Safety Study of Deep Brain Stimulation to Manage Thalamic Pain Syndrome

This is a pilot clinical study of the therapeutic benefits of ventral capsular/ventral
striatal deep brain stimulation (DBS) as a treatment for 10 patients with medically
refractory thalamic pain syndrome. Patients to be enrolled under this protocol will have
experienced severe pain for more than six months and will be considered medically
refractory. Study subjects may have undergone and failed other surgical procedures or
interventional procedures. Study subjects will have chronic, medically refractory pain of
disabling severity, refractory to treatment attempts with conventional medications. Patients
that are enrolled in the study will have bilateral DBS surgery, with implantation of one
Medtronic 3391 DBS lead on either side of the brain. These leads will then be connected at
first to a single Medtronic PC pulse generator to be implanted in the infraclavicular region
on one side. Once the PC pulse generator is depleted, and the patient has completed the
blinded phase of the study, the PC pulse generator will be replaced for an RC pulse
generator. The RC pulse generator has a battery life of 9 years and is a good option for the
open label phase and for continued stimulation after the study is completed. However, the RC
is not ideal for the blinded phase because patients may be able to tell if they are
receiving active or sham stimulation. For this reason, patients enrolled in this study will
receive, initially, the implant with the PC generator. Patients will have at least 6 months
of stable chronic pain associated with TPS.

Inclusion Criteria:

- Clinical diagnosis of thalamic pain syndrome

- with allodynia or dysesthesia

- with pinprick anesthesia or hypoesthesia on the affected hemibody (anesthesia
dolorosa).

- Six months or more of medically refractory severe pain (see below).

- Pain disability reported by the pain index >30 points at the time of enrollment.

- Average daily pain for the past 30 days reported as >5 on a 0-10 scale

- Failure to respond adequately to at least one antidepressant, one anti-seizure
medication and one oral narcotic.

- MRI done within one year of the first visit showing a lesion that involves the
posterior thalamic region or a lesion in the dorsal or ventral vicinity of the
thalamus (i.e. semi oval white matter or brain stem). The lesion will be
contralateral to the hemibody affected by chronic pain or will involve
cortical-subcortical areas in topography consistent with sensory thalamocortical
connections. This will include patients with infarcts in the territory of the middle
cerebral artery. A more recent MRI may be required if the patient's condition changed
within the previous year.

- Capable of understanding and providing informed consent

- Age ≥ 21 years

- Women of childbearing age must be on regular use of an accepted contraceptive
method(s).

- Previous surgical procedures: Patients with severe and refractory thalamic pain
syndrome may have undergone other interventional or surgical procedures, as an
attempt to alleviate the thalamic pain syndrome. Surgical procedure may include
blocks, spinal cord stimulation, thalamic DBS, posterior limb of the internal capsule
DBS or periaqueductal gray / periventricular gray DBS, cortical stimulation,
peripheral ablative procedures or cerebral ablative procedures. In this study,
patients with previously implanted cortical stimulation systems, or spinal and
peripheral nervous system stimulation systems may be included. However, patients with
previous motor cortex stimulation must have had the cortical stimulation system
before being considered a candidate for this protocol. Removal of the cortical
stimulation system will not be covered under this protocol. Patients with spinal or
peripheral neuromodulation system may be included in the research provided that the
implanted systems are compatible with the all research protocols (including fMRI) to
be performed during the research. Patients with pervious DBS implants will not be
considered candidates.

Exclusion Criteria:

- Not capable of understanding or providing informed consent.

- Aphasia severe enough to limit the consent process or communication between the
investigators and the patient. Patients with mild or recovering aphasia may be
considered candidates at the discretion of the PI.

- Coagulopathy. Patients will be excluded unless assessed and cleared by hematology

- Inability to stop Coumadin or platelet anti-aggregation therapy for surgery and after
surgery. Patients taking these medications will need to discuss the need/risk of
continuing these medications with their physicians and the PI or study personnel may
contact the treating physician(s) as well to discuss the risks of anticoagulation /
antiaggregation therapy discontinuation.

- Uncontrolled hypertension.

- Malignancy with < 5 years life expectancy.

- Major medical co-morbidities: end stage renal failure, heart failure, severe
congestive heart disease, severe respiratory problems, liver failure or other
significant medical co morbidities.

- Major neurological disorder other than the one that led to the TPS.

- MRI (done within one year of the first visit) with abnormalities other than those
associated with the neurological disorder causing TPS.

- Age < 21 years.

- Pregnancy or lack of regular use of contraceptives. Patients who become pregnant
after enrollment may be excluded from the study. Patients who become pregnant prior
to the surgical implantation of the DBS systems will be excluded from the study.

- Previous ablative intracranial surgery for the management of the TPS.

- Previously implanted with deep brain stimulation system.

- Concurrent enrolment in any other trial / study for TPS.

- Implantable hardware not compatible with MRI or with the study.

- Patients may be excluded from enrollment due to a condition that, in the judgment of
the PI, significantly increases risk or reduces significantly the likelihood of
benefit from VC/VS DBS.

- Untreated / uncontrolled (severe at the time of enrolment) depression or other
psychiatric disorder.

- Bipolar disorder, current PTSD, severe personality disorder, active psychosis, Severe
OCD.

- Psychological co-morbidities that indicates higher risk to the patient and / or
higher risk of failure.

- Suicide attempt
- Communication of a plan for suicide, prior to implant, should the study treatment
fail

- Imminent suicide risk