James Mitchell

• Doctor of Philosophy
• Lecturer Neurology at University of Birmingham

Introduction Mild traumatic brain injury (TBI) affects a significant number of military personnel, primarily because of physical impact, vehicle incidents, and blast exposure. Post-traumatic headache (PTH) is the most common symptom reported following mild TBI and can persist for several years. However, the current International Classification of H...

Mild traumatic brain injury (mTBI) is common with many patients suffering disabling long-term sequelae, with visual symptoms frequently reported. There are no objective biomarkers of mTBI that are routinely used in clinical practice. Optical coherence tomography (OCT) has been used in mTBI research, as it enables visualisation of the neuroretina, a...

Background Cognitive function can be affected in conditions with raised intracranial pressure (ICP) such as idiopathic intracranial hypertension (IIH). Drugs used off label to treat raised ICP also have cognitive side effects, underscoring the unmet need for effective therapeutics which reduce ICP without worsening cognition. The Glucagon Like Pept...

Idiopathic intracranial hypertension (IIH) is a disease characterised by elevated intracranial pressure (ICP). The impact of straining and exercise on ICP regulation is poorly understood yet clinically relevant to IIH patient care. We sought to investigate the impact of Valsalva manoeuvres (VMs) and exercise on ICP and cerebrovascular haemodynamics...

Idiopathic intracranial hypertension, a disease classically occurring in women with obesity, is characterized by raised intracranial pressure. Weight loss leads to the reduction in intracranial pressure. Additionally, pharmacological glucagon-like peptide-1 agonism reduces cerebrospinal fluid secretion and intracranial pressure. The potential mecha...

Background The medium-long impact of coronavirus disease 2019 (COVID-19) on active populations is yet to be fully understood, with potential individual and operational impact on military service personnel (SP). The M-COVID study was established to investigate cardiopulmonary, functional, cognitive, and mental health post-COVID-19 SP outcomes, acros...

Purpose: This study was designed to determine if point analysis of the Humphrey visual field (HVF) is an effective outcome measure for people with idiopathic intracranial hypertension (IIH) compared with mean deviation (MD). Methods: Using the IIH Weight Trial data, we performed a pointwise analysis of the numerical retinal sensitivity. We then...

Therapeutics to reduce intracranial pressure are an unmet need. Preclinical data have demonstrated a novel strategy to lower intracranial pressure using glucagon-like peptide-1 (GLP-1) receptor signalling. Here, we translate these findings into patients by conducting a randomized, placebo-controlled, double-blind trial to assess the effect of exena...

Background The COVID-19 pandemic has led to significant morbidity and mortality, with the former impacting and limiting individuals requiring high physical fitness, including sportspeople and emergency services. Methods Observational cohort study of 4 groups: hospitalised, community illness with on-going symptoms (community-symptomatic), community...

Background: Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure occurring predominantly in women with obesity. The pathogenesis is not understood. We have applied untargeted metabolomic analysis using ultrahigh-performance liquid chromatography-mass spectrometry to characterize the cerebrospinal fluid (CSF...

Background Multiple lumbar punctures have historically been a strategy to relieve headaches associated with idiopathic intracranial hypertension despite limited clinical evidence of long-term efficacy. Lumbar puncture is typically a straightforward procedure with minimal complications reported, however, serious complications can occur. Lumbar-punct...

Objectives Intracranial pressure (ICP) has been thought to vary diurnally. This study evaluates diurnal ICP measurements and quantifies changes in ICP occurring with changes in body posture in active idiopathic intracranial hypertension (IIH). Methods This prospective observational study utilized telemetric ICP monitoring in people with active IIH...

Background and Objective We evaluated the metabolomic profile in CSF, serum and urine of participants with idiopathic intracranial hypertension (IIH) compared to controls and measured changes in metabolism associated with clinical markers of disease activity and treatment. Methods A case-control study compared women aged 18-55 years with active II...

Therapeutics to reduce intracranial pressure are an unmet need. Pre-clinical data has demonstrated a novel strategy to lower intracranial pressure using glucagon-like peptide-1 receptor signaling. Here, we translate these findings into patients by conducting a randomized, placebo controlled, double-blind trial to assess the effect of exenatide, a g...

