Theta-burst versus 20 Hz repetitive transcranial magnetic stimulation in neuropathic pain: A head-to-head comparison.

OBJECTIVE: High-frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to reduce neuropathic pain, but intermittent "theta-burst" stimulation (iTBS) could be a better alternative because of shorter duration and greater ability to induce cortical plasticity. Here we compared head-to-head the pain-relieving efficacy of the two modalities when applied daily for 5 days to patients with neuropathic pain. METHODS: Forty-six patients received 20 Hz-rTMS and/or iTBS protocols and 39 of them underwent the full two procedures in a random cross-over design. They rated pain intensity, sleep quality, fatigue and general health status daily during 5 consecutive weeks. RESULTS: Pain relief during the month following stimulation was superior after 20 Hz-rTMS relative to iTBS (F(1,38) = 4.645; p = 0.037). Correlation between respective levels of maximal relief showed a significant deviation toward the 20 Hz-rTMS effect. A greater proportion of individuals responded to 20 Hz-rTMS (52% vs 32%, 95 %CI[0.095-3.27]; p = 0.06), and reports of fatigue significantly improved after 20 Hz-rTMS relative to iTBS (p = 0.01). General health and sleep quality scores did not differentiate both techniques. CONCLUSIONS: High-frequency rTMS appeared superior to iTBS for neuropathic pain relief. SIGNIFICANCE: Adequate matching between the oscillatory activity of motor cortex and that of rTMS may increase synaptic efficacy, thus enhancing functional connectivity of motor cortex with distant structures involved in pain regulation.

EEG analysis in anti-NMDA receptor encephalitis: Description of typical patterns.

OBJECTIVE: To describe different electroencephalogram (EEG) patterns and epileptic features in patients with anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE), their timeline in the course of the disease, their correlation with clinical data and outcome. METHODS: We retrospectively analyzed EEG recordings between November 2007 and June 2016 in 24 consecutive patients. RESULTS: Three EEG patterns were described: Excessive Beta Activity range 14-20 Hz (EBA) in 71% of patients, Extreme Delta Brush (EDB) in 58% and Generalized Rhythmic Delta Activity (GRDA) in 50%. They followed a chronological organization in the course of the disease: EBA appeared first, followed by EDB and then GRDA, as the median time of appearance for EBA, EDB and GRDA was respectively 10, 16.5 and 21.5 days. The presence of GRDA was strongly associated with concomitant abnormal movements (p < 0.001). CONCLUSION: This study focuses on EEG and epileptic abnormalities in anti-NMDARE. Beyond EDB that were already reported (Schmitt et al., 2012), GRDA seems to be a very frequent pattern. Its rhythmic aspect should not be misinterpreted as seizure or status epilepticus, to avoid antiepileptic treatments intensification. SIGNIFICANCE: This study comforts the importance of EEG in anti-NMDARE, with a better description of EEG abnormalities for a better treatment management.

Epilepsy surgery: A therapeutic patient education program.

Before the creation of a therapeutic patient education (TPE) program for epilepsy surgery, a needs analysis was conducted with 29 people, including patients (n=13), family members (n=9) and healthcare providers (n=7). Most of them highlighted the psychological difficulties of the surgical process, and the need for considerably more precise information concerning the immediate postoperative period. In addition, several patients and/or family members requested meeting with a patient who had undergone the surgery. The majority of subjects were interested in epilepsy-surgery TPE. These data were important in the creation of our TPE program and, more generally, for the management of these patients.

Diagnostic accuracy of quantitative EEG to detect delayed cerebral ischemia after subarachnoid hemorrhage: A preliminary study.

OBJECTIVE: Delayed cerebral ischemia (DCI) is the most important and preventable morbidity cause after subarachnoid hemorrhage (SAH). Therefore, DCI early detection is a major challenge. Yet, neurological examination can be unreliable in poor grade SAH patients. EEG provides information from most superficial cortical area, with ischemia-related changes. This study aims at defining an alpha-theta/delta (AT/D) ratio decrease thresholds to detect DCI. METHODS: We used EEG with a montage matching vascular territories (right and left anterior central and posterior) and compared them to follow-up brain imaging. RESULTS: 15 SAH patients (Fischer ≥ 3, World Federation of Neurological Surgeons scale ≥4, 9 DCI) were monitored during 6.4 [4-8] days (min = 2d, max = 13d). AT/D changes could follow three different patterns: (1) prolonged or (2) transient decrease and (3) no decrease or progressive increase. A regional 30% decrease outlasting 3.7 h reached 100% sensitivity and 88.9% specificity to detect DCI. Only 22.6% were in a zone of uncertain diagnosis (3.7-8.04 h). These prolonged decreases, with a loss of transient changes, started in cortical areas evolving toward DCI, and preceded intracranial changes when available. CONCLUSION: Although this study has a small sample size, prolonged AT/D decrease seems to be a reliable biomarker of DCI. SIGNIFICANCE: cEEG changes are likely to precede cerebral infarction and could be useful at the bedside to detect DCI before irreversible damage.

