The UK CSF Disorders Day 2022

ABSTRACT

The annual United Kingdom cerebrospinal fluid disorders meeting made its return to the University of Birmingham, United Kingdom, following the break in proceedings due to the coronavirus pandemic. Cerebrospinal fluid disorders require a multi-disciplinary approach with inputs from the neurological, neuro-ophthalmological, neuroradiological, and neurosurgical specialities. The annual meeting presented the newest concepts underpinning idiopathic intracranial hypertension pathophysiology and the advances in intracranial pressure monitoring and treatment.

Introduction

The United Kingdom Cerebrospinal Fluid (CSF) conference invites members of the multidisciplinary team including neurology, neuro-ophthalmology, neuroradiology, and neurosurgery to compile and discuss the latest research, challenges, and controversial issues surrounding CSF disorders. The congress was designed and organised by Professor Susan Mollan, Consultant Neuro-ophthalmologist, University Hospitals Birmingham, and Professor Alexandra Sinclair, National Institute for Health Research (NIHR), Clinician scientist, Institute of Metabolism and Systems Research at University of Birmingham. The 2022 symposium’s aims were to facilitate multi-disciplinary discussion on the latest issues when faced with managing CSF disorders and working towards improving patient outcomes. The day provided a synopsis of the latest research and clinical trial findings of CSF disorders, in particular idiopathic intracranial hypertension (IIH) and hydrocephalus.

Research and quality improvement in CSF disorders

Dr Aimee Goel (Neurosurgical Trainee, University Hospitals Birmingham) was awarded the presentation prize for her research in the value of using endoscopic third ventriculostomy (ETV) success scores in predicting adult hydrocephalus outcomes following treatment. The current scoring system used was based upon paediatric data, with few studies validating its use in an adult population. A 9-year retrospective analysis found that planned procedures, obstruction at the level of the aqueduct, and aqueductal stenosis as a cause for the obstruction, all correlated with better outcomes post-ETV. The group were then able to develop a novel ETV success score from these factors, which was found to be more reliable than the previously used score (area under the curve 0.69 versus 0.65, respectively).

Mr Sebastiam Yim (Medical Student, University of Birmingham) also won a prize for his presentation of an audit investigating the impact of new local clinical guidelines on best practice for ventriculoperitoneal shunts (VPS). They were able to demonstrate that the distal end of a shunt inserted via a laparotomy approach was more common and had become more prevalent in the past 3 years. Laparoscopically sited shunts in this cohort were associated with lower revision and complication rates. Therefore, they recommended that the laparoscopic method may be the preferred surgical option in people with a higher body mass index (BMI).¹

Dr Mark Thaller (Masters Student, Translational Brain Science, University of Birmingham; Neurology Registrar, University Hospitals Birmingham) presented the IIH:Life study, which is a prospective cohort study evaluating the prognostic factors impacting the visual outcome in people with IIH. He was awarded the IIHUK prize for his work in IIH (Figure 1). His results showed that an elevated optical coherence tomography (OCT) retinal nerve fibre layer (RNFL) thickness greater than 400 µm was associated with worse visual outcomes. Interestingly, severe papilloedema was associated with macular ganglionn cell layer (GCL) thinning on OCT imaging, which often only became apparent 12–18 months after the initiation of treatment. This suggested that in the future we may need to consider early treatment of raised intracranial pressure (ICP) to minimise GCL thinning, which may be the precursor to visual field loss.²

Figure 1.

Dr Thaller (middle) is awarded the IIH UK prize for his work in IIH by Professors Sinclair (left) and Mollan (right).

Dr Yousef Hyder (Academic Clinical Fellow, University Hospitals Birmingham), presented a prospective cohort study to define the characteristics and prognosis of people with IIH who had required CSF shunt surgery. By 6 months, many patients reported the return of migraine-like headaches, despite resolution of papilloedema. This alludes to the many factors that may play a role in generating headaches following raised ICP.

