Targeting Lower Limb, Upper Limb, and Face Representation in the Primary Motor Cortex for the Practice of Neuronavigated Transcranial Magnetic Stimulation.

OBJECTIVE: The primary motor cortex (M1) is a usual target for therapeutic application of repetitive transcranial magnetic stimulation (rTMS), especially the region of hand motor representation. However, other M1 regions can be considered as potential rTMS targets, such as the region of lower limb or face representation. In this study, we assessed the localization of all these regions on magnetic resonance imaging (MRI) with the aim of defining three standardized M1 targets for the practice of neuronavigated rTMS. MATERIALS AND METHODS: A pointing task of these targets was performed by three rTMS experts on 44 healthy brain MRI data to assess interrater reliability (including the calculation of intraclass correlation coefficients [ICCs] and coefficients of variation [CoVs] and the construction of Bland-Altman plots). In addition, two "standard" brain MRI data were randomly interspersed with the other MRI data to assess intrarater reliability. A barycenter was calculated for each target (with x-y-z coordinates provided in normalized brain coordinate systems), in addition to the geodesic distance between the scalp projection of the barycenters of these different targets. RESULTS: Intrarater and interrater agreement was good, according to ICCs, CoVs, or Bland-Altman plots, although interrater variability was greater for anteroposterior (y) and craniocaudal (z) coordinates, especially for the face target. The scalp projection of the barycenters between the different cortical targets ranged from 32.4 to 35.5 mm for either the lower-limb-to-upper-limb target distance or the upper-limb-to-face target distance. CONCLUSIONS: This work clearly delineates three different targets for the application of motor cortex rTMS that correspond to lower limb, upper limb, and face motor representations. These three targets are sufficiently spaced to consider that their stimulation can act on distinct neural networks.

Bicentre, randomized, parallel-arm, sham-controlled trial of transcranial direct-current stimulation (tDCS) in the treatment of palliative care patients with refractory cancer pain.

BACKGROUND: Pain is a common symptom in palliative care cancer patients and is often insufficiently relieved. In recent years, transcranial direct-current stimulation (tDCS) of the motor cortex has been shown to be effective to treat chronic pain, essentially neuropathic pain. We propose to test the efficacy of tDCS in patients experiencing cancer pain in the palliative care setting. METHOD/DESIGN: This article describes the protocol of a bicentre, randomized, parallel-arm, sham-controlled clinical trial evaluating tDCS in the treatment of palliative care patients with refractory cancer pain. Seventy patients between the ages of 18 and 80 years experiencing refractory pain with a pain score of 4/10 on a numerical rating scale (NRS) ranging from 0 to 10 will be enrolled in this trial. The main exclusion criteria are patients unable to fill in the various rating scales and life expectancy less than 3 weeks. Treatment consists of 5 consecutive tDCS sessions targeting the motor cortex (one daily session for 5 days) on the contralateral side to the pain. After randomization (1:1 ratio), 35 patients will receive active stimulation and 35 patients will receive sham stimulation. The primary endpoint is the NRS score and the primary objective is a significant improvement of this score between the baseline score recorded between D-3 and D-1 and the score recorded 4 days after stopping treatment (D8). The secondary objectives are to evaluate whether this improvement is maintained 16 days after stopping treatment (D21) and whether the following scores are improved on D14 and D21: Brief Pain Inventory, Edmonton Symptom Assessment System, Hospital Anxiety and Depression scale, State-Trait Anxiety Inventory and Medication Quantification Scale. DISCUSSION: Positive results of this trial would indicate that tDCS can improve pain and quality of life of cancer patients in the palliative care setting. Reduction of analgesic consumption and improvement of activities of daily living should allow many patients to return home with a decreased workload for caregivers.

Efficacy of Occipital Nerve Stimulation to Treat Refractory Occipital Headaches: A Single-Institution Study of 60 Patients.

