Samar S. Ayache

Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS)

A group of European experts was commissioned to establish guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS) from evidence published up until March 2014, regarding pain, movement disorders, stroke, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, consciousness disorders, tinnitus, depression, anxiety disorders, obsessive-compulsive disorder, schizophrenia, craving/addiction, and conversion. Despite unavoidable inhomogeneities, there is a sufficient body of evidence to accept with level A (definite efficacy) the analgesic effect of high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the pain and the antidepressant effect of HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC). A Level B recommendation (probable efficacy) is proposed for the antidepressant effect of low-frequency (LF) rTMS of the right DLPFC, HF-rTMS of the left DLPFC for the negative symptoms of schizophrenia, and LF-rTMS of contralesional M1 in chronic motor stroke. The effects of rTMS in a number of indications reach level C (possible efficacy), including LF-rTMS of the left temporoparietal cortex in tinnitus and auditory hallucinations. It remains to determine how to optimize rTMS protocols and techniques to give them relevance in routine clinical practice. In addition, professionals carrying out rTMS protocols should undergo rigorous training to ensure the quality of the technical realization, guarantee the proper care of patients, and maximize the chances of success. Under these conditions, the therapeutic use of rTMS should be able to develop in the coming years.

Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS)

A group of European experts was commissioned by the European Chapter of the International Federation of Clinical Neurophysiology to gather knowledge about the state of the art of the therapeutic use of transcranial direct current stimulation (tDCS) from studies published up until September 2016, regarding pain, Parkinsons disease, other movement disorders, motor stroke, poststroke aphasia, multiple sclerosis, epilepsy, consciousness disorders, Alzheimers disease, tinnitus, depression, schizophrenia, and craving/addiction. The evidence-based analysis included only studies based on repeated tDCS sessions with sham tDCS control procedure; 25 patients or more having received active treatment was required for Class I, while a lower number of 10-24 patients was accepted for Class II studies. Current evidence does not allow making any recommendation of Level A (definite efficacy) for any indication. Level B recommendation (probable efficacy) is proposed for: (i) anodal tDCS of the left primary motor cortex (M1) (with right orbitofrontal cathode) in fibromyalgia; (ii) anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) (with right orbitofrontal cathode) in major depressive episode without drug resistance; (iii) anodal tDCS of the right DLPFC (with left DLPFC cathode) in addiction/craving. Level C recommendation (possible efficacy) is proposed for anodal tDCS of the left M1 (or contralateral to pain side, with right orbitofrontal cathode) in chronic lower limb neuropathic pain secondary to spinal cord lesion. Conversely, Level B recommendation (probable inefficacy) is conferred on the absence of clinical effects of: (i) anodal tDCS of the left temporal cortex (with right orbitofrontal cathode) in tinnitus; (ii) anodal tDCS of the left DLPFC (with right orbitofrontal cathode) in drug-resistant major depressive episode. It remains to be clarified whether the probable or possible therapeutic effects of tDCS are clinically meaningful and how to optimally perform tDCS in a therapeutic setting. In addition, the easy management and low cost of tDCS devices allow at home use by the patient, but this might raise ethical and legal concerns with regard to potential misuse or overuse. We must be careful to avoid inappropriate applications of this technique by ensuring rigorous training of the professionals and education of the patients.

Analgesic effects of repetitive transcranial magnetic stimulation of the motor cortex in neuropathic pain: Influence of theta burst stimulation priming

‘Conventional’ protocols of high‐frequency repetitive transcranial magnetic stimulation (rTMS) delivered to M1 can produce analgesia. Theta burst stimulation (TBS), a novel rTMS paradigm, is thought to produce greater changes in M1 excitability than ‘conventional’ protocols. After a preliminary experiment showing no analgesic effect of continuous or intermittent TBS trains (cTBS or iTBS) delivered to M1 as single procedures, we used TBS to prime a subsequent session of ‘conventional’ 10 Hz‐rTMS.

