Prediction & Mechanisms of Recovery Following IEDS

Inner Ear Decompression sickness (IEDS) accounts for 20% of all types of decompression sickness (the bends) in divers. The condition commonly affects the peripheral vestibular system (inner ear). IEDS results in acute symptoms of dizzyness (vertigo) and imbalance. Even with the recommended treatment of hyperbaric oxygen therapy some people do not recovery fully. However, even in the presence of a permanent vestibular deficit many people can show a behavioural recovery where symptoms improve over time. Recovery can be aided by vestibular rehabilitation (VR) which is now routine for acute IEDS but was not provided before 2021, and is not widespread across the UK (United Kingdom) or world, meaning people may have a suboptimal recovery.

This project will investigate if and how people recover after an acute episode of IEDS and whether people who had IEDS in the past show changes in the central (brain) processing of vestibular function and in symptoms of dizziness, balance and posture.

This project has two main parts. Part one is a prospective observational study where people with an acute onset of IEDS are serially monitored while they are receiving hyperbaric treatment and VR over 10-14 days. Part two is a retrospective observational study where who have had IEDS in the past 15 years are re-assessed in a one-off session. The tests in both parts involve clinical tests and specialist eye movement recordings that assess vestibular function. We will also determine the site of any vestibular pathology by using selective stimulation of the vestibular end organ or nerve and assess whether there are any changes in how the structure and function of central vestibular pathways in the brain. In people with chronic IEDS with vestibular symptoms we will offer participants a course of VR over 12 weeks and assess whether this is associated with any improvement in symptoms.

Decompression sickness after diving can occur following a rapid ascent. Here, nitrogen, absorbed by the body when breathing compressed air at depth, comes out of solution and forms microbubbles in the blood. Inner ear decompression sickness (IEDS) accounts for approximately 20% of all cases of decompression sickness. The vestibular system is involved in \~85% cases of IEDS resulting in symptoms of vertigo, nausea, vomiting and unsteadiness with hearing loss and tinnitus.

The strong association of IEDS with a patent foramen ovale (50-73% of cases) suggests that a shunted venous gas embolism causes damage to the vestibular apparatus, which is particularly vulnerable due to its low perfusion and thus slow inert gas washout, compared to the cochlea and other brain structures. It is hypothesised that the nitrogen bubbles within the blood vessels trigger an inflammatory reaction in the endothelium with a coagulation cascade that leads to hypoxic injury and/or that there is direct damage to the membranous labyrinth. Animal models of rapid decompression suggest that it can cause a haemorrhage within the labyrinth with ectopic bone growth and fibrosis occurring over the next month. Advances in the imaging of the inner ear using a gadolinium-based contrast agent (GBCA) allow us to explore structural changes in human divers. Imaging can also help to differentially diagnose another potential cause of diving induced dizziness, superior structural dehiscence syndrome

Decompression sickness and the subsequent inflammatory response requires emergency treatment using with hyperbaric oxygen. The effects of hyperbaric therapy and rehabilitation are not uniform across participants, factors affecting recovery include a high clinical score on admission and a delay in hyperbaric recompression of over 6 hours. Complete recovery is seen in only about 30% of cases. Previous studies have highlighted that people who do not fully recover can have a variety of symptoms that can affect work, hobbies and well-being. These include feelings of instability in some situations (working at a height and with movement) and imbalance in the dark or when changing position.

In people with permanent vestibular pathology, symptoms can still improve due to central adaptive processes within the brain termed vestibular compensation. Clinical studies in other types of peripheral vestibular dysfunction show that it is possible to facilitate the compensation process and symptom recovery through vestibular rehabilitation. Early access to vestibular rehabilitation is now routine practice at the Diving Diseases Research Centre (DDRC) where patients are treated in the South-West UK. This is coupled to diagnosis and monitoring of vestibular function using objective laboratory tests (rotary testing) and clinical tests.

Animal studies highlight the mechanisms underlying vestibular compensation following a peripheral nerve lesion. These focus on changes in the interconnections between brainstem nuclei (e.g. vestibular nuclei) and the cerebellum and re-weighting of the relative importance of multi-sensory sensory inputs. Human studies in chronic peripheral dysfunction also suggest there are recovery-related changes in cortical areas that normally process vestibular information over time. Functional changes in the acute stages include an increase in contralesional activity in the parietoinsular vestibular cortex as well as interlinked subcortical areas (posterolateral thalamus, anterior cingulate gyrus, pontomesencephalic brainstem, hippocampus) with a decrease in activity was seen in the visual, somatosensory and auditory cortices. Structural changes over the first 3 months post lesion include increases in grey matter volume in the vestibular cortex, bilateral hippocampus, visual cortices and the cerebellum.

Within the DDRC vestibular rehabilitation has only been routinely undertaken for people diagnosed with IEDS since 2021. As complete recovery is seen in only about 30% of cases \[9\]; this suggests that there may be a cohort of patients with residual vestibular symptoms. In surveys of the aural and vestibular effects of diving, including those conducted by the DDRC, 79% (of 790 respondents) have reported aural related problems after learning to dive. Of those with reported problems 46% did not seek any medical advice and 39% specifically reported dizziness / vertigo. In total this suggests that at least 14% of all divers may have undiagnosed vestibular problems that could benefit from vestibular rehabilitation. A case review highlights that since 1999 there have been 79 cases of clinically diagnosed IEDS at the DDRC. Therefore, there is a need to assess and provide rehabilitation support to people with past IEDS and potentially in the future a larger cohort of divers with previously undiagnosed symptoms.

This study plans to:

undertake a prospective observational study where people with acute onset IEDS are followed up. This will include the current battery of clinical and laboratory (rotary) tests but also additional optional clinical and physiological testing (Vestibular Evoked Myogenic Potentials VEMPs), imaging (Diffusor Tensor Imaging DTI and functional Magnetic Resonance Imaging f MRI) and semis-structured interviews in the acute (1-14 days) and chronic (3 months and 12 months) stage.

We will also:

undertake a retrospective cross-sectional study of people who have previously been managed for IEDS by the DDRC. Here we will undertake the same battery of tests as for the prospective study which includes measures of potential risk factors and patient reported outcome measures. We will also take this opportunity to explore people's symptoms post IEDS and their views on future rehabilitation trials. In those with remaining vestibular symptoms and signs we will provide advice on vestibular rehabilitation by qualified personnel with follow up as required. We will compare our data to a cohort of healthy controls of a similar age and gender distribution.

Eligibility Criteria:
Prospective Study :

Inclusion

• Divers admitted with suspected IEDS

Exclusion

* Medically unstable
* Unstable orthopaedic deficits

Retrospective study :

Inclusion

• Divers diagnosed with IEDS at DDRC within past 10 years

Exclusion

• We will include all co-morbidities as these could affect prognosis and recovery following IEDS.

Healthy control comparator group :

Normative data will be gathered on an age matched group. There will be at least 10 participants for each decade (\<30yrs ,30-40yrs, 40-50 yrs,50-60yrs,60-70 yr.)

Inclusion criteria:

• Adults over 18 years

Exclusion criteria:

• Neurological, sensory or orthopaedic conditions that could affect balance.