Background Mild traumatic brain injury (mTBI) is common accounting for 1.4 million hospital visits annually in the UK. Although classified as mild it leads to disproportionate impact on future health. Many suffer long-term disability driven by post-traumatic headache, mood and visual disturbances, vestibular dys- function, post-traumatic stress dis...

Obesity is a risk factor for idiopathic intracranial hypertension (IIH) and obstructive sleep apnoea (OSA). We aimed to determine the prevalence of OSA in IIH and evaluate the diagnostic performance of OSA screening tools in IIH. Additionally, we evaluated the relationship between weight loss, OSA and IIH over 12-months. A sub-study of a multi-cent...

Lumbar puncture (LP) is a common diagnostic procedure in clinical neurology. Iatrogenic spinal haema- tomas can be a complication of LPs and range from mild and self-resolving to very severe or even fatal. We describe a case report and review current literature on post-LPs spinal haematomas. A 28-year-old Lady with a background of post-meningitic h...

Background and objectives: The idiopathic intracranial hypertension randomized controlled weight trial (IIH:WT) established that weight loss through bariatric surgery significantly reduced intracranial pressure compared to a community weight management intervention. This sub-study aimed to evaluate the amount of weight loss required to reduce intr...

Introduction There have been more than 425 million COVID-19 infections worldwide. Post-COVID illness has become a common, disabling complication of this infection. Therefore, it presents a significant challenge to global public health and economic activity. Methods Comprehensive clinical assessment (symptoms, WHO performance status, cognitive test...

Purpose Using the Idiopathic Intracranial Hypertension Weight Trial (IIH:WT) data, this study aimed to determine if point analysis of the Humphrey visual field (HVF) could be more informative than the perimetric mean deviation (PMD) as an IIH trial outcome measure. Methods IIH:WT was a randomized controlled trial that recruited 66 people with acti...

Aim To determine whether Optical Coherence Tomography (OCT) of the optic nerve head in papil- loedema could act as a surrogate measure of intracranial pressure (ICP). Methods This is a longitudinal cohort study using data collected from three randomised controlled trials, between from April 1st, 2014 to August, 1st 2019. OCT imaging and automated...

Background Pre-clinical data demonstrates the ability of Exenatide, a GLP-1R agonist, to reduce CSF secretion and ICP.1 Existing GLP-1R agonists are widely used to treat obesity and diabetes (but do not cause hypoglycaemia). Methods Randomised, placebo controlled, double-blind trial of Exenatide in women with active IIH. Participants were randomis...

Headache therapy is an unmet need in idiopathic intracranial hypertension (IIH). This was a prospective, real world, open-label cohort study over 9 months in the UK. Adult females with confirmed diagnosis of IIH now in ocular remission with chronic migraine (CM)-like headaches and failure of ≥3 preventative medications received Erenumab 70mg monthl...

Objective Headache is the predominant disabler in idiopathic intracranial hypertension (IIH). The aim was to characterise headache and investigate the association with intracranial pressure (ICP). Methods IIH:WT was a randomised controlled parallel group multicentre trial investigating weight manage- ment methods in IIH. Participants with active I...

Background 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 p...

Objective The IIH weight trial (IIH: WT) aimed to compare the efficacy of bariatric surgery with a community weight management intervention (CWI) in active IIH. Methods This was a five-year randomized control trial which enrolled participants between March 1, 2014 and May 25, 2017 at five NHS hospitals in the United Kingdom. Participants with acti...

Idiopathic intracranial hypertension (IIH) is an increasingly prevalent disease, characterised by raised intracranial pressure (ICP). Cognitive impairments have been reported in IIH, however evidence support- ing these deficits are scarce and contributing factors have not been defined. Using a bespoke battery of cognitive tests, we identified multi...

Background The amount of weight loss required in idiopathic intracranial hypertension to reduce intrac- ranial pressure (ICP) has not been established. Methods Using the IIH:weight trial data from 66 active patients randomised to bariatric surgery or community weight management intervention (CWI) (1:1) a linear hierarchical regression model was us...

