Using connectomes for individualised deep brain stimulation in essential tremor

Essential tremor (ET) is the most common movement disorder. ET can be severely
disabling and is medication-resistant in about half of patients. Deep brain
stimulation (DBS) can spectacularly improve symptoms in medication-refractory
patients. In DBS, electrodes are implanted in the brain providing electric
current to surrounding brain tissue. The DBS target for ET is a white matter
bundle called the dentatorubrothalamic tract, which connects the cerebellum and
thalamus. Although DBS can be an effective treatment, its use is severely
limited in one-third of patients due to troublesome DBS-related side-effects
such as ataxia (coordination and balance difficulties). This is caused by
unintentional spilling of electric current into adjacent structures. Current
DBS programming is based on basic flowcharts supplemented with the effects of
certain settings in a trial-and-error setting. This is inefficient and often
ineffective.

Identify the functional and structural connectomes related to tremor control
and to DBS-induced ataxia in patients with ET. The aim of the FINEST study is
to improve the treatment of patients with ET and DBS-induced ataxia, by using
the connectome for individualised DBS. During this study the connectome will be
identified. In a follow-up study (not part of this protocol) the tolerability
of connectome-guided DBS settings will be assessed, and the effectiveness of
connectome-guided DBS will be tested in a randomised crossover trial.

Cross-sectional observational study.

Participants will undergo one study visit. The visit will take about 4,5 hours
and consists of a morning and afternoon part. The morning part of the protocol
consist of a clinical evaluation with DBS ON and OFF (DBS-OFF and DBS-BASELINE)
and a bipolar review for ataxia assessment (DBS-ATAXIA). Different neurological
tests and switching off the DBS stimulator are standard procedures in the
department. For DBS-ATAXIA, side-effects such as speech, coordination and gait
difficulties will be induced by specific DBS settings. This can cause temporary
discomfort for the patient. If settings are not tolerated, they can be changed
acutely to settings that are tolerated by the patient. During these
assessments, video recordings and tremor recordings using kinematic sensors
will be collected. This will take up 3 hours. After a half-hour break we will
continue with the afternoon session. During a 1 hour afternoon session, the 3
different DBS settings (DBS-OFF, DBS-BASELINE and DBS-ataxia) will be tested
during 6.5 minute scan sessions. The proposed investigations bear virtually no
risks and are expected to be well-tolerated. The use of the DBS system in
'MRI-mode' during the MRI acquisition is on-label. All safety requirements
regarding DBS in an MR-environment will be met in accordance with the clinical
physicists responsible for the MRI (see chapter 11 for an elaborate structured
risk analysis). There is a small risk for uncovering coincidental findings on
MRI-imaging. This risk is judged to be small considering the fact patients have
already undergone pre-operative MRI for DBS work-up. Relevant coincidental
findings should therefore have already been picked up before study
participation. Clinically relevant coincidental findings will be communicated
with the patient, the general practitioner and/or treating neurologist/nurse
practitioner. Due to the very specific aim of this study, only patients
suffering from severe tremor and are being treated with DBS can participate.
There is no direct benefit from this study for the participants.