Alexandra J Sinclair

• MBChB (Hons) MRCP PhD
• Medical Professional at University of Birmingham

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...

Introduction There is limited longitudinal data evaluating visual and headache outcomes in Idiopathic intracranial hypertension and large prospective studies are required. Aims and Methods To evaluate the disease course for non-surgical IIH patients, determined by their pres- entation to neuro-ophthalmology with active IIH (papilloedema present) ve...

Introduction Idiopathic intracranial hypertension (IIH) and Polycystic ovary syndrome (PCOS) affect women of reproductive age with obesity but have different hyperandrogenic profiles. The prevalence of comorbid PCOS in IIH patients is highly variable in the literature; and the longitudinal impact on visual and headache outcomes are unknown. Aims a...

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...

We aimed to evaluate adjusted hazard ratio (aHR) for new-onset headache as well as headache medi- cation prescribing, opiate use and headache burden in women with idiopathic intracranial hypertension (IIH) compared to matched women with migraine and population controls. Data from IQVIA Medical Research Data, an anonymised, nationally representative...

Incidence rates for depression and anxiety has not been previously evaluated in a large matched cohort study in idiopathic intracranial hypertension (IIH). We analysed data collected between January-1995 and September-2019 from IQVIA Medical Research Data, an anonymised and nationally representative UK database. Crude incident rates for depression...

Introduction IIH is a known metabolic neuro-ophthalmologic disorder which is associated with body weight gain. A common reason for increasing weight in child-bearing aged women is pregnancy. The long-term impact of IIH diagnosed during pregnancy is not known. Aims and Methods Evaluate key outcomes such as visual acuity, visual fields, optical cohe...

Introduction Idiopathic intracranial hypertension (IIH) predominantly affects women of reproductive age with obesity with a distinct profile of hyperandrogenism and insulin resistance. Polycystic ovary syndrome (PCOS) has an established adverse fertility phenotype that typically affects obese women. IIH may impact reproductive health. Methods Pros...

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 Enforced national lockdown due to COVID-19 limited access to medical services. We evaluated the impact on those presenting with papilloedema, and those with a pre-existing diagnosis of idiopathic intracranial hypertension. Design A single United Kingdom centre prospective cohort study between May 15, 2020 (start of emergency clinics aft...

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: Cerebrospinal fluid (CSF) shunting in idiopathic intracranial hypertension (IIH) is associated with high complication rates, primarily because of the technical challenges that are related to small ventricles and a large body habitus. In this study, the authors report the benefits of a standardized protocol for CSF shunting in patients w...

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...

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...

The first lockdown impacted papilloedema and IIH patients significantly. There was a marked increase CSF diversion rate and weight gain. https://jnnp.bmj.com/content/early/2020/12/23/jnnp-2020-325519

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...

Idiopathic Intracranial Hypertension (IIH) is a debilitating disorder characterised by raised intracranial pressure (ICP), papilloedema with the potential risk of permanent visual loss, and headaches that are profoundly disabling and reduce the quality of life. The first consensus guidelines have been published on investigation and management of ad...

Polycystic ovary syndrome (PCOS) affects 10% of women and is a lifelong metabolic disorder, with increased risk of type 2 diabetes, fatty liver and cardiovascular disease. Androgen excess is an important driver of metabolic risk. Excess androgen activation in adipose tissue from PCOS women, through conversion of androstenedione (A4) to testosterone...

Objectives To quantify the hospital burden and health economic impact of Idiopathic Intracranial Hypertension. Design Observational cohort study. Subjects All those within England with a diagnosis of Idiopathic Intracranial Hypertension were included. Methods Hospital Episode Statistics (HES) national data was extracted between 1 st January 2002...

Objectives The aim was to capture interdisciplinary expertise from a large group of clinicians, reflecting practice from across the UK and further, to inform subsequent development of a national consensus guidance for optimal management of Idiopathic Intracranial Hypertension. Design Consensus guideline critically reviewed by the Association of Br...

Aim: Demographic factors potentially influencing the presentation and severity of idiopathic intracranial hypertension (IIH) in the US vs. UK populations include obesity and ethnicity. We aimed to compare the presenting features of IIH between populations in the UK and US tertiary referral centres, to assess what population differences exist and w...