BACKGROUND: Occipital nerve stimulation (ONS) is shown to be effective in treating various forms of headache. Most studies describe the treatment of occipital neuralgia (ON), but in many patients, the clinical description could also correspond to cervicogenic headache (CGH) or occipital migraine (OM). These different entities (ON, CGH, and OM) may be grouped together under the term occipital headaches. OBJECTIVE: To assess the efficacy of ONS to treat occipital headaches in a large series of patients with a long-term follow-up. MATERIALS AND METHODS: We performed a retrospective review of data on 60 patients with intractable occipital headaches treated with occipital nerve stimulation (ONS), who were referred to our center between October 2008 and October 2014. Details of pain evaluation, location, duration, cause and previous treatment were analyzed. Evaluations included the visual analog scale (VAS), the number of headache days per month (NHD), and the Medication Quantification Scale (MQS). Trials with transcutaneous electrical nerve stimulation (TENS-ONS) were performed and served as a guide for surgery indication (see Patients and Method section). RESULTS: After one year of ONS, mean VAS had decreased from 8.4/10 to 2.8/10 (72.2% reduction [p < 0.001]), and 76% of patients had at least a 50% decrease in mean VAS score. The mean MQS score decreased from 18 to 8.8, corresponding to a reduction of pain medication by an average of 50%. Adverse events concerned 12 patients (20%). Six patients presented with electrode displacement or fracture (10%) and six patients presented with cases of infection (10%) associated with the pulse generator. CONCLUSIONS: The results of this large series confirm that ONS is an effective treatment option for patients with intractable occipital headaches, but the frequency of complications remains quite high and must be taken into account in the surgical decision.

Interest of repetitive transcranial magnetic stimulation of the motor cortex in the management of refractory cancer pain in palliative care: Two case reports.

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 2's 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 patient's 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 patient's quality of life.

Benefits of repetitive transcranial magnetic stimulation (rTMS) for spastic subjects: clinical, functional, and biomechanical parameters for lower limb and walking in five hemiparetic patients.

Introduction. Spasticity is a disabling symptom resulting from reorganization of spinal reflexes no longer inhibited by supraspinal control. Several studies have demonstrated interest in repetitive transcranial magnetic stimulation in spastic patients. We conducted a prospective, randomized, double-blind crossover study on five spastic hemiparetic patients to determine whether this type of stimulation of the premotor cortex can provide a clinical benefit. Material and Methods. Two stimulation frequencies (1 Hz and 10 Hz) were tested versus placebo. Patients were assessed clinically, by quantitative analysis of walking and measurement of neuromechanical parameters (H and T reflexes, musculoarticular stiffness of the ankle). Results. No change was observed after placebo and 10 Hz protocols. Clinical parameters were not significantly modified after 1 Hz stimulation, apart from a tendency towards improved recruitment of antagonist muscles on the Fügl-Meyer scale. Only cadence and recurvatum were significantly modified on quantitative analysis of walking. Neuromechanical parameters were modified with significant decreases in H max⁡ /M max⁡ and T/M max⁡ ratios and stiffness indices 9 days or 31 days after initiation of TMS. Conclusion. This preliminary study supports the efficacy of low-frequency TMS to reduce reflex excitability and stiffness of ankle plantar flexors, while clinical signs of spasticity were not significantly modified.

Effects of Combining Music Therapy, Light Therapy, and Chromotherapy in the Treatment of Chronic Pain Patients: A Pilot Study.

