patients. The diagnosis of CIDP is clinical, supported routinely by electrophysiology. Cerebrospinal fluid analysis may be helpful. Routine immunology currently rarely adds to the diagnostic process but may contribute to the identification of an associated monoclonal gammopathy with or without hematologic malignancy and the consideration of alternative diagnoses, such as POEMS syndrome, anti-myelin associated glycoprotein (MAG) neuropathy or chronic ataxic neuropathy, with ophthalmoplegia, M-protein, cold aglutinins and disialosyl antibodies (CANOMAD). The search for antibodies specific to CIDP has been unsuccessful for many years. Recently, antibodies to paranodal proteins have been identified in a minority of patients with severe CIDP phenotypes, often unresponsive to first-line therapies. In conjunction with reports of high rates of antibody responses to neural structures in CIDP, this entertains the hope that more discoveries are to come. Although still arguably for only a small minority of patients, in view of current knowledge, such progress will enable earlier accurate diagnosis with direct management implications but only if the important, unfortunately and infrequently discussed issues of immunologic technique, test reliability and reproducibility are adequately tackled.Publication Erenumab for headaches in idiopathic intracranial hypertension: A prospective open-label evaluation.(Wiley, 2020-12-14) Yiangou, Andreas; Mitchell, James L; Fisher, Claire; Edwards, Julie; Vijay, Vivek; Alimajstorovic, Zerin; Grech, Olivia; Lavery, Gareth G; Mollan, Susan P; Sinclair, Alexandra J; Neurology; Doctors; Medical and Dental; Yiangou, Andreas; Mitchell, James L; Sinclair, Alexandra JObjective: To determine the effectiveness of erenumab in treating headaches in idiopathic intracranial hypertension (IIH) in whom papilledema had resolved. Background: Disability in IIH is predominantly driven by debilitating headaches with no evidence for the use of preventative therapies. Headache therapy in IIH is an urgent unmet need. Methods: A prospective, open-label study in the United Kingdom was conducted. Adult females with confirmed diagnosis of IIH now in ocular remission (papilledema resolved) with chronic headaches (≥15 days a month) and failure of ≥3 preventative medications received erenumab 4-weekly (assessments were 3-monthly). The primary end point was change in monthly moderate/severe headache days (MmsHD) from baseline (30-day pretreatment period) compared to 12 months. Results: Fifty-five patients, mean (SD) age 35.3 (9) years and mean duration of headaches 10.4 (8.4) years with 3.7 (0.9) preventative treatment failures, were enrolled. Mean baseline MmsHD was 16.1 (4.7) and total monthly headache days (MHD) was (29) 2.3. MmsHD reduced substantially at 12 months by mean (SD) [95% CI] 10.8 (4.0) [9.5, 11.9], p < 0.001 and MHD reduced by 13.0 (9.5) [10.2, 15.7], p < 0.001. Crystal clear days (days without any head pain) increased by 13.1 (9.5) [9.6, 15.3], p < 0.001, headache severity (scale 0-10) fell by 1.3 (1.7) [0.9, 1.9], p < 0.001, and monthly analgesic days reduced by 4.3 (9.2) [1.6, 6.9], p = 0.002. All these measures had improved significantly by 3 months, with a consistent significant response to 12 months. Headache impact test-6 score and quality of life Short Form-36 Health Survey significantly improved at 12 months. Sensitivity analysis revealed similar results for patients with and without a prior migraine diagnosis (28/55 (52%) patients) or those with or without medication overuse (27/55 (48%) patients). Conclusions: This study provides evidence for the effectiveness of erenumab to treat headaches in IIH patients with resolution of papilledema. It provides mechanistic insights suggesting that calcitonin gene-related peptide is likely a modulator driving headache and a useful therapeutic target.Publication Electrophysiology in CIDP: should we use it beyond diagnosis?(Elsevier, 2020-10-29) Rajabally, Yusuf A; Goedee, H Stephan; Neurology; Medical and Dental; Rajabally, YusufNo abstract availablePublication Emerging themes in idiopathic intracranial hypertension.