Objectives: Intracranial pressure (ICP) has been thought to vary diurnally. This study evaluates diurnal ICP measurements and quantifies changes in ICP occurring with changes in body posture in active idiopathic intracranial hypertension (IIH). Methods: This prospective observational study utilized telemetric ICP monitoring in people with active II...

Context Idiopathic intracranial hypertension (IIH) is a disease of raised intracranial pressure (ICP) of unknown aetiology. Reductions in glucocorticoid metabolism are associated with improvements in IIH disease activity. The basal IIH glucocorticoid metabolism yet to be assessed. Objective To determine the basal glucocorticoid phenotype in IIH and...

Objective Obesity is a risk factor for idiopathic intracranial hypertension (IIH) and obstructive sleep apnoea (OSA). We aimed to determine the prevalence of OSA in IIH and evaluate the diagnostic performance of OSA screening tools in IIH. Additionally, we evaluated the relationship between weight loss, OSA and IIH over 12 months. Methods A sub-st...

Objectives: To investigate cardiopulmonary, functional, cognitive, and mental health post-COVID-19 outcomes in a young, physically active working-age population, across the spectrum of acute COVID-19 severity. Methods: Observational cohort study of 4 groups; hospitalised, community illness with on-going symptoms (community-symptomatic), community i...

Objective Headache is the predominant disabler in idiopathic intracranial hypertension (IIH). The aim was to characterise headache and investigate the association with intracranial pressure. Methods IIH:WT was a randomised controlled parallel group multicentre trial in the United Kingdom investigating weight management methods in IIH. Participants...

Cognitive impairments have been reported in idiopathic intracranial hypertension; however, evidence supporting these deficits is scarce and contributing factors have not been defined. Using a case-control prospective study, we identified multiple domains of deficiency in a cohort of 66 female adult idiopathic intracranial hypertension patients. We...

Introduction Raised intracranial pressure (ICP) causes significant morbidity and mortality in a range of conditions including idiopathic intracranial hypertension (IIH) and traumatic brain injury (TBI). Exenatide is a GLP-1 receptor agonist; pre-clinical data demonstrates its ability to reduce ICP. GLP-1R agonists have also been shown to have neuro...

Background: The Idiopathic Intracranial Hypertension Weight Trial (IIH:WT) established the efficacy of bariatric surgery as compared to a community weight management intervention in reducing intracranial pressure in active IIH. The aim of this cost-effectiveness analysis was to evaluate the economic impact of these weight loss treatments for IIH....

Objective: Headache is the predominant disabler in idiopathic intracranial hypertension (IIH). The aim was to characterise headache and investigate the association with intracranial pressure. Methods: IIH:WT was a randomised controlled parallel group multicentre trial in the United Kingdom investigating weight management methods in IIH. Participant...

Importance: Idiopathic intracranial hypertension (IIH) causes headaches, vision loss, and reduced quality of life. Sustained weight loss among patients with IIH is necessary to modify the disease and prevent relapse. Objective: To compare the effectiveness of bariatric surgery with that of a community weight management (CWM) intervention for the...

Background: Idiopathic intracranial hypertension (IIH) is a condition predominantly affecting obese women of reproductive age. Recent evidence suggests that IIH is a disease of metabolic dysregulation, androgen excess and an increased risk of cardiovascular morbidity. Here we evaluate systemic and adipose specific metabolic determinants of the IIH...

The understanding of raised intracranial pressure (ICP) is increasing with the directed use of intracranial telemetric ICP monitors. This case uniquely observed ICP changes by telemetric monitoring in a patient with idiopathic intracranial hypertension (IIH), who developed rapid sight-threatening disease. A lumbar drain was inserted, as a temporisi...

Background Idiopathic Intracranial Hypertension (IIH) is associated with significant morbidity, predominantly affecting women of childbearing age living with obesity. Weight loss has demonstrated successful disease-modifying effects, however the long-term cost-effectiveness of weight loss interventions for the treatment of IIH has not yet been esta...

Objective: 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. Metho...