Somatotopic effects of rTMS in neuropathic pain? A comparison between stimulation over hand and face motor areas.

BACKGROUND: The therapeutic influence of somatotopic matching between pain topography and motor cortex stimulation site for neuropathic pain (NP) remains controversial. METHODS: Thirty-two patients suffering from NP involving the upper limb (n = 20) or the face (n = 12) received two high-frequency rTMS neuronavigated sessions targeting hand and face motor cortical areas, versus placebo. The cortical target was defined by anatomical MRI and EMG responses in all patients, completed in 19 of them by functional MRI. Sessions were separated by at least 2 weeks and applied in random order. Pain relief was assessed using numerical rating scale (NRS). RESULTS: In terms of percentage of pain relief, rTMS over the hand motor area was significantly superior to both face rTMS and placebo. When comparing pre- and post-NRS scores, a significant decrease in pain was observed after hand area rTMS for the two pain localizations, while stimulation of the face area induced a slight but nonsignificant effect on upper limb pain after correction. Sham-rTMS did not exert any effect. The percentage of patients with clinically significant (>30%) or mild (15-30%) pain relief did not differ, however, between rTMS addressed to the hand or face area. CONCLUSIONS: The results do not support a somatotopic effect of motor rTMS for NP. Lack of clinically relevant somatotopic effects in upper limb or face pain suggests that much of the rTMS analgesic effect may depend on high-order mechanisms involving cognitive and affective appraisal of pain, rather than on a sensory effect related to the specific motor area stimulated. SIGNIFICANCE: Strict somatotopic targeting of rTMS does not appear warranted for the treatment of upper limb or face NP. Since the hand motor area is easier to target and provides better results, it might be privileged for both types of pain.

[Electrophysiological testing in spinal cord tumors]. / Les explorations neurophysiologiques dans les tumeurs médullaires.

Evoked potentials (EPs) are useful to evaluate the functional impairment of motor and somatosensory pathways in spinal cord tumors. Conduction through pyramidal tracts is evaluated by motor EPs (MEPs) elicited by transcranial stimulation, magnetic for awake patients or electric in the operating room. Somatosensory EPs (SEPs) and laser EPs (LEPs) are complementary procedures to explore conduction in dorsal columns and spinothalamic tracts, respectively. MEPs as well as SEPs show conduction abnormalities in about 60% of cases with a sensitivity that increases up to 70% when both procedures are carried out. Abnormalities are observed in the absence of any clinical sign in respectively 7% and 15% of cases for MEPs and SEPs. Multilevel stimulations for SEPs recordings permit to detect segmental dysfunction in 70% in case of cervical TIM, even in the absence of clinical signs. LEPs are useful in specific clinical situations: they allow a dermatomal stimulation and are correlated to segmental thermoalgic anaesthesia. Electrophysiological testing plays an important role in the diagnostic and therapeutic strategy: before surgery, MEPs and SEPs objectively evaluate the functional impairment directly related to the lesion. They also help by permitting a follow-up, either before surgery when the surgical decision is delayed because of a good clinical tolerance of the lesion, or after operation to evaluate the functional evolution. Intraoperative monitoring of MEPs and SEPs allows informing the surgeon about the impact on each surgical manipulation. No prospective randomized study has been performed to date to compare clinical evolution after surgery with or without monitoring. Nevertheless, a wide consensus became established in favor of monitoring to limit the risk of postoperative definite deficit and to permit an optimal surgical resection without risk when responses are preserved.

Somatosensory evoked potentials in the assessment of peripheral neuropathies: Commented results of a survey among French-speaking practitioners and recommendations for practice.

BACKGROUND: Somatosensory evoked potentials (SSEPs) are increasingly performed for the assessment of peripheral neuropathies, but no practical guidelines have yet been established in this specific application. STUDY AIM: To determine the relevant indication criteria and optimal technical parameters for SSEP recording in peripheral neuropathy investigation. METHODS: A survey was conducted among the French-speaking practitioners with experience of SSEP recording in the context of peripheral neuropathies. The results of the survey were analyzed and discussed to provide recommendations for practice. RESULTS: SSEPs appear to be a second-line test when electroneuromyographic investigation is not sufficiently conclusive, providing complementary and valuable information on central and proximal peripheral conduction in the somatosensory pathways. CONCLUSIONS: Guidelines for a standardized recording protocol, including the various parameters to be measured, are proposed. CLINICAL RELEVANCE: We hope that these proposals will help to recognize the value of this technique in peripheral neuropathy assessment in clinical practice.