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...

The multi-specialty approach to managing patients with cerebrospinal fluid (CSF) disorders requires neurology, neurosurgery, neuroradiology and neuro-ophthalmology. The annual United Kingdom CSF disorders meeting presented the first guidelines for idiopathic intracranial hypertension focusing on protecting the vision, managing the underlying diseas...

The evaluation of an isolated third cranial nerve palsy can be difficult and dangerous. The choices for initial imaging of a third nerve palsy is challenging in part because of the number of potential neuroimaging choices (e.g., magnetic resonance angiography (MRA), computed tomography angiography (CTA), intra-arterial digital subtraction angiograp...

This book offers an overview on the most recent advances in global neuro-opthalmic care. Global variation in the incidence and prevalence of specific neuro-ophthalmic conditions results in geographic differences in differential diagnosis, evaluation, management, and treatment of specific disorders. It covers a variety of disorders from optic neurit...

Purpose of review: To review the most relevant developments in the understanding of headache in idiopathic intracranial hypertension (IIH). Recent findings: The phenotype of the typical IIH headache is diverging from the historical thinking of a raised intracranial pressure headache, with the majority being classified as having migraine. A large...

Objective: To quantify the hospital burden and health economic impact of idiopathic intracranial hypertension. Methods: Hospital Episode Statistics (HES) national data was extracted between 1st January 2002 and 31st December 2016. All those within England with a diagnosis of idiopathic intracranial hypertension were included. Those with secondar...

Background: Idiopathic Intracranial Hypertension (IIH) is characterized by an elevation of intracranial pressure (ICP no identifiable cause. The aetiology remains largely unknown, however observations made in a number of recent clinical studies are increasing the understanding of the disease and now provide the basis for evidence-based treatment s...

Aims and methods Patients with idiopathic intracranial hypertension (IIH) often report significant morbidity associated with lumbar punctures. We therefore aimed to assess the patient’s experience of diagnostic lumbar puncture (LP) in IIH using an online survey designed in collaboration with IIH: UK (a leading UK charity). Results 463 patients res...

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: Traditional risk factors associated with idiopathic intracranial hypertension (IIH) include obesity, weight gain, and female sex. The incidence of IIH is increasing and yet the underlying trigger and the fueling pathological mechanisms are still poorly understood. Evidence acquisition: Review of ophthalmology, neurology, general surg...

Background: Migraine occurs in around 15% of adults and is ranked as the seventh most disabling disease amongst all diseases globally. Despite the available treatments many people suffer prolonged and frequent attacks which have a major impact on their quality of life. Chronic migraine is defined as 15 or more days of headache per month, at least...

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...

Methods: Between September 2015 and October 2017, a specialist interest group including neurology, neurosurgery, neuroradiology, ophthalmology, nursing, primary care doctors and patient representatives met. An initial UK survey of attitudes and practice in IIH was sent to a wide group of physicians and surgeons who investigate and manage IIH regul...

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...

Objectives Patients with idiopathic intracranial hypertension (IIH) usually require multiple lumbar punctures (LPs) during the course of their disease, and often report significant morbidity associated with the procedure. The aim of this study was to assess the patient’s experience of diagnostic LP in IIH. Design, methods and participants A cross-...

The management of patients with cerebrospinal fluid disorders requires a multi-specialty approach involving specialists in neurosurgery, neurology, neuroradiology and neuro-ophthalmology. A symposium on CSF disorders was organised by the clinical and academic teams at University Hospitals Birmingham, United Kingdom. The meeting featured a synopsis...

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...

The management of patients with cerebrospinal fluid (CSF) disorders requires a multi-specialty approach involving specialists in neurosurgery, neurology, neuroradiology, and neuro-ophthalmology. A symposium on CSF disorders took place at University Hospitals Birmingham and covered a selection of the more challenging and controversial issues facing...

Acetazolamide is one of the most widely used drugs for lowering intracranial pressure (ICP) and is believed to reduce cerebrospinal fluid (CSF) secretion via its action on the choroid plexus (CP). In the CP the main driving force for CSF secretion is primarily active transport of Na⁺ ions facilitated by the Na/K ATPase. Transmembrane water channels...