Background The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) determines pre-receptor 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 co...

Importance There is an unmet need for noninvasive biomarkers of intracranial pressure (ICP), which manifests as papilledema that can be quantified by optical coherence tomography (OCT) imaging. Objective To determine whether OCT of the optic nerve head in papilledema could act as a surrogate measure of ICP. Design, Setting, and Participants This...

Background 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 p...

Background The mechanisms driving headache in Idiopathic Intracranial Hypertension (IIH) are not fully understood. Headache is the dominant driver for disability and typically has migraine-like characteristics. There are currently no evidence-based therapeutics for headache in IIH, and consequently this is an important unmet need. Case series We re...

Background 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 pa...

Treatment 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 tol...

Idiopathic intracranial hypertension (IIH) is characterised by raised intracranial pressure (ICP) and papilloedema in the absence of an identifiable secondary cause typically occurring in young women with obesity. The impact is considerable with the potential for blindness, chronic disabling headaches, future risk of cardiovascular disease and mark...

Treatment 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 tol...

Purpose of review: The current article appraises the recent developments in idiopathic intracranial hypertension (IIH), with particular attention to novel therapeutic avenues and advanced clinical assessment and monitoring with optical coherence tomography and telemetric intracranial pressure devices. Recent findings: The incidence of IIH is inc...

Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology, characterized by elevated intracranial pressure frequently manifesting with chronic headaches and visual loss. Similar to polycystic ovary syndrome (PCOS), IIH predominantly affects obese women of reproductive age. In this study, we comprehensively examined the systemic...

Supplementary figure -Supplemental material for Therapeutic lumbar puncture for headache in idiopathic intracranial hypertension: Minimal gain, is it worth the pain?

Supplementary table -Supplemental material for Therapeutic lumbar puncture for headache in idiopathic intracranial hypertension: Minimal gain, is it worth the pain?

This paper summarises the first consensus guidelines for idiopathic intracranial hypertension as an infographic. Following a systematic literature review, a multidisciplinary specialist interest group met and established questions relating to population, interventions, controls and outcomes (PICO). A survey was sent to doctors who manage idiopathic...

Background: Headache is disabling and prevalent in idiopathic intracranial hypertension. Therapeutic lumbar punctures may be considered to manage headache. This study evaluated the acute effect of lumbar punctures on headache severity. Additionally, the effect of lumbar puncture pressure on post-lumbar puncture headache was evaluated. Methods: A...

Background: The management of idiopathic intracranial hypertension focuses on reducing intracranial pressure to preserve vision and reduce headaches. There is sparse evidence to support the use of some of the drugs commonly used to manage idiopathic intracranial hypertension, therefore we propose to evaluate the efficacy of these drugs at lowering...

Background: Optical Coherence Tomography (OCT) imaging is being increasingly used in clinical practice for the monitoring of papilloedema. The aim is to characterise the extent and location of the Retinal Nerve Fibre Layer (RNFL) Thickness automated segmentation error (SegE) by manual refinement, in a cohort of Idiopathic Intracranial Hypertension...

Background Management of Idiopathic Intracranial Hypertension (IIH) aims to reduce intracranial pressure (ICP). Acetazolamide is the most commonly used drug, with class 1 evidence demonstrating modest improvement in patients with mild visual loss. Other drugs used include Topiramate, Furosemide, Amiloride and Octreotide, despite little mechanistic...

The full text can be found in the publications section in the following link: https://www.birmingham.ac.uk/staff/profiles/metabolism-systems/sinclair-alexandra.aspx

Title: Error in spectral domain optical coherence tomography measures of retinal nerve fibre layer thickness in idiopathic intracranial hypertension Background: Papilloedema, a key diagnostic criterion of idiopathic intracranial hypertension (IIH), is characterised by peripapillary retinal nerve fibre layer (RNFL) abnormalities on spectral domain o...

SD OCT RNFL scans should be systematically reviewed in IIH patients with papilloedema as automated segmentation values can be significantly inaccurate, especially in the superior retinal quadrant and in patients with moderate to severe papilloedema. Scans should be manually re-segmented to be clinically accurate and relevant to individual patient m...

