MR Guided Focused Ultrasound for Treatment of Neuropathic Pain

The primary purpose of this study is to assess the safety of MRI-guided focused ultrasound
(MRgFUS) in patients with chronic neuropathic pain whose medicines are not working well. The
device that will be used to create and send ultrasound waves through the skull is called the
ExAblate Transcranial system. The ultrasounds waves will precisely target a small part of the
brain known as the thalamus. Chronic neuropathic pain is a common type of disabling pain that
affects people.

Usually, people with chronic neuropathic pain are treated with medicines to control the pain.
However, these medications may not provide adequate relief of the pain or may be associated
with undesirable side effects. This study intends to investigate the use of a new technology
The ExAblate transcranial system for treating patients that are not responding to medications
and continue to have disabling pain.

The ExAblate Transcranial system will be used to destroy a small cluster of cells that may be
causing the study participant's pain . The ExAblate uses ultrasound to heat a small spot in
the brain. The process of ablation is similar to a magnifying glass that uses light to heat a
small spot on a piece of paper. Ultrasound passes through the skin and skull and into the
brain to focus on a spot the study investigator wants to treat.Once the spot is destroyed, it
cannot grow back.

Inclusion Criteria:

- These include patients with:

1. Severe uncontrolled neuropathic pain due to radiculopathy or radicular injury

2. Spinal Cord Injury

3. Phantom Limb Pain

Patients that have had prior motor cortex stimulation or spinal cord stimulators will be
eligible provided that the hardware has been removed at least six months ago. Detailed
inclusion and exclusion criteria for the study are listed below:

Inclusion criteria:

1. Age greater than 21 and less than 75 years

2. Subjects who are able and willing to give consent and able to attend all study visits,

3. Documented Neuropathic pain for more than 6 months duration, confirmed from clinical
history and examination by a pain specialist or neurologist

4. Failure to respond to any of the usual therapeutic regimens considered to be standard
of care for neuropathic pain. The patient should have failed a trial of at least three
pain medications, including at least one opioid agent

5. Patient should have failed one additional pain intervention such as nerve block,
epidural steroid injection, motor cortex or spinal cord stimulator

6. Subjects should have been on stable dose of analgesic agents for at least a period of
4 weeks

7. Clinical symptoms consistent with persistent, intractable pain that has remained at
average NRS score >5 for 30 days, significant pain related disability (Pain Disability
Index (PDI) score >30) or severe allodynia.

8. Central lateral thalamotomy is feasible based on evaluation of imaging studies

9. Patient able to communicate sensations during the ExAblate TcMRgFUS treatment

10. Two members of the medical team have agreed upon inclusion and exclusion criteria.

Exclusion Criteria:

1. Patient with contra-indications to MRI such as severe claustrophobia and metallic
implants incompatible with MRI.

2. Severe psychiatric disorder such as uncontrolled depression, bipolar disorder, prior
attempt at suicide or suicide ideation in preceding 12 months

3. Life expectancy less than 12 months

4. Anticoagulant or antiplatelet medications as well as underlying coagulopathy

5. Prior or currently implanted thalamic DBS

6. Pregnant ladies or women of childbearing age who are sexually active and not using
contraception

7. Inability to provide informed consent, for example due to underlying cognitive
impairment or aphasia

8. Presence of intracranial mass or an acute intracranial abnormality

9. Subjects with unstable cardiac status such as Unstable angina pectoris, documented
myocardial infarction within 6 months of protocol entry and ejection fraction less
than 40

10. Subjects exhibiting any behavior(s) consistent with ethanol or substance abuse as
defined by the criteria outlined in the DSM-IV as manifested by one (or more) of the
following occurring within a 12 month period:

1. Recurrent substance use resulting in a failure to fulfill major role obligations
at work, school, or home (such as repeated absences or poor work performance
related to substance use; substance-related absences, suspensions, or expulsions
from school; or neglect of children or household).

2. Recurrent substance use in situations in which it is physically hazardous (such
as driving an automobile or operating a machine when impaired by substance use)

3. Recurrent substance-related legal problems (such as arrests for substance related
disorderly conduct)

4. Continued substance use despite having persistent or recurrent social or
interpersonal problems caused or exacerbated by the effects of the substance (for
example, arguments with spouse about consequences of intoxication and physical
fights).

11. Severe hypertension (diastolic BP > 100 on medication or persistently elevated SBP>140
mmHg despite antihypertensive medications)

12. History of immunocompromise including those who are HIV positive.

13. History of CNS disease (this includes but not limited to intracranial hemorrhage,
Traumatic brain injury or thalamic stroke, seizures within the past year, brain
tumors, multiple CVA or CVA within 6 months)

14. Subjects with life-threatening systemic disease that include and not limited to the
following will be excluded from the study participation: HIV, Liver Failure, blood
dyscrasias, etc.

15. Individuals who are not able or willing to tolerate the required prolonged stationary
supine position during treatment (can be up to 4 hrs of total table time.)

16. Are participating or have participated in another clinical trial in the last 30 days

17. Patients receiving a Morphine equivalent dose of greater than 90 mg per day

18. Subjects who have non-neuropathic pain as the major component of their pain
presentation will be excluded from the study.