Transcranial magnetic stimulation of the brain: guidelines for pain treatment research

Abstract Recognizing that electrically stimulating the motor cortex could relieve chronic pain sparked development of noninvasive technologies. In transcranial magnetic stimulation (TMS), electromagnetic coils held against the scalp influence underlying cortical firing. Multiday repetitive transcranial magnetic stimulation (rTMS) can induce long-lasting, potentially therapeutic brain plasticity. Nearby ferromagnetic or electronic implants are contraindications. Adverse effects are minimal, primarily headaches. Single provoked seizures are very rare. Transcranial magnetic stimulation devices are marketed for depression and migraine in the United States and for various indications elsewhere. Although multiple studies report that high-frequency rTMS of the motor cortex reduces neuropathic pain, their quality has been insufficient to support Food and Drug Administration application. Harvards Radcliffe Institute therefore sponsored a workshop to solicit advice from experts in TMS, pain research, and clinical trials. They recommended that researchers standardize and document all TMS parameters and improve strategies for sham and double blinding. Subjects should have common well-characterized pain conditions amenable to motor cortex rTMS and studies should be adequately powered. They recommended standardized assessment tools (eg, NIHs PROMIS) plus validated condition-specific instruments and consensus-recommended metrics (eg, IMMPACT). Outcomes should include pain intensity and qualities, patient and clinician impression of change, and proportions achieving 30% and 50% pain relief. Secondary outcomes could include function, mood, sleep, and/or quality of life. Minimum required elements include sample sources, sizes, and demographics, recruitment methods, inclusion and exclusion criteria, baseline and posttreatment means and SD, adverse effects, safety concerns, discontinuations, and medication-usage records. Outcomes should be monitored for at least 3 months after initiation with prespecified statistical analyses. Multigroup collaborations or registry studies may be needed for pivotal trials.

Stroke rehabilitation using noninvasive cortical stimulation: motor deficit

Noninvasive cortical stimulation (NICS) has been used during the acute, postacute and chronic poststroke phases to improve motor recovery in stroke patients having upper- and/or lower-limb paresis. This paper reviews the rationale for using the different NICS modalities to promote motor stroke rehabilitation. The changes in cortical excitability after stroke and the possible mechanisms of action of cortical stimulation in this context are outlined. A number of open and placebo-controlled trials have investigated the clinical effect of repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) of the primary motor cortex in patients with motor stroke. These studies attempted to improve motor performance by increasing cortical excitability in the stroke-affected hemisphere (via high-frequency rTMS or anodal tDCS) or by decreasing cortical excitability in the contralateral hemisphere (via low-frequency rTMS or cathodal tDCS). The goal of these studies was to reduce the inhibition exerted by the unaffected hemisphere on the affected hemisphere and to then restore a normal balance of interhemispheric inhibition. All these NICS techniques administered alone or in combination with various methods of neurorehabilitation were found to be safe and equally effective at the short term on various aspects of poststroke motor abilities. However, the long-term effect of NICS on motor stroke needs to be further evaluated before considering the use of such a technique in the daily routine management of stroke.

Fatigue in Multiple Sclerosis: Neural Correlates and the Role of Non-Invasive Brain Stimulation

Multiple sclerosis (MS) is a chronic progressive inflammatory disease of the central nervous system (CNS) and the major cause of non-traumatic disability in young adults. Fatigue is a frequent symptom reported by the majority of MS patients during their disease course and drastically affects their quality of life. Despite its significant prevalence and impact, the underlying pathophysiological mechanisms are not well elucidated. MS fatigue is still considered the result of multifactorial and complex constellations, and is commonly classified into “primary” fatigue related to the pathological changes of the disease itself, and “secondary” fatigue attributed to mimicking symptoms, comorbid sleep and mood disorders, and medications side effects. Radiological, physiological, and endocrine data have raised hypotheses regarding the origin of this symptom, some of which have succeeded in identifying an association between MS fatigue and structural or functional abnormalities within various brain networks. Hence, the aim of this work is to reappraise the neural correlates of MS fatigue and to discuss the rationale for the emergent use of noninvasive brain stimulation (NIBS) techniques as potential treatments. This will include a presentation of the various NIBS modalities and a suggestion of their potential mechanisms of action in this context. Specific issues related to the value of transcranial direct current stimulation (tDCS) will be addressed.