(Springer-Verlag, 2020-07-22) Grech, Olivia; Mollan, Susan P; Wakerley, Benjamin R; Alimajstorovic, Zerin; Lavery, Gareth G; Sinclair, Alexandra J; Doctors; Medical and Dental; Sinclair, AlexandraPurpose: Idiopathic intracranial hypertension (IIH) is a rare disorder characterised by raised intracranial pressure. The underlying pathophysiology is mostly unknown and effective treatment is an unmet clinical need in this disease. This review evaluates key emerging themes regarding disease characteristics, mechanisms contributing to raised intracranial pressure and advances in potential therapeutic targets. Findings: IIH is becoming more common, with the incidence rising in parallel with the global obesity epidemic. Current medical management remains centred around weight management, which is challenging. Metabolic investigations of patients have identified specific androgen profiles in cerebrospinal fluid (CSF), which suggest an endocrine dysfunction impacting CSF secretion in IIH. Glucagon-like peptide-1 (GLP-1) and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) have been found to play a role in CSF dynamics in IIH and have formed the basis of the first clinical trials looking at new treatments. Conclusions: Identification of novel molecular targets thought to underlie IIH pathology is now being translated to clinical trials.Publication Absence of monitoring in withdrawal of clinically-assisted nutrition and hydration (CANH) and other treatments: a cause for concern?(Elsevier, 2021-05) Gray, Alice; Pickering, Mark; Sturman, Stephen; Neurology; Medical and Dental; Sturman, StephenSince 2018, there has been no requirement to bring decisions about the withdrawal of clinically-assisted nutrition and hydration (CANH) in patients with persistent disorders of consciousness before the courts, providing that the requirements of the Mental Capacity Act 2005 (MCA) are fulfilled. Subsequent British Medical Association and Royal College of Physicians guidance on CANH withdrawal recommended standards of record keeping and internal and external audit to ensure local decision making was compliant with the MCA to safeguard patients. The scope of the guidance also included patients with stroke and neurodegenerative disorders.Freedom of Information requests made 2 years after the introduction of this guidance have shown that none of the NHS trusts or clinical commissioning groups who responded were undertaking any systematic monitoring of these decisions. Neither is the Care Quality Commission reviewing these decisions, as there is 'no statutory requirement' to do so. It appears there is a lack of organised scrutiny of these highly complex life-ending treatment decisions. This omission must surely be a cause for concern.Publication Ischemic heart disease among South Asians with ischaemic stroke in three countries across two continents : the BRAINS study(Elsevier, 2025-02-19) Ken-Dror, Gie; Sureshkumar, Prianka; Han, Thang S; Sharma, Sapna D; Sylaja, Padmavathy N; Khan, Fahmi Yousef; Prasad, Kameshwar; Sharma, Pankaj; University of London; Sree Chitra Tirunal Institute for Medical Sciences and Technology; Hamad Medical Corporation; Sandwell and West Birmingham NHS Trust; et al.; Stroke; Nursing; Ispoglou, Sissi; Medical and Dental; Ispoglou, Sissi; Carr, PeterBackground: Ischaemic heart disease (IHD) and cardiometabolic risk factors have been extensively investigated in those of European descent, yet they are more common among South Asians who make up around 20% of the world's population. We explored the differences in IHD and cumulative metabolic profile in South Asians with stroke living in the UK, India and Qatar, compared with white British stroke patients. Methods: The study included first-ever ischemic stroke white British patients and South Asians living in UK, India and Qatar from the ongoing large Bio-Repository of DNA in Stroke (BRAINS) international hospital-based stroke study. Results: We analysed 4359 patients of which 1575 were white British (WB) UK residents, 1135 British South Asians (BSA), 1084 South Asians in India (ISA), and 565 South Asians in Qatar (QSA). Stroke patients from BSA and ISA background