Idiopathic intracranial hypertension (IIH) is a condition characterised by raised intracranial pressure of unknown pathogenesis. Over 94% of sufferers are young, obese women, but little is known about their metabolic phenotype. Previous studies measuring waist-hip ratios in IIH have suggested predominant lower body adiposity. We aimed to characteri...

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...

Idiopathic intracranial hypertension (IIH) is a disorder of raised intracranial pressure (ICP) of unknown cause. This condition is primarily seen in obese females of childbearing age, a phenotype similar to that in polycystic ovary syndrome (PCOS). We aimed to characterise the androgen metabolic signature in IIH compared to PCOS and simple obese co...

Management of Idiopathic Intracranial Hypertension (IIH) is not standardised. A multidisciplinary Special Interest Group (SIG) was established to develop a uniform investigation and treatment strategy according to disease severity based on current literature and expert consensus. Methods A systematic literature review of “IIH”;“Benign IH” and “pse...

Online questionnaire of 463 IIH patients, assessing their experience of diagnostic lumbar punctures.

THE ANDRO-METABOLIC SIGNATURE OF IDIOPATHIC INTRACRANIAL HYPERTENSION COMPARED WITH POLYCYSTIC OVARY SYNDROME AND SIMPLE OBESITY. Authors: Catherine Hornby1, Michael O’Reilly2, Hannah Botfield1, Keira Markey1, Punith Kempegowda2, Angela Taylor2, Beverley Hughes2, Jeremy Tomlinson3, Wiebke Arlt2 and Alexandra Sinclair1 1Neurometabolism, Institute of...

CHARACTERISING FAT DISTRIBUTION AND RESPONSE TO WEIGHT LOSS IN IDIOPATHIC INTRACRANIAL HYPERTENSION. Authors: Catherine Hornby1, Hannah Botfield1, Michael O’Reilly2 , Keira Markey1, William Scotton1, Jeremy Tomlinson2,3, Wiebke Arlt2 and Alexandra Sinclair1,3 1Neurometabolism, Institute of Systems and Metabolism Research, University of Birmingham,...

Background In an effort to develop novel treatments for communicating hydrocephalus, we have shown previously that the transforming growth factor-β antagonist, decorin, inhibits subarachnoid fibrosis mediated ventriculomegaly; however decorin’s ability to prevent cerebral cytopathology in communicating hydrocephalus has not been fully examined. Fur...

Our study reveals the therapeutic potential of Decorin to attenuate hydrocephalus-induced changes in astrogliosis, oedema and demyelination particularly in the caudal periventricular white matter. Furthermore, diffusion tensor imaging is a useful tool to provide surrogate measures of periventricular white matter pathology in communicating hydroceph...

Background: Post-traumatic headache (PTH) occurs in up to 82% of patients with traumatic brain injury (TBI). Post-traumatic stress disorder (PTSD) occurs in 39% of those with TBI. This study evaluates whether PTSD affects PTH disability. Methods: 151 consecutive patients with TBI were evaluated from a secondary care trauma centre. Headache disabil...

Background The use of diffusion tensor imaging (DTI) to examine Decorin's ability to prevent cerebral cytopathology in communicating hydrocephalus is yet to be fully investigated. Hence, this study aimed to determine whether Decorin treatment influences alterations in DTI parameters and cytopathology in an experimental model of the disease. Method...

Context: Idiopathic intracranial hypertension (IIH) is characterised by elevated intracranial pressure and occurs predominantly in obese premenopausal women. Signs and symptoms of polycystic ovary syndrome (PCOS) often coexist in IIH. Here we compared the androgenic and metabolic phenotypes in IIH, PCOS and simple obesity. Patients and Methods: We...

There is increasing interest in using neurostimulation to treat headache disorders. There are now several non-invasive and invasive stimulation devices available with some open-label series and small controlled trial studies that support their use. Non-invasive stimulation options include supraorbital stimulation (Cefaly), vagus nerve stimulation (...

Idiopathic intracranial hypertension (IIH) results in raised intracranial pressure (ICP) leading to papilledema, visual dysfunction, and headaches. Obese females of reproductive age are predominantly affected, but the underlying pathological mechanisms behind IIH remain unknown. This review provides an overview of pathogenic factors that could resu...