Non-invasive Brain Stimulation Therapy in Multiple Sclerosis: A Review of tDCS, rTMS and ECT Results

BACKGROUND Multiple sclerosis (MS) is a disabling neurological disorder presenting a variety of symptoms which are hard to control by actual drug regimens. Non-invasive brain stimulation (NIBS) techniques have been investigated in the past years for the improvement of several neurologic and psychiatric disorders. OBJECTIVE Here, we review the application of transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (rTMS, iTBS) and electroconvulsive therapy (ECT) in MS patients. METHODS Articles were searched in common literature databases. Crosslinks were reviewed. RESULTS ECT was shown to be efficacious for the treatment of severe psychiatric disorders in 21 case reports. The results of tDCS and TMS for the treatment of depressive symptoms, fatigue, tactile sensory deficit, pain, motor performance, and spasticity were assessed in several studies and showed mixed results. CONCLUSIONS Overall, data for the treatment of MS with NIBS is sparse regarding TMS and tDCS. Treatment of severe psychiatric disorders with ECT is only reported in single cases. More studies are needed to elucidate the potential role of NIBS in MS treatment.

Prefrontal tDCS Decreases Pain in Patients with Multiple Sclerosis.

Background: In the last few years, transcranial direct current stimulation (tDCS) has emerged as an appealing therapeutic option to improve brain functions. Promising data support the role of prefrontal tDCS in augmenting cognitive performance and ameliorating several neuropsychiatric symptoms, namely pain, fatigue, mood disturbances, and attentional impairment. Such symptoms are commonly encountered in patients with multiple sclerosis (MS). Objective: The main objective of the current work was to evaluate the tDCS effects over the left dorsolateral prefrontal cortex (DLPFC) on pain in MS patients.Our secondary outcomes were to study its influence on attention, fatigue, and mood. Materials and Methods: Sixteen MS patients with chronic neuropathic pain were enrolled in a randomized, sham-controlled, and cross-over study.Patients randomly received two anodal tDCS blocks (active or sham), each consisting of three consecutive daily tDCS sessions, and held apart by 3 weeks. Evaluations took place before and after each block. To evaluate pain, we used the Brief Pain Inventory (BPI) and the Visual Analog Scale (VAS). Attention was assessed using neurophysiological parameters and the Attention Network Test (ANT). Changes in mood and fatigue were measured using various scales. Results: Compared to sham, active tDCS yielded significant analgesic effects according to VAS and BPI global scales.There were no effects of any block on mood, fatigue, or attention. Conclusion: Based on our results, anodal tDCS over the left DLPFC appears to act in a selective manner and would ameliorate specific symptoms, particularly neuropathic pain. Analgesia might have occurred through the modulation of the emotional pain network. Attention, mood, and fatigue were not improved in this work. This could be partly attributed to the short protocol duration, the small sample size, and the heterogeneity of our MS cohort. Future large-scale studies can benefit from comparing the tDCS effects over different cortical sites, changing the stimulation montage, prolonging the duration of protocol, and coupling tDCS with neuroimaging techniques for a better understanding of its possible mechanism of action.

Relapses in multiple sclerosis: effects of high-dose steroids on cortical excitability

High‐dose steroid administration is the usual treatment of multiple sclerosis (MS) relapse, but it remains to determine whether this treatment may act by changing the excitability of cortical circuitry.

Stroke rehabilitation using noninvasive cortical stimulation: hemispatial neglect

The rehabilitation of neuropsychological sequels of cerebral stroke such as hemispatial neglect by noninvasive cortical stimulation (NICS) attracts increasing attention from the scientific community. The NICS techniques include primarily repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). They are based on the concept of either reactivating a hypoactive cortical region affected by the stroke (the right hemisphere in case of neglect) or reducing cortical hyperactivity of the corresponding cortical region in the contralateral hemisphere (the left hemisphere). In the studies published to date on the topic of neglect rehabilitation, rTMS was used to inhibit the left parietal cortex and tDCS to either activate the right or inhibit the left parietal cortex. Sham-controlled NICS studies assessed short-term effects, whereas long-term effects were only assessed in noncontrolled rTMS studies. Further controlled studies of large series of patients are necessary to determine the best parameters of stimulation (including the optimal cortical target location) according to each subtype of neglect presentation and to the time course of stroke recovery. To date, even if there are serious therapeutic perspectives based on imaging data and experimental studies, the evidence is not compelling enough to recommend any particular NICS protocol to treat this disabling condition in clinical practice.