Background: Idiopathic intracranial hypertension (IIH) is a condition with few effective management options. So far, there have been no randomized controlled trials evaluating new treatments in IIH. Objectives: The purpose of this paper is to outline the trial design for the Idiopathic Intracranial Hypertension Drug Trial (IIH:DT), assessing an...

SD OCT RNFL scans should be systematically reviewed in IIH patients with papilloedema as automated segmentation values can be significantly inaccurate, especially in the superior retinal quadrant and in patients with moderate to severe papilloedema. Scans should be manually re-segmented to be clinically accurate and relevant to individual patient m...

Introduction Effective treatments are lacking for idiopathic intracranial hypertension (IIH), a condition characterised by raised intracranial pressure (ICP) and papilloedema, and found primarily in obese women. Weight loss and lowering body mass index (BMI) have been shown to lower ICP and improve symptoms in IIH; however, weight loss is typically...

Current therapies for reducing raised intracranial pressure (ICP) under conditions such as idiopathic intracranial hypertension or hydrocephalus have limited efficacy and tolerability. Thus, there is a pressing need to identify alternative drugs. Glucagon-like peptide-1 receptor (GLP-1R) agonists are used to treat diabetes and promote weight loss b...

Background Posttraumatic headache (PTH) occurs in up to 82% of patients with traumatic brain injury (TBI). Posttraumatic stress disorder (PTSD) occurs in 39% of those with PTH. This study evaluates whether PTSD affects PTH disability. Methods Eighty-six patients with TBI were prospectively evaluated in a secondary care trauma center. Headache disa...

Idiopathic intracranial hypertension (IIH) is strongly associated with obesity. We aimed to utilise dual-energy X-ray absorptiometry (DEXA) to characterise fat distribution, and to evaluate change in fat mass and distribution following weight loss. IIH patients (n = 24) had a similar fat distribution to body mass index (BMI)– and gender-matched obe...

Idiopathic intracranial hypertension (IIH), a condition of raised intracranial pressure, is characterised by headaches and visual disturbances. Its pathogenesis is currently unknown; however, dysregulation of androgens may be implicated. Here, the authors present a case of a 22-year-old patient undergoing female-to-male (FTM) gender reassignment wh...

Current therapies for reducing raised intracranial pressure (ICP) in conditions such as idiopathic intracranial hypertension (IIH) have limited efficacy and tolerability; therefore there is an urgent need to develop novel therapies. Glucagon-like peptide-1 receptor (GLP-1R) agonists are used therapeutically to treat diabetes and promote weight loss...

Objective: The aim of this study was to identify the most appropriate rehabilitation outcome measure for use in a young adult population with acquired brain injury. Methods: A 2-year prospective study of patients admitted to a UK military neuro-rehabilitation unit with acquired brain injury to compare the appropriateness of the Functional Indepe...

The Neuro-Rehabilitation Group at the Defence Medical Rehabilitation Centre (DMRC) has developed an integrated vocational pathway to transition service personnel back into employment. This article describes how vocational rehabilitation at DMRC fits with the wider UK military, in comparison with civilian rehabilitation. It also describes the ongoin...

Background and Aim The Golden Hour project aims to identify biomarkers that could assist in characterising traumatic brain injury (TBI) and predicting patient outcomes. When evaluating the outcome of TBI patients it is important to compare with patients of other injuries to account for the generic effect of trauma. This study compared the neuropsyc...

The effect of idiopathic intracranial hypertension (IIH) on quality of life (QOL) is poorly understood. Our objectives were to compare QOL in IIH to the normal UK population; to investigate QOL changes with treatment of IIH, using a weight loss intervention, and to determine which clinical factors influence QOL. This was a prospective cohort evalua...

Serial electrophysiology has been suggested as essential for accurate diagnosis in Guillain-Barré syndrome (GBS). However, whether more adapted electrophysiological criteria may allow a single study to be sufficient is unknown. We retrospectively reviewed records of 365 consecutive patients with GBS from Birmingham, UK, and Garches, France, admitte...