Background: It is currently considered that around 30% of chronic pain patients are totally refractory to medical treatment. Among patients who remain responsive to medical treatment, it is estimated that between 20% and 50% are likely to discontinue treatment due to severe side effects. Given these therapeutic difficulties, a significant number of patients turn to complementary therapies. Objective: The LineQuartz® is a medical device that combines 3 complementary therapies, namely, music therapy, light therapy, and chromotherapy. We propose to evaluate its effectiveness in chronic pain patients. Methods: Between October 2021 and October 2022, 44 patients aged between 23 and 85 years (mean: 55.4 years) were included in a prospective study. All patients had background pain intensity greater than 4/10 on the Numerical Pain Scale (NS). Treatment consisted of 4 half-hour sessions, divided into one session per week for 3 weeks (21 days). Patients were assessed by the Brief Pain Inventory (BPI) and the Hospital Anxiety and Depression scale (HAD) the day before starting treatment (Day 0) and the day after the end of treatment (Day 22). Results: Apart from the BPI item, "relationship with others," all items improved significantly (p < 0.050). Background pain intensity (NS) and frequency of painful attacks improved very significantly (p < 0.001). The HAD anxiety subscore was also significantly improved (p < 0.001). Discussion. This open pilot study supports the idea that LineQuartz® has a place among complementary therapies dedicated to the treatment of chronic pain. However, these results need to be confirmed by a controlled study.

Combination of anodal tDCS of the cerebellum with a goal-oriented motor training to treat cervical dystonia: a pilot case series.

Background: Transcranial Direct Current Stimulation (tDCS) of the cerebellum shows promise for the treatment of dystonia. Specific motor rehabilitation programs have also been developed in this context. However, the combination of these two approaches has not yet been evaluated to determine their therapeutic potential. Methods: We report a series of 5 patients with cervical dystonia (CD) poorly controlled by botulinum toxin injections. They were initially treated by a protocol of repeated daily sessions (for 3 or 5 days) of cerebellar anodal tDCS (cer-atDCS) applied alone. In a second time, additional protocols of cer-atDCS were performed in combination with a program of goal-oriented motor training exercises (Mot-Training), specifically developed for the treatment of CD. The clinical impact of the procedures was assessed on the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Results: Compared to baseline, the maximum percentage of TWSTRS total score improvement was 37% on average after cer-atDCS performed alone (p = 0.147, not significant) and 53% on average after cer-atDCS combined with Mot-Training (p = 0.014, significant). The TWSTRS pain and functional handicap subscores also improved after the combined protocol. A score of (+3) to (+5) was rated on the TWSTRS response scale after cer-atDCS performed alone or the combined protocol, corresponding to a moderate to striking improvement on dystonia and pain. This improvement lasted longer after the combined protocol than after cer-atDCS alone (3.4 vs. 1.4 months on average, p = 0.011). Conclusion: The combination of cer-atDCS with Mot-Training produced a greater and more prolonged improvement than the application of cer-atDCS alone. Such a combined therapeutic procedure is easy to perform and opens important perspectives in the long-term treatment of CD. These results remain to be confirmed by a randomized sham-controlled trial on a larger sample.

Motor cortex stimulation in refractory pelvic and perineal pain: report of two successful cases.

AIMS: In some patients, with refractory chronic pelvic and perineal pain, pain and quality of life are barely alleviated despite optimal medical treatment, infiltrations and surgical release of the pudendal nerve. The management of these patients is complex, especially after failure of neuromodulation techniques (spinal cord stimulation. S3 nerve root stimulation and direct stimulation of the pudendal nerve). We report the first two cases illustrating the value of motor cortex stimulation (MCS), in this new indication. METHODS: The history, decision-making process, intraoperative findings and results of this technique are presented. The perineal cortical area was identified by intraoperative motor evoked potentials in the external anal sphincter, confirming its location in the primary motor cortex between the inferior and superior limb positions. As predictive value of repetitive transcranial magnetic stimulation (rTMS) in the identification of responders to MCS for pain is now established, we performed pre-operative rTMS sessions for both patients. RESULTS: The first patient was a 74-years-old woman who reported an 11-year history of left lateral perineal pain. The second patient was a 45-year-old woman who reported a 4-year history of perineal pain following hysterectomy with ovariectomy. After respectively 40 months and 19 months of follow up, both patients reported an improvement of pain ranging from 40 to 50%. Time to onset of pain on sitting was markedly improved from a few minutes to 90 minutes, and largely contributing to improvement of activities of daily living and of quality of life. CONCLUSION: These two first cases suggest that motor cortex stimulation constitutes a new treatment for refractory pelvic and perineal pain, and should be considered after failure of conventional neuromodulation techniques, especially spinal cord stimulation.

