To explore the efficacy of central thalamic DBS in restoring consciousness in MCS patients. Hypothesis: Central thalamic DBS improves the level of consciousness in MCS patients.
ID
Source
Brief title
Condition
- Other condition
- Structural brain disorders
Synonym
Health condition
chronische bewustzijnsstoornissen
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome of this study is the change on the CRS-R and the number of
patients that emerges from MCS.
Secondary outcome
Secondary endpoints are changes on a subset of additional behavioral scales for
patients recovering from coma (PALOC-S, DRS), the effects of DBS treatment on
the perceived change of consciousness and its appreciation by family members,
and the quality of life and health in family members as measured by the
WHOQOL-BREF. Moreover, neurophysiological parameters will be compared between
the preoperative and postoperatieve state using MEG.
Background summary
The unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS)
are disorders of consciousness that are among the most dramatic conditions in
medicine. There is currently no treatment for improvement or restoration of the
level of consciousness. It is hypothesized that chronic hypo-activation of
central thalamic outflow tracts to the cortex is the main cause of disorders of
consciousness. While UWS patients only have periods of wakefulness, MCS
patients show partial preservation of conscious awareness. Moreover, recent
neuroimaging studies in MCS patients show sparing of cortical connectivity,
which provides the necessary substrate to harness the effects of explorative
interventions to restore consciousness. Since the 1960s, deep brain stimulation
(DBS) of the central thalamus has been applied in small, uncontrolled patient
series, mostly consisting of UWS patients. Behavioral responsiveness was
reported in many cases, especially in MCS patients, but methodological
weaknesses, such as inclusion within the known time-frame of natural recovery
makes it impossible to judge whether the improvements were due to the DBS
itself. A clinical DBS trial with a series of persistent MCS patients has not
been performed, but is much awaited by the international community.
Study objective
To explore the efficacy of central thalamic DBS in restoring consciousness in
MCS patients.
Hypothesis: Central thalamic DBS improves the level of consciousness in MCS
patients.
Study design
A prospective pilot study.
Intervention
DBS electrodes will be implanted bilaterally in the central thalamus and
connected to a pulse generator that is placed under the skin of the chest.
Study burden and risks
There is currently no evidence-based treatment for improvement or restoration
of consciousness in patients suffering from persistent MCS. A large group of
(relatively young) patients ends up in nursing homes without perspective. DBS
is accepted as a safe, adjustable and reversible neurosurgical technique to
modulate brain functioning, and its application in various neurologic and
neuropsychiatric disorders is steadily expanding. Participation in the
RECONNECT pilot study requires a short hospital admission, DBS surgery, and
serial follow-up with four behavioral assessments. Also, two non-invasive
MEG-scans will be made (in the VUmc). Despite the burden of the RECONNECT pilot
study, it provides an opportunity to restore consciousness and perhaps some of
the decision-making capacity of participating patients. The RECONNECT study is
directed to improve care for patients with disorders of consciousness and will
contribute to further development of scientific foundations of electrical
stimulation of the brain network that regulates consciousness. Therefore, it
might benefit a much larger group of patients with severe brain damage and
(chronic) disorders of consciousness. Finally, the results of this pilot-study
may define a rationale for further research and contribute to the determination
of criteria for selection of patients eligible for DBS. If results of this
pilot-study are positive, and the analysis shows that DBS has a significant
impact on both arousal and behavioral awareness, a larger randomized,
double-blind, clinical cross-over study will be proposed.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
• Age 18-65 years
• Diagnosis of MCS according to CRS-R
• The patient is in persistent MCS, i.e. at least 24 months post-injury
• MCS is caused by non-progressive traumatic brain injury (TBI)
• MCS is treatment-refractory, defined as:
- not accompanied by concomitant hydrocephalus
or
- accompanied by concomitant hydrocephalus that has been adequately treated by
permanent cerebrospinal fluid shunting for at least six months with no evidence
of improvement in neurobehavioral function in the last two months prior to
enrolment
and
- previous failure of emergence from MCS by treatment with amantadine, levodopa
and zolpidem
• Independent ventilation
• Stable physical condition
• Written informed consent by primary family caregivers
Exclusion criteria
• Expectation that patients will not be able to meaningfully interact with the
outside world even when consciousness is restored, defined as:
- evidence of significant lesions involving cortical language areas (Wernicke's
and/or Broca's - area) or brainstem on MRI
or
- quadriplegia due to spinal cord injury, brainstem injury, or bilateral loss
of motor cortex on MRI
• Premorbid mental retardation
• MRI-incompatible cardiac pacemaker/defibrillator
• Intractable seizure disorders (status epilepticus)
• Presence of untreated endocrine disturbances (i.e., hyper- or hypothyroidism)
or other biochemical disturbances
• Medical contraindications for DBS or general anesthesia, and comorbid
conditions, including:
- non-closed skull due to previous decompressive hemicraniectomy without proper
cranioplasty
- anatomical barriers for electrode placement on MRI
- local, systemic, acute, or chronic infectious illness
- severe collagen vascular disorder/bleeding disorders
- severe chronic pulmonary disease
- life-threatening cardiac arrhythmias
- kidney failure or other major organ systems failures
- other active neurologic diseases/processes (i.e., multiple sclerosis,
Parkinson*s disease, Alzheimer*s disease)
- neoplasm with life expectancy <5 years
Design
Recruitment
Medical products/devices used
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 | NL58841.018.16 |