had a 9.5% (95%CI: 6.2-12.9, P<0.001) and 15.8% (95%CI: 13.1-28.9, P<0.001) higher prevalence of IHD respectively, compared to WB patients. Adjusting for traditional stroke risk factors, BSA patients continued to display an increased association of IHD compared to WB patients: OR=1.59 (95%CI: 1.25-2.02, P<0.001). Among South Asian ethnicity, compared to ISA, BSA had an almost twice the association of IHD: OR=1.83 (95%CI: 1.37-2.45, P<0.001). The OR for the presence of 2, or ≥3 cumulative cardiometabolic risk factors was 2.55 (95%CI: 2.02-3.23, P<0.001), and 3.86 (95%CI: 3.02-4.95, P<0.001) for South Asians (ISA, BSA, QSA) compared to WB patients, respectively. Conclusion: South Asian ischaemic stroke immigrants have a higher prevalence of IHD as well as more cumulative cardiometabolic risk factors compared to those who remain on the subcontinent. Countries with large immigrant South Asian populations should focus public health campaigns to mitigate their high cardiometabolic risk profiles.Publication Autoantibodies in the diagnostic work-up of neuropathy: clinically useful or purely academic?(MA Healthcare, 2020-07-20) Sahi, Nitin; Ghasemi, Majid; Rajabally, Yusuf A; Neurology; Medical and Dental; Rajabally, YusufThe search for autoantibodies in patients with acute and chronic neuropathies has become widespread in neurological practice. These tests are more routinely available and therefore are more commonly requested in larger hospitals with neuroscience centres, although they are now also regularly requested from district general hospital settings, including by non-neurologists. However, the clinical value of these frequently expensive tests is often unclear and their impact on management not always obviously beneficial. This article reviews the main immunological tests used to search for specific autoantibodies in the setting of neuropathy and discusses their potential diagnostic importance, together with the eventual therapeutic implications of results obtained.Publication 11β-Hydroxysteroid dehydrogenase type 1 inhibition in idiopathic intracranial hypertension: a double-blind randomized controlled trial.(Oxford University Press, 2020-01-10) Markey, Keira; Mitchell, James; Botfield, Hannah; Ottridge, Ryan S; Matthews, Tim; Krishnan, Anita; Woolley, Rebecca; Westgate, Connar; Yiangou, Andreas; Alimajstorovic, Zerin; Shah, Pushkar; Rick, Caroline; Ives, Natalie; Taylor, Angela E; Gilligan, Lorna C; Jenkinson, Carl; Arlt, Wiebke; Scotton, William; Fairclough, Rebecca J; Singhal, Rishi; Stewart, Paul M; Tomlinson, Jeremy W; Lavery, Gareth G; Mollan, Susan P; Sinclair, Alexandra J; Neurology; Doctors; Surgery; Medical and Dental; Mitchell, James; Yiangou, Andreas; Scotton, William; Sinclair, Alexandra J; Singhal, RishiTreatment options for idiopathic intracranial hypertension are limited. The enzyme 11β-hydroxysteroid dehydrogenase type 1 has been implicated in regulating cerebrospinal fluid secretion, and its activity is associated with alterations in intracranial pressure in idiopathic intracranial hypertension. We assessed therapeutic efficacy, safety and tolerability and investigated indicators of in vivo efficacy of the 11β-hydroxysteroid dehydrogenase type 1 inhibitor AZD4017 compared with placebo in idiopathic intracranial hypertension. A multicenter, UK, 16-week phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017 or placebo was conducted. Women aged 18-55 years with active idiopathic intracranial hypertension (>25 cmH2O lumbar puncture opening pressure and active papilledema) were included. Participants received 400 mg of oral AZD4017 twice daily compared with matching placebo over 12 weeks. The outcome measures were initial efficacy, safety and tolerability. The primary clinical outcome was lumbar puncture opening pressure at 12 weeks analysed by intention-to-treat. Secondary clinical outcomes were symptoms, visual function, papilledema, headache and anthropometric measures. In vivo efficacy was evaluated in the central nervous system and systemically. A total of 31 subjects [mean age 31.2 (SD = 6.9) years and body mass index 39.2 (SD = 12.6) kg/m2] were randomized to