The primary objective is to avoid cognitive and affective side effects and maintain the beneficial motor effects by selective stimulation of the STN motor part. With the Select Stim project we want to improve the classical operation procedure, in…
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
There are two main endpoints to measure the feasibility. First, the patients
burden and outcome. We will interview the patient and ask him to fill in a
standardized questionnaire. Only if the burden is acceptable, we will start
with the main study (average marks for each testing must be above 5 to continue
with a RCT). Thereby the motor symptoms must be significantly less pronounced
with stimulation than pre-operatively.
Secondly, the technical feasibility depends on the possibility to register the
potentials, evoked by motor cortex stimulation in the STN (so-called evoked
potentials). These potentials have to be clearly identifiable in order to
recognize the motor part of the STN. This is necessary as in the final study we
want to compare the results of selective stimulation of the motor part of the
STN with results of the classical procedure.
Secondary outcome
Cognition, and in particular impulsivity, and affect, will be assessed by
neuropsychological testing and a self-report questionnaire, the Positive and
Negative Affect Scale (Watson et al 1988). Neuropsychological testing covers
the main cognitive domains but the study parameters are related to the
performance on tasks in the relevant domain of executive functioning, including
word fluency, the Stroop (Lezak, 2004), a finger precuing task (Adam et al,
2002) and the Iowa Gambling Task (Bechera et al., 1994). (These are not
endpoints of the feasibility trial.)
Advantage of fMRI above TMS or double contrast MRI in the planning of the OR.
Background summary
Parkinson disease (PD) is a common neurodegenerative disorder, characterized by
motor symptoms. Patients are initially treated successfully with drugs (e.g.
levodopa), unfortunately use is limited due to severe side effects. In the
advanced stages of PD neurosurgical treatment is the next therapeutic option.
As a result of dopamine depletion in PD the subthalamic nucleus (STN)
displays a characteristic burst activity. This burst activity results in
dysregulation of the electrical activity of the cortico-basal
ganglia-thalamo-cortical circuitry and is expressed by Parkinsonian symptoms.
That is why the STN is a main target for deep brain stimulation (DBS) in PD.
Long-term follow-up (since 1993) shows long lasting beneficial effects on the
motor function of PD patients.
Despite the beneficial motor effects there are important negative
side-effects of STN DBS. These include both cognitive and affective changes
during stimulation, 40% has one of these side effects. 10% experience
difficulties during their daily functioning due to altered cognition or
personality changes. Presently, the underlying mechanism of these stimulation
induced behavioral changes is not fully understood and therefore adequate
treatment is lacking.
The STN can be divided in three functionally and anatomically
segregated parts: a motor part, a cognitive part and a limbic part. Our
hypothesis is that changes in cognition and behavior during STN DBS are related
to stimulation of the non-motor parts of the STN.
Currently, good candidates are excluded from STN DBS because of the high risk
of behavioral disorders.
Study objective
The primary objective is to avoid cognitive and affective side effects and
maintain the beneficial motor effects by selective stimulation of the STN motor
part. With the Select Stim project we want to improve the classical operation
procedure, in such way that the behavioral side effects will be less present
and the motor symptoms of the disease will be treated. In a later stage, we
want to compare the classical treatment in comparison to this new method. The
outcome we are interested in are the Parkinson symptoms, but also the side
effects of the stimulation on cognitive functioning, mood and behavior. The
main objective of this feasibility study is to measure the patients burden and
to test the technical feasibility.
The feasibility study will answer the following: is targeting of the
subthalamic nucleus, using stimulation of the motor cortex and registration in
the subthalamic nucleus technically achievable? The primary goal is to
determine the technical feasibility and the patient tolerance. If the method is
technical achievable and well tolerated by the patients, we want to give answer
to the main question with a randomized trial.
Study design
The first stage consists of a feasibility study. Three patients will be
enrolled and evaluated. Blinding and randomization is not necessary. Depending
on the results of this minor feasibility study, we will proceed with the second
stage, which is the randomized controlled trial.
Intervention
The intervention is an expansion of the classical STN DBS procedure. The
targeting using the multichannel registration system by stimulation of the
motor cortex and registration of the subthalamic nucleus will be added to the
procedure. For this procedure, it is necessary to place a subdural strip under
the skull.
Study burden and risks
The burden for the patients rests within lengthened operation time and the
pre-operative preparation. The preparation for this study will contain a
functional MRI. The patient needs to lie in the scanner for a prolonged time
(max. 30 min.). And an TMS will be performed to localise the hand area on the
motor cortex, which will take about 60 minutes. This test is not painful. The
operation will be lengthened with one hour per side.
Adverse events related to the implantation of the subdural strip electrodes for
the motor cortex stimulation are described in epilepsy research where these
strips are also used. The most important complications involve bleeding,
infection, transient neurological deficit, intracranial hypertension, seizures.
A large retrospective study (185 patients with epilepsy who had an implantation
of a subdural strip) shows that strip electrode implantation is rarely
associated with complications, e.g. epidural hematoma 1.6%, subdural hematoma
1.1%, brain edema 1.1%, postoperative infection 1.1%, transient aphasia 1.1%,
occurrence of non-habitual seizures 2.7%. Most of these published complications
are in context of prolonged (e.g. several days) monitoring in epilepsy
treatment. We expect the risk of seizures to be lower in Parkinson disease
patients. Moreover, in this study the subdural strips are only used for just an
hour for recording and stimulation of the motor cortex. So, the risk of the
various complications mentioned above will probably be even lower.
The strips will be implanted through the same burr hole through which the five
depth electrodes are implanted like in the classical procedure. Only if this
appears to be impossible during the procedure, a second burr hole will be made.
The risk of this (bleeding and infection) is very low (less than 0.25%).
In the first two patients seizures occurred. The first patient had a seizure
after the surgery, which was countered by the administration of diphantoin. The
second patient had only clonic movements of the hand, which also disappeared
after administration of anti-epileptic drugs. Both patients recovered well.
They are now seizure free and have no additional neurological deficits. To
prevent seizures in the next patient we will load him with diphantoin. The risk
of seizures is very small with the administration of diphantoin.
The most important side effects of diphantoin are nausea, vomiting, obstipation
and anorexia, also dizziness ataxia, nystagmus, speech disturbances, tremor,
apathy, visual disturbances, nervosity, hallucinations and neuropathy. The
adverse effects are mainly reported after long term treatment.
After intravenous administration hypotension can occur and cardiotoxic
reactions, collaps and/ or central depression; incidentally dyskinesias. The
injection site can hurt, show inflammation and necrosis of the skin. The
diphantoin will be loaded in a safe time spam (90min) through a safe
intravenous line by the anesthetist in the srugery room.
Oxfordlaan 10
6229 EV Maastricht
Nederland
Oxfordlaan 10
6229 EV Maastricht
Nederland
Listed location countries
Age
Inclusion criteria
Patients with the clinical findings consistent with idiopathic Parkinson Disease (PD) and who suffer from severe response fluctuations and/or dyskinesias, despite optimal drug treatment, who are candidates for DBS.
Exclusion criteria
Those PD patients suffering from severe psychiatric co-morbidities and cognitive decline, e.g. dementia and psychosis, are excluded from this study. The mini mental state exam (MMSE) score is not allowed to be <24. Other exclusion criteria are the same as for the classical STN DBS operation: significant cerebral atrophy, causative factors of PD, multiple white matter lesions or focal brain anomalies and a Hoehn and Yahr stage of 5 at the best moment of the day.
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 | NL21387.068.08 |