French recommendations on electroencephalography.

Electroencephalography allows the functional analysis of electrical brain cortical activity and is the gold standard for analyzing electrophysiological processes involved in epilepsy but also in several other dysfunctions of the central nervous system. Morphological imaging yields complementary data, yet it cannot replace the essential functional analysis tool that is EEG. Furthermore, EEG has the great advantage of being non-invasive, easy to perform and allows repeat testing when follow-up is necessary, even at the patient's bedside. Faced with advances in knowledge, techniques and indications, the Société de neurophysiologie clinique de langue française (SNCLF) and the Ligue française contre l'épilepsie (LFCE) found it necessary to provide an update on EEG recommendations. This article will review the methodology applied to this work, refine the various topics detailed in the following chapters. It will go over the summary of recommendations for each of these chapters and highlight proposals for writing an EEG report. Some questions could not be answered by review of the literature; in such cases, in addition to the guidelines the working and reading groups provided their expert opinion.

Continuous EEG monitoring in adults in the intensive care unit (ICU).

Continuous EEG monitoring in the ICU is different from planned EEG due to the rather urgent nature of the indications, explaining the fact that recording is started in certain cases by the clinical team in charge of the patient's care. Close collaboration between neurophysiology teams and intensive care teams is essential. Continuous EEG monitoring can be facilitated by quantified analysis systems. This kind of analysis is based on certain signal characteristics, such as amplitude or frequency content, but raw EEG data should always be interpreted if possible, since artefacts can sometimes impair quantified EEG analysis. It is preferable to work within a tele-EEG network, so that the neurophysiologist has the possibility to give an interpretation on call. Continuous EEG monitoring is thus useful in the diagnosis of non-convulsive epileptic seizures or purely electrical discharges and in the monitoring of status epilepticus when consciousness disorders persist after initial treatment. A number of other indications are currently under evaluation.

[French guidelines on electroencephalogram]. / Recommandations françaises sur l'électroencéphalogramme.

Electroencephalography allows the functional analysis of electrical brain cortical activity and is the gold standard for analyzing electrophysiological processes involved in epilepsy but also in several other dysfunctions of the central nervous system. Morphological imaging yields complementary data, yet it cannot replace the essential functional analysis tool that is EEG. Furthermore, EEG has the great advantage of being non-invasive, easy to perform and allows control tests when follow-up is necessary, even at the patient's bedside. Faced with the advances in knowledge, techniques and indications, the Société de Neurophysiologie Clinique de Langue Française (SNCLF) and the Ligue Française Contre l'Épilepsie (LFCE) found it necessary to provide an update on EEG recommendations. This article will review the methodology applied to this work, refine the various topics detailed in the following chapters. It will go over the summary of recommendations for each of these chapters and underline proposals for writing an EEG report. Some questions could not be answered by the review of the literature; in those cases, an expert advice was given by the working and reading groups in addition to the guidelines.

[A national framework for educational programs in epileptic patients, children and adults]. / Un référentiel national pour l'éducation thérapeutique des patients atteints d'épilepsie(s), enfants et adultes.

Epilepsy is a chronic disease with a wide range of presentations occurring at any age. It affects the patient's quality of life, implying a need for numerous healthcare services. Therapeutic education programs (TEPs) are designed to match patient age, disease course, and individual learning abilities. In France, these programs are proposed by the national health authorities (Superior Health Authority), and authorized by the Regional Health Agencies. Two years ago, a Therapeutic Education Programs Commission (TEPC), supported by the French League against Epilepsy (FLAE), was created. The goal was to bring together representative healthcare professionals in a working group in order to standardize practices. This led to the creation of a national reference of healthcare skills specific for children and adults with epilepsy. Five tables, for five "life periods", outline the framework of this professional reference tool. Program personalization, an essential part of TEPs, is necessary to develop a creative atmosphere. This slow process is specific to the various stages of life and can be influenced by the occurrence of various handicaps. Family and caregivers make key contributions to the process. The national framework for therapeutic education in epilepsy serves as a central crossroad where professions can find essential information to create or adapt their own TEPs. In the near future, regional experiences will be documented and collected for regular updates. This professional therapeutic education network will help promote therapeutic education programs and facilitate standard practices. Finally, several TEP files and tools will be shared on the FLAE website available for professional access. Today, the group's goal is to achieve national deployment of this "referential" framework.

