Investigating oculomotor and vestibular function in individuals with Rett syndrome

Rett syndrome (RTT) is a severe neurodevelopmental disorder predominantly
affecting females. It is characterised by the progressive loss of motor and
communication skills after seemingly near-normal development in the first year
of life, accompanied by stereotypic hand clapping behaviours and additional
features including abnormal breathing, scoliosis and epilepsy. Apraxia is one
of the significant features of the syndrome, affecting (amongst others) those
movements that are necessary to communicate in traditional ways such as through
speech, gesture and / or manual signs. Many individuals with RTT are thought to
understand more language than they are able to express. They are reported to
retain good eye pointing skills, which opens up a way to communicate through
eye gaze and/or eye tracking technology. However, not all individuals with RTT
succeed in their attempts to use eye gaze systems for communication and it is
unclear where points of breakdown lie.
It is hypothesised that neural and motor movements associated with eye gaze are
(relatively) less affected by apraxia than other pathways. To date, however,
the neural pathways shared by the oculomotor and vestibular systems have been
little researched in RTT. Investigation of these basic pathways prior to
introducing an eye gaze system for communication could indicate any underlying
problems which might hinder future success and could contribute towards
localisation of the problem for anyone already struggling to use such a system.
These same pathways may also be significant for the development of scoliosis in
adolescence in RTT. A link has been identified between oculomotor and
vestibular system dysfunction and amplitude of spine deformity in cases of
idiopathic adolescent scoliosis; such a relationship has not yet been explored
in RTT. Evidence of a link could have implications for therapy and
non-surgical, or at least pre-surgical, intervention which is significant in a
medically-vulnerable population.
The oculomotor and vestibular assessments routinely conducted by the Department
of Otorhinolaryngology (Division of Balance Disorders) at MUMC+ offer
potentially deeper insights into (1) neural pathways and motor activity
underpinning observable eye gaze/eye tracking behaviours in RTT, and (2) a
possible association between visuo-ocular and vestibulo-ocular responsivity and
scoliosis in RTT. These tests are already incorporated into the routine package
of clinical assessment offered to individuals with RTT within the context of
three-day inpatient brainstem registration. The aim now is to offer these same
oculomotor and vestibular assessments to individuals with RTT attending the
multidisciplinary outpatient clinic and to combine the results from both sets
of subjects for research as well as clinical purposes. Once established with
these groups a further aim is to invite the wider RTT community (via the Dutch
Rett Syndrome Association, the Dutch Rett Syndrome Foundation or speech and
language therapists) to participate in the assessments.
Collecting objective measures associated with neural pathways has a two-fold
benefit: firstly, at a clinical (individual) level, the assessments contribute
to the delineation of a more detailed profile of an individual*s skills and
needs which can inform planning of their interventions and therapy, improving
their personal quality of life; secondly, at a research (collective) level,
insight into the neural pathways can be collated anonymously to contribute to
the growing body of knowledge about RTT which can inform global recommendations
around intervention planning and therapeutic management, improving quality of
life for all individuals with RTT. These aims fit with the wishes expressed by
parents.

* To investigate oculomotor and vestibular activity in individuals with RTT.
* To compare oculomotor and vestibular activity with more functional eye gaze
and communication skills.
* To compare oculomotor and vestibular activity with severity of scoliosis.

Observational study

1. Individuals who come as an inpatient onto the PICU for three-day brainstem
registration:
The oculomotor, vestibular and functional communication assessments are already
established as part of the clinical routine during the three-day brainstem
registration. There is no added burden to subjects and families except that the
parents will be asked to take a little time (10-15 minutes) to complete a
questionnaire at home prior to the session, and the results from the
assessments will be used for research purposes in addition to providing
individual clinical data.

2. Individuals who come to the multidisciplinary outpatient Rett clinic for a
one-day consultation:
The oculomotor, vestibular and functional communication assessments will be
added to the investigations undertaken routinely during the multidisciplinary
clinic. The added burden will amount to one-two hours of added time on the day
of the clinic visit, and completion of a questionnaire at home prior to the
session (10-15 minutes).

3. Individuals who would not otherwise be coming to the hospital:
The time burden from participation in the study will amount to one-two hours*
attendance at the hospital in addition to travel time on the day of assessment
and completion of the questionnaire at home prior to the session (10-15
minutes).

In all cases, there will be no added psychological burden from completion of
the functional communication questionnaire or any additional communication
assessments. In order to protect the subjects and their families, the
parents/guardians will be asked to give informed consent for the use of their
data for research purposes and the data will be anonymised, the subject*s data
for research purposes and the data will be anonymised.