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?

Innovation and excellence in health and care


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


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). .


• 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.


But what do we know about the vestibular system?



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


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


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”


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.



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.


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.


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


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?


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.


vHIT Display of Significant patient (P2)


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


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.


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.


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.


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?


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)


Assessing Vestibular Function in Patients with Stickler Syndrome

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