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case-report2015
PMJ0010.1177/0269216315574260Palliative MedicineNizard et al.
Case Report
Palliative Medicine
Abstract
Background: Non-drug treatments should be systematically associated to the medical analgesic treatment during the terminal phase
of cancer.
Cases presentation: Patient 1, a 23-year-old woman, presented an adenocarcinoma of the rectum, with liver and lung metastases.
Pain was initially treated by oral morphine and a combination of pregabalin and amitriptyline. Ketamine and intrathecal administration
of morphine were both ineffective. Patient 2, a 69-year-old woman, presented a cutaneous T-cell lymphoma. She was admitted to
the palliative care unit with mixed pain related to cutaneous lymphomatous infiltration. World Health Organization (WHO) step 3
analgesics had not been tolerated.
Cases management: Both patients received five consecutive 20-min sessions of repetitive transcranial magnetic stimulation to the
right motor cortex.
Cases outcome: Patient 1 experienced a marked improvement of her pain over the days following the first repetitive transcranial
magnetic stimulation session. Medical treatment was able to be rapidly decreased by about 50%, which restored an almost normal
level of consciousness and lucidity. Patient 2s pain was also markedly decreased over the days following these five consecutive
sessions, and repetitive transcranial magnetic stimulation also appeared to have had a beneficial effect on the patients anxiety
and mood.
Conclusion: In the context of palliative care of cancer patients experiencing refractory pain that is difficult to control by the usual
treatments, motor cortex repetitive transcranial magnetic stimulation, due to its noninvasive nature, can be used as an adjuvant
therapy to improve various components of pain, including the emotional components. By reducing the doses of analgesics, repetitive
transcranial magnetic stimulation decreases the severity of their adverse effects and improves the patients quality of life.
Keywords
Refractory pain, cancer pain, quality of life, repetitive transcranial magnetic stimulation, rTMS
Background
Cancer pain may correspond to nociceptive pain, generally corresponded to nociceptive pain, due to compression by
relieved by the administration of opioid analgesics, neuro- the tumour, and partly to possible neuropathic pain,1 as a
pathic pain, requiring the use of specific medications such consequence of surgery and radiotherapy (with a DN4
as anticonvulsants or antidepressants, and often mixed score, a screening instrument used to measure neuropathic
pain. Pain can become difficult to control at the terminal pain,2 of 7/10.). This pain was initially treated by oral mor-
phase of cancer due to the mixed nature of the pain and the phine and a combination of pregabalin and amitriptyline.
need to administer high-dose drug combinations, often The patient continued to experience pain despite this treat-
accompanied by drowsiness, which contributes to deterio- ment with a numerical rating scale (NRS) varying between
ration of the quality of the end of life. Non-drug treat- 8 and 10/10. She also suffered from drowsiness and intel-
ments, especially physical and psycho-corporal therapy, lectual slowing that confined her to bed.
should be systematically associated. We report two clinical
cases in which five sessions of repeated transcranial mag- Case management
netic stimulation induced marked relief of the patients
pain and allowed a considerable reduction of their analge- Patient 1 was admitted to the Palliative Care Unit. Initiation
sic drug treatment. To our knowledge, no study has been of N-methyl d-aspartate (NMDA) receptor antagonist (ket-
previously published about repetitive transcranial mag- amine) treatment failed to decrease pain or the doses of
netic stimulation (rTMS) on the context of palliative care. major opioids. Intrathecal administration of morphine was
also ineffective. Introduction of midazolam was minimally
effective and accentuated the patients drowsiness. The
Case report 1 Medication Quantification Scale (MQS) score (used to
quantify analgesic and co-analgesic consumption in chronic
Case presentation pain patients according to drug class, and daily therapeutic
A woman in her early 20s presented an adenocarcinoma of dose)3 was then 126. In view of the patients limited life
the rectum, treated by radiotherapy and abdominopelvic expectancy (less than 3months), the neurosurgeon con-
resection, followed by chemotherapy. She presented local tacted did not propose any specific treatment (neither an
disease progression despite this treatment, with the discov- invasive neurostimulation, nor a destructive procedure).