Deep brain stimulation in multiple sclerosis-associated tremor. A large, retrospective, longitudinal open label study, with long-term follow-up.

BACKGROUND: Tremor affects up to 25%-58% in multiple sclerosis (MS) population. Deep-brain stimulation (DBS) of the ventral-intermediate nucleus (VIM) of the thalamus is considered as a potential option following medical treatments. Long term DBS efficacy is not well known in these patients with a poor outcome mostly related to disease progression. OBJECTIVE: To report a large and retrospective study of thalamic DBS in MS tremor. METHODS: We conducted a large and retrospective study of patients with MS disabling and pharmacologically resistant upper limb tremor, who underwent thalamic DBS procedure from January 1992 to January 2015 in University Hospital of Henri Mondor, France. Demographic data, clinical assessment and activity daily living were collected. A three-month and twelve-month post-operative assessment with clinical and functional rating scales have been achieved, as well as long term follow-up for most patients. RESULTS: One hundred and four patients underwent DBS procedure. There were 71 female (68%) and 33 male (32%). At three-month post-operative assessment, 64% patients were improved clinically and functionally. Among these, 93% of patients kept a good efficacy at one-year post-operative assessment. Mean duration of follow-up for these patients was 6 years. CONCLUSION: We described a long-term sustained clinical and functional improvement in this large and retrospective report of thalamic DBS. This neuromodulation approach could be a therapeutic option for all severe upper extremity refractory tremor in MS patients.

Treatment of cognitive and mood disorders secondary to traumatic brain injury by the association of bilateral occipital nerve stimulation and a combined protocol of multisite repetitive transcranial magnetic stimulation and cognitive training: A case report.

Purpose: Cognitive impairment secondary to traumatic brain injury (TBI) is difficult to treat and usually results in severe disability. Method: A 48-year-old man presented with chronic refractory headaches and persistent disabling cognitive impairment after TBI. He was first treated with occipital nerve stimulation (ONS) implanted bilaterally to relieve headaches (8 years after the head trauma). Two years later, he was treated with a 6-week protocol combining repetitive transcranial magnetic stimulation (rTMS) delivered to multiple cortical sites (prefrontal cortex, language areas, and areas involved in visuo-spatial functions) and computerized cognitive training (CogT) (targeting memory, language, and visuo-spatial functions) to improve cognitive performance. Results: Executive and cognitive functions (attention, ability to perform calculations, and verbal fluency) improved in association with pain relief after ONS (33-42% improvement) and then improved even more after the rTMS-CogT protocol with an additional improvement of 36-40% on apathy, depression, and anxiety, leading to a significant reduction in caregiver burden. The functional improvement persisted and even increased at 6 months after the end of the rTMS-CogT procedure (10 years after the onset of TBI and 2 years after ONS implantation). Conclusion: This is the first observation describing sustained improvement in post-TBI refractory headache, depression, and cognitive impairment by the association of bilaterally implanted ONS and a combined procedure of multisite rTMS and CogT to target various brain functions.

Additional Benefit of Intraoperative Electroacupuncture in Improving Tolerance of Deep Brain Stimulation Surgical Procedure in Parkinsonian Patients.

