a) Identification of stimulation site-specific functional and structural brain network characteristics in patients with PD and STN-DBS.b) Relating subject-specific stimulation sites and functional network changes to measures of cognitive and…
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
- Nervous system, skull and spine therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are stimulation site-specific neurophysiological
measures, as obtained by MEG recordings, and individual differences in the
exact locations and structural connections of each stimulation site, as
obtained by pre- and post-DBS brain imaging. These network parameters will be
correlated with clinical measures of cognitive and psychiatric side effects.
Secondary outcome
N.a.
Background summary
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective
surgical intervention for motor symptoms in Parkinson*s disease (PD), but it
can induce negative cognitive and psychiatric side effects in up to 25% of
patients. Usually the electrodes targeted at the STN are implanted bilaterally.
Each electrode may have four or eight contact points. Clinical improvement and
side effects differ per stimulated contact point, but the cause of these
effects is only partly understood. At present, it may take months to identify
the optimal DBS settings via trial and error. Stimulation of white matter
tracts surrounding the STN is considered important for the clinical effects of
DBS. The relationship between contact points and white matter tracts, hence the
stimulation sites, can be approximated using diffusion tensor imaging (DTI).
Magnetoencephalography (MEG, a recording of magnetic fields related to brain
activity) can be used to characterize stimulation site dependent functional
networks that can be associated with the occurrence of (side) effects. The
combination of contact point-specific functional and structural brain network
characteristics can help to identify stimulation sites prone to induce side
effects. This could improve clinical outcome by aiding DBS electrode placement
and contact point selection.
Study objective
a) Identification of stimulation site-specific functional and structural brain
network characteristics in patients with PD and STN-DBS.
b) Relating subject-specific stimulation sites and functional network changes
to measures of cognitive and psychiatric side effects.
Study design
This explorative study is an observational, cross-sectional study using MEG to
characterize stimulation site-specific functional brain network
characteristics. The functional networks will be obtained by alternatingly
stimulating individual stimulation sites. This will be combined with clinical
data from the Academic Medical Center (AMC) Amsterdam, where patients have
undergone STN DBS. In the context of standard clinical care, pre- and post-DBS
neuroimaging and evaluation of cognitive side effects will be conducted.
Pre-DBS assessment of psychiatric symptoms takes place in the context of
standard clinical care as well, whereas post-DBS information on psychiatric
side effects will be obtained using questionnaires in anticipation of- and
during the study visit for MEG recordings at VUmc.
Study burden and risks
MEG recordings are non-invasive, pain free and have negligible risks. Based on
literature and our own experience in a pilot study, MEG recordings during DBS
are a safe procedure. Participants will make one extra trip to the VUmc for the
study visit. Changing DBS settings within the limits stated in the individual
DBS passport of the participants is a risk-free procedure. As participants are
in supine position on a comfortable bed during MEG recordings, we do not expect
them to experience unacceptable motor symptoms. Although participants do not
directly benefit from this exploratory study, results could lead to a better
understanding of the underlying pathophysiology of DBS-related cognitive and
psychiatric side effects in PD. The potential societal benefit is considerable,
since this knowledge may lead to optimization of electrode placement and
contact point selection in STN-DBS. Hence, this can considerably improve the
clinical outcome of this frequently used treatment.
De Boelelaan 1117
Amsterdam 1081HV
NL
De Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
-Having undergone STN-DBS placement for PD six months or longer before MEG registrations;
-Age * 18 years;
-Written informed consent for the study;
-Monopolar stimulation (this restriction was chosen in order to improve inter-individual comparability);
-Pre-operative DTI data available and of sufficient quality. The patient*s nose should be included in at least one pre-operative MRI to allow optimal co-registration with the MEG data;
-Post-operative NPO is available and was performed in the same DBS settings as during the MEG recordings.
Exclusion criteria
-Hoehn and Yahr stage (41) higher than 3, as determined in the DBS ON- (but medication OFF-)state during the visit to the outpatient clinic to establish the optimal DBS-settings, approximately ten days after surgery;
-Anatomical deformities that prevent the subject from undergoing an MEG registration in supine position (i.e. thoracic kyphosis);
-Continuous intrajejunal levodopa or subcutaneous apomorphine infusion in addition to DBS;
-Subjects who cannot read, speak or understand Dutch;
-Dementia according to the Movement Disorder Society criteria for PD with dementia (43). Mental competence is necessary in order to give informed consent for participation in the study and to follow instructions during MEG recordings. Minor cognitive decline post-DBS is not an exclusion criterion, since this is one of the outcome parameters of this study;
-Conditions that will cause excessive MEG artefacts (other than the DBS electrode and stimulator). A list of items that cause MEG signal perturbation is given in the participants information folder, on a poster at the entrance of the MEG system, and in this document (section 11);
-A history of stroke or major vascular lesions on brain MRI;
-A history of major traumatic brain injury;
-Peri-operative intracerebral complications (e.g. bleeding or infection) related to STN-DBS placement inflicting permanent changes;
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL62093.029.17 |