Mirror Therapy for Phantom Limb Pain

Objective: The aim of this study is to investigate phantom limb pain (PLP), cortical
reorganization and the modulation of PLP by visual input. Mirror therapy (viewing the intact
limb in a mirror so that it appears to be the missing limb) has been shown to reduce PLP.
This reduction demonstrates that vision can play a key role in modulating PLP. The study
proposed here will identify brain regions critical for the success of this therapy using
functional magnetic resonance imaging (fMRI).

Study population: Individuals with unilateral amputation of individual limbs and at least
three episodes of PLP a week. Additionally, we will study amputees without PLP and healthy
control volunteer subjects with no limb amputations.

Design: Amputee subjects with PLP will be scanned using fMRI while they undergo mirror
therapy for PLP. During fMRI scans subjects will see images of hands or feet, move their
limbs or experience tactile stimulation. Mirror therapy requires four weeks to be effective.
Amputee subjects will be scanned prior to starting therapy, two weeks after starting mirror
therapy and again after four weeks of mirror therapy. Mirror therapy sessions will be
conducted daily and subjects will also complete daily questionnaires (Visual Analogue Scale,
or VAS, and Short-Form McGill Pain Questionnaire or SF-MPQ) assessing their level of pain and
number of PLP episodes. Amputees without PLP and one group of healthy control subjects will
go through the same series of functional imaging scans over the same time period as the
amputee subjects, allowing us to identify brain changes that may be associated with repeated
scanning (e.g. due to practice of tasks) rather than resulting from the mirror therapy.
Another group of control subjects will be scanned once to identify particular brain regions
that might be involved in the integration of visual, motor and somatosensory information for
use in the analysis of the amputee subject data.

Outcome measures: Changes in fMRI activation during the course of mirror therapy will be
compared with data on the number of episodes of PLP, the average length of episodes, and the
average intensity of pain assessed using the VAS and SF-MPQ. Analyses will focus on cortical
regions known to be involved in visual, tactile and motor representations (including primary
motor cortex, primary and secondary somatosensory cortex and regions of visual cortex
selectively responsive during the viewing of body parts). Additional brain regions that might
be involved in integrating visual, motor and somatosensory information will be identified in
control subjects. Direct comparisons will be made between cortical regions (e.g.
somatosensory regions) involved in the representation of the amputated limb compared with the
intact limb and between amputee subject data and control subject data.

- INCLUSION CRITERIA:

For amputee subjects with PLP:

- Male or female subjects, 18 to 75 years of age

- Written informed consent and written authorization for use or release of health and
research study information

- Unilateral limb amputation

- Any level of prosthetic experience

- No prior history of vertebral disk disease/condition, sciatica or radiculopathy.

- No evidence of traumatic brain injury (TBI - permanent or temporary impairments of
cognitive, physical and psychosocial functions with an associated diminished or
altered state of consciousness)

- No known neurological disease or brain damage

- No neurological condition that would interfere with participation in the study

- Minimum of 3 phantom limb pain episodes each week

- Degree of pain evaluated by VAS scoring a minimum of 3 cm at time of screening for
entry into study

- Ability to follow study instructions and likely to complete all required visits.

For amputee subjects without PLP:

- Male or female subjects, 18 to 75 years of age

- Written informed consent and written authorization for use or release of health and
research study information

- Unilateral limb amputation

- Any level of prosthetic experience

- No prior history of vertebral disk disease/condition, sciatica or radiculopathy.

- No evidence of traumatic brain injury (TBI - permanent or temporary impairments of
cognitive, physical and psychosocial functions with an associated diminished or
altered state of consciousness)

- No known neurological disease or brain damage

- No neurological condition that would interfere with participation in the study

- No recurring episodes of PLP

- Ability to follow study instructions and likely to complete all required visits.

For healthy control subjects:

- Male or female subjects, 18 to 75 years of age.

- Written informed consent and written authorization for use or release of health and
research study information.

- No prior history of vertebral disk disease/condition, sciatica or radiculopathy.

- Normal neurological examination.

- Ability to follow study instructions and likely to complete all required visits.

EXCLUSION CRITERIA:

For amputee subjects with PLP:

- Age less than 18 or greater than 75 years.

- Multiple limb amputation

- Amputation due to diabetes or vascular claudication

- Pending revision surgeries.

- Presence of embedded metallic shrapnel or other metal not compatible with MRIscanning.

- Presence of traumatic brain injury

- Known uncontrolled systemic disease- known cancer not in remission, known on-going
infection, lupus, kidney disease requiring dialysis, any other systemic disease which
might affect ability to participate in this study to its conclusion

- Concurrent participation in another investigational drug or device study for phantom
limb pain or participation in the 30 days immediately prior to study enrollment.

- Any condition or situation that, in the investigator's opinion, may put the subject at
significant risk, confound the study results, or interfere significantly with the
subject's participation in the study.

- Current Axis I or II diagnosis determined by a neurologist or psychiatrist in the 6
months prior to entry into the study.

- Subjects with lack of effort as determined by the neurologist or physiatrist. Subjects
will be screened for effort using the Test of Memory Malingering (TOMM) first in order
to exclude those with blatant exaggeration or malingering.

- Positive pregnancy test at the time of scanning (within 24 hours prior to the
scheduled MRI scan, female subjects of child-bearing age will be given a pregnancy
test)

For amputee subjects without PLP:

- Age less than 18 or greater than 75 years.

- Multiple limb amputation.

- Amputation due to diabetes or vascular claudication

- Pending revision surgeries.

- Presence of embedded metallic shrapnel or other metal not compatible with MRI
scanning.

- Presence of traumatic brain injury

- Known uncontrolled systemic disease- known cancer not in remission, known on-going
infection, lupus, kidney disease requiring dialysis, any other systemic disease which
might affect ability to participate in this study to its conclusion

- Concurrent participation in another investigational drug or device study for phantom
limb pain or participation in the 30 days immediately prior to study enrollment.

- Any condition or situation that, in the investigator's opinion, may put the subject at
significant risk, confound the study results, or interfere significantly with the
subject's participation in the study.

- Current Axis I or II diagnosis determined by a neurologist or psychiatrist in the 6
months prior to entry into the study.

- Subjects with lack of effort as determined by the neurologist or physiatrist. Subjects
will be screened for effort using the Test of Memory Malingering (TOMM) first in order
to exclude those with blatant exaggeration or malingering.

- Positive pregnancy test at the time of scanning (within 24 hours prior to the
scheduled MRI scan, female subjects of child-bearing age will be given a pregnancy
test)

For healthy control subjects:

- Age less than 18 or greater than 75 years

- Presence of an amputation

- Presence of embedded metallic shrapnel or other metal not compatible with MRI
scanning.

- Presence of traumatic brain injury

- Known uncontrolled systemic disease- known cancer not in remission, known on-going
infection, lupus, kidney disease requiring dialysis, any other systemic disease which
might affect ability to participate in this study to its conclusion

- Any condition or situation that, in the investigator's opinion, may put the subject at
significant risk, confound the study results, or interfere significantly with the
subject's participation in the study

- Current Axis I or II diagnosis determined by a neurologist or psychiatrist in the 6
months prior to entry into the study

- Positive pregnancy test at the time of scanning (within 24 hours prior to the
scheduled MRI scan, female subjects of child-bearing age will be given a pregnancy
test)