Idiopathic intracranial hypertension (IIH) is a rare but important disease associated with significant morbidity. There is an expected rise in prevalence in line with the escalating global burden of obesity. Modern revisions in the terminology and diagnostic criteria for IIH help guide clinicians in investigations and researchers in standardising r...

Idiopathic intracranial hypertension is a disorder characterised by raised intracranial pressure that predominantly affects young, obese women. Pathogenesis has not been fully elucidated, but several causal factors have been proposed. Symptoms can include headaches, visual loss, pulsatile tinnitus, and back and neck pain, but the clinical presentat...

We have shown previously that Decorin, by antagonizing TGF-β–mediated subarachnoid fibrosis, prevents ventriculomegaly in experimental juvenile hydrocephalus. To focus on white matter alterations, we sought to correlate cytopathological changes induced by hydrocephalus with diffusion tensor imaging (DTI) parameters and determine if Decorin could pr...

Headache is one of the most common conditions presenting to the neurology clinic, yet a significant proportion of these patients are unsatisfied by their clinic experience. Headache can be extremely disabling; effective treatment is not only essential for patients but is rewarding for the physician. In this first of two parts review of headache, we...

Background 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. Methods This was a pro...

To the Editor The Idiopathic Intracranial Hypertension Treatment Trial¹ evaluated the use of acetazolamide vs placebo in conjunction with a weight-reducing, low sodium diet in adults with idiopathic intracranial hypertension (IIH). Although the authors stated “there are no properly designed clinical trials,” the widespread use of acetazolamide has...

Background There have been no previous studies assessing quality of life (QOL) in idiopathic intracranial hypertension (IIH). Our previously published prospective cohort study confirmed that weight loss, significantly reduced intracranial pressure (ICP) and treated chronic active IIH. Method We assessed QOL using the short form 36 questionnaires (S...

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...

A 17-year-old girl presented with a 2-week history of increasingly severe generalised headache that was worse on waking, with blurring of vision and transient visual obscurations. Her visual acuity was 6/24 right eye and 6/36 left eye with a marked constriction of visual fields. Fundus examination showed severe optic disc swelling bilaterally with...

Adult patients who present with papilloedema and symptoms of raised intracranial pressure need urgent multidisciplinary assessment including neuroimaging, to exclude life-threatening causes. Where there is no apparent underlying cause for the raised intracranial pressure, patients are considered to have idiopathic intracranial hypertension (IIH). T...

Medication-overuse headache (MOH) is caused by the regular use of medications to treat headache. There has been a lack of research into awareness of MOH. We distributed an electronic survey to undergraduate students and their contacts via social networking sites. Analgesic use, awareness of MOH, perceived change in behaviour following educational i...

Idiopathic intracranial hypertension (IIH) is a condition characterised by increased intracranial pressure of unknown cause predominantly seen in obese women of childbearing age and associated with a history of recent weight gain. The aetiology is poorly understood and there are no evidence-based guidelines on the management of the disease. We aim...

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) interconverts the inactive glucocorticoid cortisone and its active form cortisol. It is widely expressed and, although bidirectional, in vivo it functions predominantly as an oxoreductase, generating active glucocorticoid. This allows glucocorticoid receptor activation to be regulated at a prerecep...

Evidence is emerging that migraine is not solely a headache disorder. Observations that ischemic stroke could occur in the setting of a migraine attack, and that migraine headaches could be precipitated by cerebral ischemia, initially highlighted a possibly association between migraine and cerebrovascular disease. More recently, large population-ba...

Optic disc appearance is a key measure of disease status in Idiopathic Intracranial Hypertension (IIH). Frisen classification describes stages of papilloedema (grades 0–5) and is used internationally, in clinical and research practice. No studies have evaluated Frisen classification since its original description. We assess the inter-rater reproduc...

Metabolomic analysis has the potential to generate disease-specific metabolite signatures unique to individuals. Autoimmune illnesses, such as inflammatory uveitis, have highlighted the discriminative power of metabolomics by allowing disease sub-classification. Elucidating surrogate markers for neurological disease is particularly important, given...