BACKGROUND: Deep brain stimulation (DBS) is an effective technique to treat patients with advanced Parkinson's disease. The surgical procedure of DBS implantation is generally performed under local anesthesia due to the need for intraoperative clinical testing. However, this procedure is long (5-7 h on average) and, therefore, the objective that the patient remains co-operative and tolerates the intervention well is a real challenge. OBJECTIVE: To evaluate the additional benefit of electroacupuncture (EA) performed intraoperatively to improve the comfort of parkinsonian patients during surgical DBS implantation. METHODS: This single-center randomized study compared two groups of patients. In the first group, DBS implantation was performed under local anesthesia alone, while the second group received EA in addition. The patients were evaluated preoperatively, during the different stages of the surgery, and 2 days after surgery, using the 9-item Edmonton Symptom Assessment System (ESAS), including a total sum score and physical and emotional subscores. RESULTS: The data of nine patients were analyzed in each group. Although pain and tiredness increased in both groups after placement of the stereotactic frame, the ESAS item "lack of appetite", as well as the ESAS total score and physical subscore increased after completion of the first burr hole until the end of the surgical procedure in the control group only. ESAS total score and physical subscore were significantly higher at the end of the intervention in the control group compared to the EA group. After the surgical intervention (D2), anxiety and ESAS emotional subscore were improved in both groups, but the feeling of wellbeing improved in the EA group only. Finally, one patient developed delirium during the intervention and none in the EA group. DISCUSSION: This study shows that intraoperative electroacupuncture significantly improves the tolerance of DBS surgery in parkinsonian patients. This easy-to-perform procedure could be fruitfully added in clinical practice.

Multi-site rTMS with cognitive training improves apathy in the long term in Alzheimer's disease: A 4-year chart review.

OBJECTIVE: To assess the long-term effects of multi-site repetitive transcranial magnetic stimulation combined with cognitive training (NeuroAD procedure) on cognitive symptoms and apathy in patients with Alzheimer's disease (AD) as part of a 4-year chart review. METHODS: The study included the 30 AD patients who underwent NeuroAD treatment between 2015 and 2019 at our center. The clinical evaluation was based on the Mini Mental State Examination (MMSE), Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Apathy Inventory (AI). Assessment was performed before treatment (baseline), after an initial 6-week protocol of 30 sessions (M1.5), then 3 months (M3), 1 year (M12), and between 1.5 and 4 years (mean 28 months, M28) after treatment initiation. RESULTS: During the first year of follow-up, the AI score improved at all time points (M1.5, M3, M12, p < 0.0001), the ADAS-Cog score improved at the end of the initial procedure (M1.5, p = 0.003) then deteriorated (M12, p = 0.01), while the MMSE score did not change. At final assessment (M28), the AI score was still improved from baseline (p < 0.0001), while the MMSE and ADAS-Cog scores worsened (p < 0.0001). Regarding the ADAS-Cog score, the prolonged improvement at M12 or M28 was correlated with the initial improvement at M1.5. CONCLUSION: The NeuroAD procedure produced long-term improvement in apathy and more general cognitive improvement only in patients who responded well to the initial 6-week protocol. SIGNIFICANCE: Our results suggest long-term beneficial effects of the NeuroAD procedure on apathy, which need to be confirmed in controlled studies. The criteria for predicting a good outcome before starting the procedure remain to be defined.

Diagnostic contribution and therapeutic perspectives of transcranial magnetic stimulation in dementia.

Transcranial magnetic stimulation (TMS) is a powerful tool to probe in vivo brain circuits, as it allows to assess several cortical properties such asexcitability, plasticity and connectivity in humans. In the last 20 years, TMS has been applied to patients with dementia, enabling the identification of potential markers of thepathophysiology and predictors of cognitive decline; moreover, applied repetitively, TMS holds promise as a potential therapeutic intervention. The objective of this paper is to present a comprehensive review of studies that have employed TMS in dementia and to discuss potential clinical applications, from the diagnosis to the treatment. To provide a technical and theoretical framework, we first present an overview of the basic physiological mechanisms of the application of TMS to assess cortical excitability, excitation and inhibition balance, mechanisms of plasticity and cortico-cortical connectivity in the human brain. We then review the insights gained by TMS techniques into the pathophysiology and predictors of progression and response to treatment in dementias, including Alzheimer's disease (AD)-related dementias and secondary dementias. We show that while a single TMS measure offers low specificity, the use of a panel of measures and/or neurophysiological index can support the clinical diagnosis and predict progression. In the last part of the article, we discuss the therapeutic uses of TMS. So far, only repetitive TMS (rTMS) over the left dorsolateral prefrontal cortex and multisite rTMS associated with cognitive training have been shown to be, respectively, possibly (Level C of evidence) and probably (Level B of evidence) effective to improve cognition, apathy, memory, and language in AD patients, especially at a mild/early stage of the disease. The clinical use of this type of treatment warrants the combination of brain imaging techniques and/or electrophysiological tools to elucidate neurobiological effects of neurostimulation and to optimally tailor rTMS treatment protocols in individual patients or specific patient subgroups with dementia or mild cognitive impairment.