ery of peritoneal carcinomatosis with liver and lung metas- A therapeutic trial of motor cortex stimulation by
tases. The patients health status gradually deteriorated rTMS was proposed, as we had already obtained good
with increasing abdominal and pelvic pain, which partly results in two cases of refractory pelvic and perineal pain.4
Figure 1. Course of the numerical rating scale (NRS) of pain (solid line) and treatment (Medication Quantification Scale (MQS))
(dotted line) between January 20 and March 16 (a: patient 1) and between February 25 and May 5 (b: patient 2). (a) Evolution of the
NRS and MQS in Patient 1. For greater simplicity, MQS was calculated with a decimal (12.6 instead of 126 on January 20). Sessions
performed on 31/1, 3/2, 6/2, 7/2 and 8/2. (*Start of treatment with midazolam; **Discontinuation of treatment with midazolam;
***Wedding; ****Discharge from the palliative care unit; 3/3: Return to the palliative care unit; 12/3: Onset of terminal phase;
*****Death). (b) Evolution of the NRS in patient 2. Initial MQS score of 12 was relatively low in this second case, and decreased to
4 after rTMS. (*Admission in palliative care unit; **Admission in rest house; ***Death.)
rTMS: repetitive transcranial magnetic stimulation.
in the context of multidisciplinary management provided the mechanisms of action of invasive and noninvasive
by a palliative care unit, appeared to be a potentially useful motor cortex stimulation.7
approach, with a favourable benefit/risk balance. The analgesic efficacy of high frequency (>5Hz)
rTMS has been shown to be effective on both chronic rTMS of the motor cortex on neuropathic pain has now
pain and depression. It is generally associated with been clearly established, with a level of evidence of A8
excellent safety and the rare adverse effects are usually (several convincing class I and II randomized controlled
only minor, and mainly consist of transient headache.8 trials), while the level of evidence remains B/C for non-
The rTMS target generally used to treat depression is the cancer/non-neuropathic pain (complex regional pain syn-
dorsolateral prefrontal cortex, when the target for the drome (CRPS), fibromyalgia, etc.).
treatment of chronic pain is the precentral motor cortex, It has also been regularly observed that even in the case
rather than somatosensory cortical areas. The relevance of bilateral or midline pain, as in the present cases, stimu-
of this target has been confirmed by many studies that lation on only one side could be sufficient.8 A concomitant
have provided convincing evidence for the efficacy and improvement of pain and depression, corresponding to the
affective component of pain, has already been observed in which can lead to a marked improvement in the patients
chronic pain patients treated by motor cortex stimulation,8 quality of life. We are currently conducting a prospective
probably due to functional interactions between the motor open-label study to support the proof of concept and feasi-
cortex and the cingulate, orbitofrontal and prefrontal corti- bility of rTMS in this specific setting, before envisaging a
ces involved in the emotional component of pain. randomized controlled trial comparing active stimulation
This combined effect could be particularly useful in the and sham stimulation.
context of the end of life. In the present cases, rTMS ses-
sions over 1week allowed a significant pain improvement Acknowledgements
and/or reduction of analgesics, allowing the patient to We confirm that Ethical Committee approval was sought and
recover a sufficient level of consciousness, lucidity and that guidelines on patient consent have been met. Both Patient 1
motivation to complete a complex sociofamilial project. and 2 gave their permission for their cases to be written for
As this study was based on only two open-label cases publication.
with no comparison with the sham technique, it is obvi-
ously impossible to draw any conclusions on the efficacy of Declaration of conflicting interests
rTMS in this indication (the effect of rTMS may consist of The authors have no conflicts of interest to declare.
a placebo effect), or to define its potential role, in the pallia-
tive setting, in patients with refractory pain. However, due Funding
to its potentially favourable benefit/risk balance, this tech-
nique appears to be a promising adjuvant therapy in selected This research received no specific grant from any funding agency
in the public, commercial or not-for-profit sectors.
patients, in which short-lasting pain relief is required.
Several potential obstacles, more specific to this popu-
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