AZD4017 (n = 17) or placebo (n = 14). At 12 weeks, lumbar puncture pressure was lower in the AZD4017 group (29.7 cmH2O) compared with placebo (31.3 cmH2O), but the difference between groups was not statistically significant (mean difference: -2.8, 95% confidence interval: -7.1 to 1.5; P = 0.2). An exploratory analysis assessing mean change in lumbar puncture pressure within each group found a significant decrease in the AZD4017 group [mean change: -4.3 cmH2O (SD = 5.7); P = 0.009] but not in the placebo group [mean change: -0.3 cmH2O (SD = 5.9); P = 0.8]. AZD4017 was safe, with no withdrawals related to adverse effects. Nine transient drug-related adverse events were reported. One serious adverse event occurred in the placebo group (deterioration requiring shunt surgery). In vivo biomarkers of 11β-hydroxysteroid dehydrogenase type 1 activity (urinary glucocorticoid metabolites, hepatic prednisolone generation, serum and cerebrospinal fluid cortisol:cortisone ratios) demonstrated significant enzyme inhibition with the reduction in serum cortisol:cortisone ratio correlating significantly with reduction in lumbar puncture pressure (P = 0.005, R = 0.70). This is the first phase II randomized controlled trial in idiopathic intracranial hypertension evaluating a novel therapeutic target. AZD4017 was safe and well tolerated and inhibited 11β-hydroxysteroid dehydrogenase type 1 activity in vivo. Reduction in serum cortisol:cortisone correlated with decreased intracranial pressure. Possible clinical benefits were noted in this small cohort. A longer, larger study would now be of interest.Publication 11βHSD1 inhibition with AZD4017 improves lipid profiles and lean muscle mass in idiopathic intracranial hypertension.(Oxford University Press, 2021-01-01) Hardy, Rowan S; Botfield, Hannah; Markey, Keira; Mitchell, James L; Alimajstorovic, Zerin; Westgate, Connar S J; Sagmeister, Michael; Fairclough, Rebecca J; Ottridge, Ryan S; Yiangou, Andreas; Storbeck, Karl-Heinz H; Taylor, Angela E; Gilligan, Lorna C; Arlt, Wiebke; Stewart, Paul M; Tomlinson, Jeremy W; Mollan, Susan P; Lavery, Gareth G; Sinclair, Alexandra J; Neurology; Doctors; Medical and Dental; Mitchell, James L; Yiangou, Andreas; Sinclair, Alexandra JBackground: The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) determines prereceptor metabolism and activation of glucocorticoids within peripheral tissues. Its dysregulation has been implicated in a wide array of metabolic diseases, leading to the development of selective 11β-HSD1 inhibitors. We examined the impact of the reversible competitive 11β-HSD1 inhibitor, AZD4017, on the metabolic profile in an overweight female cohort with idiopathic intracranial hypertension (IIH). Methods: We conducted a UK multicenter phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017. Serum markers of glucose homeostasis, lipid metabolism, renal and hepatic function, inflammation and androgen profiles were determined and examined in relation to changes in fat and lean mass by dual-energy X-ray absorptiometry. Results: Patients receiving AZD4017 showed significant improvements in lipid profiles (decreased cholesterol, increased high-density lipoprotein [HDL] and cholesterol/HDL ratio), markers of hepatic function (decreased alkaline phosphatase and gamma-glutamyl transferase), and increased lean muscle mass (1.8%, P < .001). No changes in body mass index, fat mass, and markers of glucose metabolism or inflammation were observed. Patients receiving AZD4017 demonstrated increased levels of circulating androgens, positively correlated with changes in total lean muscle mass. Conclusions: These beneficial metabolic changes represent a reduction in risk factors associated with raised intracranial pressure and represent further beneficial therapeutic outcomes of 11β-HSD1 inhibition by AZD4017 in this overweight IIH cohort. In particular, beneficial changes in lean muscle mass associated with AZD4017 may reflect new applications for this nature of inhibitor in the management of conditions such as sarcopenia. Trial registration: ClinicalTrials.gov NCT02017444.Publication The effects of adrenal insufficiency and its treatment on cognition in an athlete with post-concussion syndrome(Routledge, 2024-12-17) Wilson, Holly; Paton, Emily; Hacker, David; Stevens, Andrew; Belli, Antonio; Yakoub, Kamal; Jones, Christopher A; Hawkins, Andrew; Neurosurgery; Neuropsychology; Additional Clinical Services; Additional Professional Scientific and Technical Field; Admin and Clerical; Paton, Emily; Belli, Antonio; Hawkins, AndrewPost-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.Publication Implantable and transcutaneous photobiomodulation promote neuroregeneration and recovery of lost function after spinal cord injury.