Safety and efficacy of an equimolar mixture of oxygen and nitrous oxide: a randomized controlled trial in patients with peripheral neuropathic pain.

ABSTRACT: Nitrous oxide (N2O) is an odorless and colorless gas routinely used as an adjuvant of anesthesia and for short-duration analgesia in various clinical settings mostly in the form of an N2O/O2 50%-50% equimolar mixture (EMONO). Experimental studies have suggested that EMONO could also induce long-lasting analgesic effects related to the blockade of N-methyl-D-aspartate receptors. We designed the first international multicenter proof of concept randomized, placebo-controlled study to assess the efficacy and safety of a 1-hour administration of EMONO or placebo (medical air) on 3 consecutive days up to 1 month after the last administration in patients with chronic peripheral neuropathic pain. A total of 240 patients were recruited in 22 centers in France and Germany and randomly assigned to 1 study group (120 per group). Average pain intensity (primary outcome), neuropathic pain characteristics (Neuropathic Pain Symptom Inventory), Patient Global Impression of Change, anxiety, depression, and quality of life were systematically assessed before and after treatment. The changes in average pain intensity between baseline and 7 days after the last administration were not significantly different between the 2 groups. However, evoked pain intensity (predefined secondary endpoint) and Patient Global Impression of Change (exploratory endpoint) were significantly improved in the EMONO group, and these effects were maintained up to 4 weeks after the last treatment administration. Mostly transient side effects were reported during the treatment administration. These encouraging results provide a basis for further investigation of the long-term analgesic effects of EMONO in patients with neuropathic pain.

Motor cortex stimulation for the treatment of refractory peripheral neuropathic pain.

Epidural motor cortex stimulation (MCS) has been proposed as a treatment for chronic, drug-resistant neuropathic pain of various origins. Regarding pain syndromes due to peripheral nerve lesion, only case series have previously been reported. We present the results of the first randomized controlled trial using chronic MCS in this indication. Sixteen patients were included with pain origin as follows: trigeminal neuralgia (n = 4), brachial plexus lesion (n = 4), neurofibromatosis type-1 (n = 3), upper limb amputation (n = 2), herpes zoster ophthalmicus (n = 1), atypical orofacial pain secondary to dental extraction (n = 1) and traumatic nerve trunk transection in a lower limb (n = 1). A quadripolar lead was implanted, under radiological and electrophysiological guidance, for epidural cortical stimulation. A randomized crossover trial was performed between 1 and 3 months postoperative, during which the stimulator was alternatively switched 'on' and 'off' for 1 month, followed by an open phase during which the stimulator was switched 'on' in all patients. Clinical assessment was performed up to 1 year after implantation and was based on the following evaluations: visual analogue scale (VAS), brief pain inventory, McGill Pain questionnaire, sickness impact profile and medication quantification scale. The crossover trial included 13 patients and showed a reduction of the McGill Pain questionnaire-pain rating index (P = 0.0166, Wilcoxon test) and McGill Pain questionnaire sensory subscore (P = 0.01) when the stimulator was switched 'on' compared to the 'off-stimulation' condition. However, these differences did not persist after adjustment for multiple comparisons. In the 12 patients who completed the open study, the VAS and sickness impact profile scores varied significantly in the follow-up and were reduced at 9-12 months postoperative, compared to the preoperative baseline. At final examination, the mean rate of pain relief on VAS scores was 48% (individual results ranging from 0% to 95%) and MCS efficacy was considered as good or satisfactory in 60% of the patients. Pain relief after 1 year tended to correlate with pain scores at 1 month postoperative, but not with age, pain duration or location, preoperative pain scores or sensory-motor status. Although the results of the crossover trial were slightly negative, which may have been due to carry-over effects from the operative and immediate postoperative phases, observations made during the open trial were in favour of a real efficacy of MCS in peripheral neuropathic pain. Analgesic effects were obtained on the sensory-discriminative rather than on the affective aspect of pain. These results suggest that the indication of MCS might be extended to various types of refractory, chronic peripheral pain beyond trigeminal neuropathic pain.

Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014-2018).

A group of European experts reappraised the guidelines on the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) previously published in 2014 [Lefaucheur et al., Clin Neurophysiol 2014;125:2150-206]. These updated recommendations take into account all rTMS publications, including data prior to 2014, as well as currently reviewed literature until the end of 2018. Level A evidence (definite efficacy) was reached for: high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the painful side for neuropathic pain; HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) using a figure-of-8 or a H1-coil for depression; low-frequency (LF) rTMS of contralesional M1 for hand motor recovery in the post-acute stage of stroke. Level B evidence (probable efficacy) was reached for: HF-rTMS of the left M1 or DLPFC for improving quality of life or pain, respectively, in fibromyalgia; HF-rTMS of bilateral M1 regions or the left DLPFC for improving motor impairment or depression, respectively, in Parkinson's disease; HF-rTMS of ipsilesional M1 for promoting motor recovery at the post-acute stage of stroke; intermittent theta burst stimulation targeted to the leg motor cortex for lower limb spasticity in multiple sclerosis; HF-rTMS of the right DLPFC in posttraumatic stress disorder; LF-rTMS of the right inferior frontal gyrus in chronic post-stroke non-fluent aphasia; LF-rTMS of the right DLPFC in depression; and bihemispheric stimulation of the DLPFC combining right-sided LF-rTMS (or continuous theta burst stimulation) and left-sided HF-rTMS (or intermittent theta burst stimulation) in depression. Level A/B evidence is not reached concerning efficacy of rTMS in any other condition. The current recommendations are based on the differences reached in therapeutic efficacy of real vs. sham rTMS protocols, replicated in a sufficient number of independent studies. This does not mean that the benefit produced by rTMS inevitably reaches a level of clinical relevance.

A practical algorithm for using rTMS to treat patients with chronic pain.

High-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex has a good level of evidence of efficacy as a method for providing analgesic effects in patients with chronic pain. However, there is still no consensus regarding the parameters of stimulation to use and the detailed protocol to apply for therapeutic practice. In this article, we review the main technical points to address, and we propose a practical algorithm of how to use rTMS for chronic pain treatment in daily clinical practice.

The Value of High-Frequency Repetitive Transcranial Magnetic Stimulation of the Motor Cortex to Treat Central Pain Sensitization Associated With Knee Osteoarthritis.

AIM: Chronic pain associated with knee osteoarthritis may develop in connection with a maladaptive process of pain sensitization in the central nervous system. Repetitive transcranial magnetic stimulation (rTMS) has been proposed to treat various pain syndromes related to central sensitization phenomenon, but was never applied in the context of knee osteoarthritis. METHODS: A 71-year-old woman presenting clinical evidence of central sensitization of pain associated with left knee osteoarthritis underwent monthly sessions of rTMS delivered at 10 Hz over the right motor cortex. RESULTS: From the week following the third session, she began to improve on various clinical aspects, including pain. After 10 sessions (i.e., almost one year of follow-up), pain was reduced by 67%, especially regarding neuropathic components, while sleep disorders and fatigue also improved by 57-67%. The central sensitization inventory (CSI) score was reduced by 70%. CONCLUSION: This observation suggests that high-frequency motor cortex rTMS could be a therapeutic option to treat neuropathic pain and psychological symptoms associated with central sensitization developing in the context of chronic osteoarthritis of the knee joint.