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Phantom limb pain is
very common after limb amputation and is often difficult to treat.
The motor cortex stimulation is a valid treatment for deafferentation
pain that does not respond to conventional pain treatment, with
relief for 50% to 70% of patients. This treatment is invasive as it
uses implanted epidural electrodes. Cortical stimulation can be
performed noninvasively by repetitive transcranial magnetic
stimulation (rTMS). The stimulation of the hemisphere that isn't
involved in phantom limb (unaffected hemisphere), remains unexplored.
We report a case of phantom limb pain treated with 1 Hz rTMS
stimulation over motor cortex in unaffected hemisphere. This
stimulation produces a relevant clinical improvement of phantom limb
pain; however, further studies are necessary to determine the
efficacy of the method and the stimulation parameters.
1. Introduction
Phantom limb pain
(PLP) is very common after limb amputation and has a reported
incidence of up to 87% of amputees [1]. This type of pain can be
difficult to treat and usually responds poorly to conventional pain
treatments [2–4]. Conversely, the electrical stimulation of the
primary motor cortex (M1) has proved to be an effective treatment for
intractable deafferentation pain. This treatment started in 1990, and
many patients have been treated up to now. The patients who have been
operated on were suffering from poststroke pain (59%), trigeminal
neuropathic pain, brachial plexus injury, spinal cord injury,
peripheral nerve injury, and phantom limb pain [5]. This treatment
consists in chronic motor cortex stimulation (MCS) through implanted
epidural electrodes. It results invasive and outcome varies from
patient to patient [6, 7]. Otherwise cortical stimulation can be
performed non-invasively by transcranial magnetic stimulation (TMS).
A number of studies have shown that a single session of repetitive
transcranial magnetic stimulation (rTMS) can relieve pain transiently
in some patients with chronic neuropathic pain [8–10]. Other
studies have shown that the duration of pain relief can be extended
by repeated application of rTMS every day for five days in patient
with trigeminal neuralgia and poststroke pain syndrome [6] or for ten
days in patients with fibromyalgia [11]. In contrast, one study
failed to see any long-term therapeutic effect of three weeks daily
parietal cortex rTMS in two patients with phantom limb pain [12]. The
majority of studies apply high frequencies (>1) with pulses below
motor threshold on motor cortical area corresponding to the hand of
the painful side. The reason for this is twofold: epidural
stimulation usually employs pulses below motor threshold at ~40 Hz.
and a study shows that the applications of rTMS at high frequency is
more effective than applications of rTMS at low frequency (≤1) in
this area of stimulation [8]. However, the effect of stimulation in
unaffected hemisphere for phantom limb pain remains unexplored. In
other cases, like neglect or recovery in stroke, stimulation with low
frequency rTMS in unaffected hemisphere have shown therapeutic
properties [13, 14]. We report a case of phantom pain limb treated
with 1 Hz stimulation over motor cortex in unaffected hemisphere.
2. Case Study
A 36-yr-old,
right-handed man, who had had a motorbike accident ten years ago, had
total surgical amputation of the left arm. At the time of his arrival
to our institute, he had perception of phantom limb and was
experiencing severe phantom limb pain. This perception and pain have
existed immediately after the amputation. The perception of phantom
limb was always in the same position near the chest with the hand
partially closed near the shoulder. The patient experienced pain like
paresthesia, dysaesthesia and burning sensation especially in phantom
thumb, index and medium, and in the total phantom limb too. The pain
was present every day, always in wakefulness but not in sleep. Such
pain persisted during the day and sometime became very intense for
some seconds. In the past, the patient tried antiepileptic drugs,
tricyclic and SSRI antidepressant, anti-inflammatory-analgesics, and
opioids in order to relieve the pain. At the time of his arrival to
our institute, he was having the best therapy that gave a partial
relief to the pain. The therapy consisted in methadone 30 mg/day
and pregabalin 300 mg/day. Neurological examination showed miosis
and light ptosis in left eye, like Bernard-Horner syndrome which has
existed immediately after the amputation. The examination also showed
tactile hypoesthesia in the surgical scar, while the tactile
stimulation of the area near the scar increased the pain in the
phantom limb. The tactile stimulation of the left side of the face
increased the pain in the phantom limb too. Chest MRI and CT with
contrast excluded a peripheral component of pain due to a concomitant
lesion of the inferior brachial plexus. The patient gave the written
informed consent. At the baseline, at the end of every week, for
three weeks during treatment and at the end of every week for three
weeks after treatment, the following tests were administered:
Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating scale
for Anxiety (HAM-A), Mania Rating Scale (MRS), CORSI TEST, Phonemic
Verbal Fluency, and Visual Analogue Scale (VAS) for pain-0 (no pain)
and 10 (maximal pain). The percentage of pain level modification was
calculated from the VAS score by the following equation (post.rTMS –
pre.rTMS pain scores) × 100/(pre.rTMS pain scores). Figure 1 below
shows the reduction in percentage of pain in time. Clinical Global
Impression-Improvement scale (CGI-I) was evaluated at the end of the
third week of treatment. rTMS sessions were conducted in a laboratory
staffed by physicians certified in basic life support and trained in
the prompt recognition and treatment of seizures and other medical
emergencies. Repetitive TMS was administered using a MAGSTIM rapid
magnetic stimulator (Magstim Company, Ltd., Whitland, U.K.). We used
a 70-mm figure eight-shaped coil. Patient sat in a reclining chair
with a headrest for stabilization of the head and wore protective
earplugs. Resting motor threshold (RMT) was defined as the intensity
required eliciting at least five MEPs of 50 μV in peak-to-peak
amplitude with 10 consecutive stimulations, when the coil was placed
over the optimal position to activate the abductor pollicis brevis
muscle in right hand based on electromyographic recording [15].
During treatment, the following were applied for 15 minutes, thirty
20-second trains at 1 Hz at 80% of RMT with a 10 seconds intertrain
interval (a total of 600 stimuli per session were applied over the
left motor cortex), these parameters are now widely considered safe
[16]. A full course comprised fifteen daily sessions administered on
weekdays, beginning on Monday. At all times, the coil was held
tangentially to the scalp, with the handle pointing back and away
from the midline at 45°. During every session of stimulation the
patient had the sensation that the phantom limb went away from the
shoulder towards mid-line in the direction of the pelvis, and the
intensity of phantom limb pain reduced. The patient experienced no
adverse event during or after rTMS application. At the end of the
third week of treatment, the pain was reduced about 33.3% (see Figure
1), in fact VAS changed from 6 (pretreatment) to 4 (posttreatment),
with CGI-I = 2 (much improved). In three weeks after treatment the
percentage reduction of pain was reduced to 25% in the first week
after the end of treatment and remained stable at about 16.6% in the
second and in the third week after the end of treatment (Figure 1).
During the three weeks of treatment and during the three weeks after
treatment, Ham-D, Ham-A, and MRS all remained stable at ≤6. Also,
score of the CORSI TEST remained stable at 5 and the score of the
Phonemic Verbal Fluency remained stable at 17.6 and so these tests
did not show cognitive impairment or improvement. RMT of unaffected
hemisphere increased during treatment, in fact at baseline its value
was 84% of Maximum Output of the Stimulator, after the first week of
treatment, its value was 86% of Maximum Output of the Stimulator, and
at the end of the second and third week of treatment its value was
stable at 88% of Maximum Output of the Stimulator.