Optimal parameters of transcranial electrical stimulation for intraoperative monitoring of motor evoked potentials of the tibialis anterior muscle during pediatric scoliosis surgery.

OBJECTIVE: Transcranial electric stimulation elicited muscle motor evoked potentials (TESmMEPs) is one of the best methods for corticospinal tract's function monitoring during spine and spinal cord surgeries. A train of multipulse electric stimulation is required for eliciting TESmMEPs under general anaesthesia. Here, we investigated the best stimulation parameters for eliciting and recording tibialis anterior's TESmMEPs during paediatric scoliosis surgery. PATIENTS AND METHODS: Numbers of pulses (NOP), inter-stimulus intervals (ISI) and current intensities allowing the best size tibialis anterior muscle's TESmMEPs under general anaesthesia, were tested and collected during 77 paediatric scoliosis surgery monitoring procedures in our hospital. Individual pulse duration was kept at 0.5 ms and stimulating electrodes were positioned at C1 and C2 (International 10-20-EEG-System) during all the tests. RESULTS: The NOP used for eliciting the best tibialis anterior TESmMEPs response was 5, 6, and 7 respectively in 21 (27%), 47 (61%) and 9 (12%) out of the 77 patients. The ISI was 2, 3 and 4 ms respectively in 13 (17%), 55 (71%) and 9 (12%) of them. The current intensity used varied from 300 to 700 V (mean: 448±136 V). CONCLUSION: Most patients had 6 as best NOP (61%) and 3 ms as best ISI (71%). These findings support that a NOP of 6 and an ISI of 3 ms should be preferentially used as optimal stimulation settings for intraoperative tibialis anterior muscle's TESmMEPs eliciting and recording during paediatric scoliosis surgery.

Intraoperative neurophysiologic monitoring in spine surgery. Developments and state of the art in France in 2011.

Intraoperative spinal cord monitoring consists in a subcontinuous evaluation of spinal cord sensory-motor functions and allows the reduction the incidence of neurological complications resulting from spinal surgery. A combination of techniques is used: somatosensory evoked potentials (SSEP), motor evoked potentials (MEP), neurogenic motor evoked potentials (NMEP), D waves, and pedicular screw testing. In absence of intraoperative neurophysiological testing, the intraoperative wake-up test is a true form of monitoring even if its latency long and its precision variable. A 2011 survey of 117 French spinal surgeons showed that only 36% had neurophysiological monitoring available (public healthcare facilities, 42%; private facilities, 27%). Monitoring can be performed by a neurophysiologist in the operating room, remotely using a network, or directly by the surgeon. Intraoperative alerts allow real-time diagnosis of impending neurological injury. Use of spinal electrodes, moved along the medullary canal, can determine the lesion level (NMEP, D waves). The response to a monitoring alert should take into account the phase of the surgical intervention and does not systematically lead to interruption of the intervention. Multimodal intraoperative monitoring, in presence of a neurophysiologist, in collaboration with the anesthesiologist, is the most reliable technique available. However, no monitoring technique can predict a delayed-onset paraplegia that appears after the end of surgery. In cases of preexisting neurological deficit, monitoring contributes little. Monitoring of the L1-L4 spinal roots also shows low reliability. Therefore, monitoring has no indication in discal and degenerative surgery of the spinal surgery. However, testing pedicular screws can be useful. All in all, thoracic and thoracolumbar vertebral deviations, with normal preoperative neurological examination are currently the essential indication for spinal cord monitoring. Its absence in this indication is a lost opportunity for the patient. If neurophysiological means are not available, intraoperative wake-up test is a minimal obligation.

[Neurophysiological evaluation of cortical excitability in migraine: a review of the literature]. / Évaluation électrophysiologique de l'excitabilité corticale dans la migraine.

INTRODUCTION: Neurophysiological studies point to altered cortical neuronal excitability in migraine patients. STATE OF ART: Between attacks, migraine brain seems to be "hyperresponsive" to repetitive stimuli, as suggested by evoked potential studies that show a lack of habituation to sensory stimuli. Transcranial magnetic stimulation suggests an impairment of intracortical inhibitory circuits in migraine, especially in migraine with aura. Controversial results are obtained in migraineurs without aura. Repetitive transcranial magnetic stimulation also shows in migraine with aura a paradoxical enhancement of intracortical facilitation by low frequency stimulation and greater increased facilitatory mechanisms by high-frequency stimulation. Importantly, cortical excitability level fluctuates over time in relation to the migraine cycle. The interictal lack of habituation to sensory stimuli normalizes before and during a migraine attack. Changes of cortical excitability consistent with the theory of cortical spreading depression are also observed during migraine aura with magnetoencephalography. PERSPECTIVES: The exact role of cortical excitability changes in migraine pathophysiology and possibly in chronic migraine is still unknown. Further studies are also necessary to clarify the role of migraine preventive drugs on brain excitability. CONCLUSIONS: In this review, the results of neurophysiological studies conducted in migraine patients will be described and the associated pathophysiological hypotheses will be discussed.