Dr Gopiga Thanabalasundaram (Neurosurgical Trainee, University Hospitals Birmingham) presented improvements in shunt revision rates following implementation of a local protocol. Dr Mahmoud Samara (Neurosurgical Trainee, Queen Elizabeth Hospital, Birmingham; Institute of Metabolism and Systems Research, University of Birmingham) gave insights into the waveform characteristics of ICP in 62 patients with IIH who received primary VPS insertion. In particular, the team observed that, although patients may lose ICP pulsatility following their shunt surgery, this did not signify shunt dysfunction. Therefore, loss of pulsatility should not be an indication for a shunt revision. At the close of the trainee tournament Dr Andreas Yiangou (PhD Student and Academic Neurology Speciality Trainee, Queen Elizabeth Hospital, Birmingham) presented the work on identification of non-invasive biomarkers for raised ICP through Spectralis (Heidelberg Engineering) OCT imaging. Parameters of optic nerve head volume, central thickness, maximum height, and maximum central height in people with IIH correlated with ICP measurements.³

Latest in trials for CSF disorders

Ms Olivia Grech (Masters and PhD student, University of Birmingham) presented the results of IIH:Pressure, a randomised control trial, which evaluated cognitive function in people with IIH and the impact of five commonly used medications for IIH. All patients received discrete trials of furosemide, spironolactone, topiramate, amiloride, and acetazolamide, distributed sequentially with wash-out periods in between. Her results showed that topiramate, amiloride, and acetazolamide were associated with reduced cognitive function. In addition, people with IIH were more likely to have impaired cognition when compared with control groups, which improved once patients received treatment to reduce ICP. In particular, executive functioning, sustained attention, and working memory all improved at follow-up assessment 12 months following the start of ICP lowering treatment. Her conclusions may mean that the results of cognitively demanding tests such as visual field testing used early in IIH assessment may in fact be an unreliable as a result of cognitive deficit due to raised ICP.⁴

Dr Mark Thaller presented his work on maternal health in people with IIH. He described the positive finding of IIH being associated with pre-eclampsia, gestational diabetes, and reduced birth rate, which he concluded as a likely result of the dysregulated systemic metabolic phenotype which has been found in people with IIH.⁵ The presented data also implied that patients with IIH were more likely to give birth through assisted methods of delivery.⁶ Dr Thaller hypothesised that these decisions may be practitioner-led due to the fear of sustained raised ICP during the second stage of labour. He eloquently explained, with support of a graph demonstrating ICP levels during labour, that such decisions may be unnecessary as ICP quickly returns to normal following periods of pushing. Dr Thaller’s research in this matter offers insight into our understanding of IIH in pregnancy and will help aid clinicians in its future management.⁷

Mr Georgios Tsermoulas (Consultant Neurosurgeon, Queen Elizabeth Hospital, Birmingham) discussed recent evidence reporting the improving success of VPS, lumboperitoneal shunts (LPS), and dural venous sinus stents (DVSS) in the management of raised ICP. He observed that DVSS has been found to have superior outcomes in revision rates and improvement in papilloedema, visual function, and headaches, although the current literature has limitations for the interpretation of these results.⁸ Considering this, Mr Tsermoulas educated that stents may be less invasive and therefore preferable to shunts, highlighting his point by comparing examples of cerebral artery repair through open clipping versus endovascular methods. His reflections highlighted the need for more research comparing DVSS with their shunt counterparts. He introduced IIH Intervention, which is a Health Technology Assessment and a randomised control trial, which plans to evaluate DVSS and CSF shunting for visual loss in IIH and is due to start recruiting patients in the UK in the late Autumn 2022.⁹

Keynote speakers

Mr Ahmed Toma (Consultant Neurosurgeon, National Hospital for Neurology and Neurosurgery, Queen Square, London) was the first keynote speaker of the congress. He spoke on the normal physiology of CSF pressures and ventricular compliance in conjunction with the expected variation when changing between supine sitting and standing postures. Mr Toma elaborated on how there can be paradoxical increases in ICP when shunt valves are opened and vice versa when they are tightened, often leading to worsening symptoms when shunt settings are altered.¹⁰ He advised that telemetric ICP monitoring had helped his clinical practice to guide shunt management and detect those with shunt blockage.