(John Wiley & Sons Inc., 2024-04-25) Stevens, Andrew R; Hadis, Mohammed; Phillips, Alice; Thareja, Abhinav; Milward, Michael; Belli, Antonio; Palin, William; Davies, David J; Ahmed, Zubair; Neurosurgery; Admin and Clerical; Davies, DavidSpinal 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.Publication Calcitonin gene related peptide monoclonal antibody treats headache in patients with active idiopathic intracranial hypertension(BioMed Central, 2020-09-25) Yiangou, Andreas; Mitchell, James L; Vijay, Vivek; Grech, Olivia; Bilton, Edward; Lavery, Gareth G; Fisher, Claire; Edwards, Julie; Mollan, Susan P; Sinclair, Alexandra J; University of Birmingham; Birmingham Health Partners; University Hospitals Birmingham NHS Foundation Trust; Neurology; Ophthalmology; Medical and Dental; Yiangou, Andreas; Mitchell, James; Mollan, Susan; Sinclair, AlexandraBackground: 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.Publication Burden of illness in chronic inflammatory demyelinating polyneuropathy: some facts and solutions(Springer Verlag, 2020-07-27) Rajabally, Yusuf A; University Hospitals Birmingham NHS Foundation Trust; Aston University; Neurology; Medical and Dental; Rajabally, YusufNo abstract availablePublication Using disease-modifying treatments in multiple sclerosis: Association of British Neurologists (ABN) 2024 guidance.(BMJ Pub, 2024-11-11) Rashid, Waqar; Ciccarelli, Olga; Leary, Siobhan M; Arun, Tarunya; Doshi, Anisha; Evangelou, Nikos; Ford, Helen L; Hobart, Jeremy; Jacob, Saiju; Muraro, Paolo Antonio; Murray, Katy; Palace, Jacqueline; Dobson, Ruth; Neurology; Medical and Dental; Jacob, SaijuThe 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.Publication 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 polyneuropathy(BioMed Central, 2024-10-25) Michael, Milou R; Wieske, Luuk; Allen, Jeffrey A; Lunn, Michael P; Doppler, Kathrin; Tan, Cheng-Yin; Koike, Haruki; Markvardsen, Lars K; Kapoor, Mahima; Hsieh, Sung-Tsang; Nobile-Orazio, Eduardo; Jacobs, Bart C; Rajabally, Yusuf A; Basta, Ivana; Ripellino, Paolo; Querol, Luis; Eftimov, Filip; Neurology; Medical and Dental; Rajabally, Yusuf ABackground: 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.Publication Brain network reorganisation and spatial lesion distribution in systemic lupus erythematosus(Sage, 2020-12-13) Valdés Hernández, Maria Del C; Smith, Keith; Bastin, Mark E; Nicole Amft, E; Ralston, Stuart H; Wardlaw, Joanna M; Wiseman, Stewart J; University of Edinburgh; Health Data Research UK; University Hospitals Birmingham NHS Foundation Trust; Rheumatology; Medical and Dental; Amft, NicoleObjective: 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.Publication Blood markers in remote ischaemic conditioning for acute ischaemic stroke: data from the REmote ischaemic conditioning after stroke trial(Wiley, 2020-11-20) Appleton, Jason P; O'Sullivan, Saoirse E; Hedstrom, Amanda; May, Jane A; Donnelly, Richard; Sprigg, Nikola; Bath, Philip M; England, Timothy J; University of Nottingham; University Hospitals Birmingham NHS Foundation Trust; Nottingham University Hospitals NHS Trust; University Hospitals of Derby and Burton NHS Foundation TrustBackground 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.Publication A rare genetic cause of spastic paraparesis(Lippincott Williams & Wilkins, 2024-12-02) Bhattacharjee, Shakya; Siripurapu, Rekha; Swale, Andrew; Crow, Yanick J; Kobylecki, Christopher; Neurology; Medical and Dental; Bhattacharjee, Shakya; J Crow, Yanick; Kobylecki, ChristopherNo abstract available.