assessing vestibular function in patients with stickler syndrome

Innovation and excellence in health and care Addenbrooke’s Hospital I Rosie Hospital

Assessing Vestibular Function in Patients with Stickler Syndrome using

vHIT. Keiran Joseph

Dr David Baguley

Dr Kai Uus

Learning Outcomes

• What is Stickler Syndrome?

• Why should we be interested in vestibular function in Stickler syndrome?

• What is the functionality of the peripheral vestibular system in Stickler syndrome?

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Background – Stickler Syndrome

• Stickler syndrome is a genetic disorder impairing the synthesis of collagen throughout the body thought to effect 1/7,500 – 1/9,000 newborns (Robin et al, 1993).

• First described by Stickler et al. (1965) Stickler syndrome is characterised by Ocular, Skeletal and Orofacial abnormalities.

Gunner Stickler and a Giant Retinal Tear courtesy of Wendy Hughes, President of Stickler Syndrome Society

Genetics

• Currently mutations in 5 genes are known to cause Stickler syndrome and thus 5 distinct types exist.

Mutation Prevalence Inheritance COL2A1 (Type 1) 80-90% Dominant COL11A1 (Type 2) 10-20% Dominant COL11A2 (Type 3) Rare Dominant COL9A1 (Type 4) Rare Recessive COL9A2 (Type 5) Rare Recessive

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Audiological Involvement – Audiometry

• Hearing loss affects 63% of people with Sticklers syndrome and is thought to be attributable to collagen deficiencies throughout the inner ear, middle ear and tympanic membrane (Khetarpal et al, 1994; McGuirt et al, 1999; Stenfeldt et al, 2006;

Knutsson et al, 2009), Acke et al, 2012). .

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• The prevalence of hearing loss varies between types but can be mixed, sensorineural or conductive.

Audiological involvement – Tympanometry

• Hyper-compliant tympanograms are identified in up to 46% of Stickers as their tympanic membranes lack structural collagen (Acke et al, 2012).

• This lack of collagen is also responsible for greater risk of longstanding perforation.

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But what do we know about the vestibular system?

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So should vestibular function be an issue?

• Collagen is present throughout the vestibular system in the Macula, the SSC membrane, the Ampulla and the Endolymphatic duct (Ishibe et al. 1989; Slepecky et al. 2009; Yoo and Tomoda, 1988).

• Complaints of imbalance are common but often

attributed to skeletal or ocular abnormalities and have rarely been investigated further (Acke et al, 2012).

• Peripheral vestibular dysfunction has been demonstrated in the phenotypically very similar Marshall Syndrome (Griffith

et al, 2000; Griffith et al, 1998).

Current understanding

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Scoping Exercise

• Bespoke questionnaire distributed to the UK and US Stickler societies as a scoping exercise. 69 patients responded; some interesting figures:

• Occurring Monthly or more: – 40% spontaneously have a spinning sensation – 66% have a spinning sensation with head movement

• Of those who are dizzy, 64% said it interferes with their

work, social or recreational life at least some of the time

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Scoping Exercise: Quotes

• “Turning head quickly as in changing lanes in traffic, getting out of bed some mornings or in the middle of night… I have to sit quietly on the edge of bed until it gets better”

• “Sudden movements of any kind does it very easily”

• “One episode was frightening - when I opened my eyes everything was spinning at a very fast velocity”

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How do we assess Vestibular function?

• Bi-thermal caloric irrigation is the current ‘gold standard’ in assessing peripheral vestibular function but are frequently contraindicated in Stickler patients because of the tympanic membrane abnormalities.

• Rotatory chair testing could have been possible but I do not have access to the equipment.

• VEMPs could also have been an option but as a number of Stickler patients have a conductive element to their hearing loss these would have been unfeasible in the majority of cases.

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Slide courtesy of Matthew Murray (GN Otometrics)

Assessment of Vestibular function - vHIT

• The video head impulse test measures the vestibulo-ocular reflex by tracking pupil movement relative to head movement and can be carried out in all 6 vestibular canals.

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Special thanks to GN Otometrics for loaning the equipment and the images.

• The results are then analysed and the gain displayed for interpretation.

Assessment - Other

• A concise clinical history to identify main (if any) vestibular complaints and to check for contraindications.

• Audiometry and tympanometry were carried out to assess for correlations with hearing loss

• DHI – to assess any correlation between impaired vestibular function and resultant dizziness handicap.

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Design and Procedure

• Ethical approval was given by Cambridge Central REC.

• Stickler patients attend an annual Ophthalmology review at Addenbrookes. All of those fitting the inclusion criteria with Ophthalmology appointments during the data collection were invited to participate.

• I have tested 17 participants to date. – 8 Male, 9 Female – 10 Type 1, 7 Type 2 – Median age 45, Range 27-71

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Research Questions

1. What is the incidence of abnormal peripheral vestibular function in Stickler syndrome?

2. Is there a difference in the incidence of abnormal peripheral vestibular function between the different types (gene mutations)?

3. Is the incidence of abnormal peripheral vestibular function related to hearing loss?

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Provisional vHIT and DHI results

• Of the 17 tested only 1 has had an abnormal vHIT result. – 38 Y/O female with type 1 Stickler syndrome – Has had bouts of TRV in the past with an ear infection – Gain of 0.65 (>0.7 is normal) in the right anterior SSC

• 1 Unable to complete testing because of severe Ptosis

• vHIT was normal in the remaining 15 participants but 5

scored significant on DHI. 2 were type 1 and 3 were type 2, when combined with the vHIT results, no clear genotypic susceptibility is highlighted.

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vHIT Display of Significant patient (P2)

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Covert Saccades

Provisional Audiometry results

• Audiometry (FFA >20dB = Hearing loss) – 3 Normal Hearing – 1 Unilateral SNHL – 3 Mixed one sided and SNHL the other - 1 Abnormal – 4 Bilateral SNHL – 2 Abnormal – 1 Bilateral CHL – Abnormal – 4 Bilateral Mixed - 2 Abnormal

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Provisional Tympanometry results

• Tympanometry – 7 Normal Tympanometry – 3 Abnormal – 3 Hyper-complaint (>3cm3) -1 Abnormal – 1 Perforation – 1 Flat – Abnormal – 5 Negative beyond -150daPa – 1 Abnormal

Trends: • 10/17 contraindicated for calorics • No obvious trend with Tympanometry and predicting

abnormal vHIT or significant dizziness handicap.

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Summary

• Only 1/ 17 demonstrated reduced gain on vHIT but a further 5 showed a handicap on the DHI.

• No obvious trend for one genotype to be more susceptible emerged

• All of those with reduced gain or significant DHI had a hearing loss.

• 10/17 were contraindicated for calorics based on tympanometry alone.

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Why the Mismatch?

• Though vHIT results are mainly normal, some histories suggest peripheral vestibular involvement: Why the Mismatch? – vHIT testing is not sensitive enough.

– Perhaps vHIT is not the complete test. – The dizziness may not be vestibular at all.

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Learning outcomes – Reviewed

• What is Stickler Syndrome?

• Why should we be interested in vestibular function in Stickler syndrome?

• What is the functionality of the peripheral vestibular system in Stickler syndrome?

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Acknowledgements

• Mr Martin Snead and team (Cambridge University Hospital)

• Matthew Murray and David

Smithson (GN Otometrics)

• Dr David Baguley (Cambridge University Hospital)

• Dr Kai Uus (University of Manchester)

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