Professor Alexandra Sinclair described how our perspectives of IIH aetiology have changed and evidence now points to IIH as a systemic metabolic disorder with features of truncal obesity, insulin resistance, and a distinct androgen excess profile. Observing that adipose tissue in patients with IIH is relatively primed for liponeogenesis, Professor Sinclair relayed the difficulty some patients encounter losing body weight needed to normalise ICP.¹¹ Following on, Professor Sinclair then discussed the results of a double blinded placebo RCT investigating the efficacy of exenatide, a glucagon-like peptide-1 receptor agonist, in IIH. The trial’s primary outcome showed promising results as exenatide was shown to have acute and longstanding efficacy when reducing ICP.¹² Exenatide was also found to reduce the frequency of headache days and improve visual acuity. Further phase 3 trials are becoming a reality.

Dr Mona Ghadiri-Sani (Consultant Neurologist, The Walton Centre, Liverpool) gave an informative talk on the chronic management of migraine in patients with IIH, with key points about anticipating medication overuse headache and the impact of preventative medications that may exacerbate weight gain.¹³ Whilst clarifying the underlying pathophysiology of trigeminal nerve activation, Dr Ghadiri-Sani noted the role of calcitonin gene-related peptide (CGRP) in migraine generation and its potential for therapeutics antagonising its effects. Three anti-CGRP medications (erenumab, fremanezumab, and galcanezumab) are licensed for episodic or chronic migraine in adults and they are likely to play a pivotal role in migraine management moving forward.

Mr Mike Potts (Neuro-Ophthalmologist and Oculoplastic Surgeon, Bristol Eye Hospital, UK) discussed the use of optic nerve sheath fenestrations (ONSF) in the management of CSF disorders. He stated that ONSFs appear to have fallen out of favour by UK clinicians over recent years,¹⁴ and suggested this may be due to the infrequent performance, incorrect approach, and inappropriately late referral for patients to fully benefit from the operation. Observing how technological advances have progressed other surgeries, Mr Potts suggested that cases of fulminant IIH may benefit from the minimally invasive approach of ONSF and that the orbit should still be a site from which we consider to drain CSF.

Professor Susan Mollan showcased the features of anomalous discs, describing how it can be difficult to distinguish between pseudo- versus actual papilloedema clinically, and how OCT imaging is able to differentiate between the two. She showed examples of how OCT imaging was now central to her practice and was useful in monitoring patients. OCT imaging could signpost the need for escalation of treatment, warning signs including a measured maximum height >1200 μm at the optic nerve head or the presence of subretinal fluid and intraretinal fluid. She also has observed that vessel oedema on the RNFL was a sign that the papilloedema would likely need surgical intervention.

The day saw neurosurgeons, ophthalmologists, neurologists, orthoptists, and nursing staff all benefiting from the friendly discussions with the aim of improving care of our patients with CSF disorders. The workshops in the afternoon were a particular hit (Figures 2–4), as were the posters, which saw work from all over the UK presented. IIHUK was thanked for their support of work in the field (Figure 5). In 2023, the UK CSF day will be in the Autumn (watch this website for details: https://www.hospitalcharity.org/shop/category/medical-courses).

Figure 2.

Mr Tsermoulas, Consultant Neurosurgeon, delivering one of the afternoon workshops in precision shunt surgery.

Figure 3.

The direct ophthalmoscopy skills workshop run by Dr Ahoane Qureshi, Clinical education fellow at University Hospitals Birmingham.

Figure 4.

Mr Nick Capewell and Mrs Donna Holding take questions in their workshop on excellence in collecting visual data.

Figure 5.

Professors Mollan and Sinclair thank Shelly Williamson, the chairperson of IIHUK (registered patient charity number 1143522), for IIHUK’s support of the meeting and contributions towards the IIH:Life study (ethically approved by National Health Service National Research Ethics Committee [14/LO/1208]).

Funding Statement

The authors reported that there is no funding associated with the work featured in this article

Disclosure statement

EB reports no conflicts of interest. AJS reports personal fees from Invex Therapeutics during the conduct of the study as well as share option and shareholdings, speaker fees (Novartis; Allergan; Teva UK) and consulting fees (Allergan; Chiesi; Novartis; Lundbeck). SPM reports consultancy fees (Invex Therapeutics); advisory board fees (Invex therapeutics; Gensight); and speaker fees (Heidelberg engineering; Chugai-Roche Ltd; Allergan; Santen; Teva UK; Chiesi; and Santhera).