[French guidelines on the use of repetitive transcranial magnetic stimulation (rTMS): safety and therapeutic indications]. / Recommandations françaises sur l'utilisation de la stimulation magnétique transcrânienne répétitive (rTMS) : règles de sécurité et indications thérapeutiques.

During the past decade, a large amount of work on transcranial magnetic stimulation (TMS) has been performed, including the development of new paradigms of stimulation, the integration of imaging data, and the coupling of TMS techniques with electroencephalography or neuroimaging. These accumulating data being difficult to synthesize, several French scientific societies commissioned a group of experts to conduct a comprehensive review of the literature on TMS. This text contains all the consensual findings of the expert group on the mechanisms of action, safety rules and indications of TMS, including repetitive TMS (rTMS). TMS sessions have been conducted in thousands of healthy subjects or patients with various neurological or psychiatric diseases, allowing a better assessment of risks associated with this technique. The number of reported side effects is extremely low, the most serious complication being the occurrence of seizures. In most reported seizures, the stimulation parameters did not follow the previously published recommendations (Wassermann, 1998) [430] and rTMS was associated to medication that could lower the seizure threshold. Recommendations on the safe use of TMS / rTMS were recently updated (Rossi et al., 2009) [348], establishing new limits for stimulation parameters and fixing the contraindications. The recommendations we propose regarding safety are largely based on this previous report with some modifications. By contrast, the issue of therapeutic indications of rTMS has never been addressed before, the present work being the first attempt of a synthesis and expert consensus on this topic. The use of TMS/rTMS is discussed in the context of chronic pain, movement disorders, stroke, epilepsy, tinnitus and psychiatric disorders. There is already a sufficient level of evidence of published data to retain a therapeutic indication of rTMS in clinical practice (grade A) in chronic neuropathic pain, major depressive episodes, and auditory hallucinations. The number of therapeutic indications of rTMS is expected to increase in coming years, in parallel with the optimisation of stimulation parameters.

[Autoimmune autonomic ganglionopathy: a case series of six patients and literature review]. / Ganglionopathie autonomique auto-immune : une série de six observations et revue de la littérature.

PURPOSE: Auto-immune autonomic ganglionopathy is a recently described clinical entity within the spectrum of autonomic neuropathies. Patients with auto-immune autonomic ganglionopathy typically present with rapid onset of severe autonomic failure. Acetylcholine receptor ganglionic antibodies, directed against ganglionic synapsis, disrupt synaptic transmission in autonomic ganglia and lead to autonomic failure. These antibodies are specific for auto-immune autonomic ganglionopathy and are present in 50% of patients. METHODS: Descriptive retrospective study. We report six French patients who presented with auto-immune autonomic ganglionopathy diagnosed between 1996 and 2002. RESULTS: Four patients were men and the median age at diagnosis was 45 years. All patients presented with a subacute autonomic failure with constant severe orthostatic hypotension. Serological testing of acetylcholine receptor ganglionic antibodies was performed in four out of the six patients and was found positive in three. All the patients received intravenous immunoglobulin and a clinical improvement was observed in four of them. CONCLUSION: Auto-immune autonomic ganglionopathy is an unusual and overlooked disorder. However, this autonomic neuropathy deserves to be better known as most of the patients respond to immunomodulatory therapy.

Pain relief by rTMS: differential effect of current flow but no specific action on pain subtypes.

OBJECTIVES: To assess, against placebo, the pain-relieving effects of high-rate repetitive transcranial magnetic stimulation (rTMS) on neuropathic pain. METHODS: Double-blind, randomized, cross-over study of high-rate rTMS against placebo in 28 patients. The effect of a change in coil orientation (posteroanterior vs lateromedial) on different subtypes of neuropathic pain was further tested in a subset of 16 patients. Pain relief was evaluated daily during 1 week. RESULTS: High-frequency, posteroanterior rTMS decreased pain scores significantly more than placebo. Posteroanterior rTMS also outmatched placebo in a score combining subjective (pain relief, quality of life) and objective (rescue drug intake) criteria of treatment benefit. Changing the orientation of the coil from posteroanterior to lateromedial did not yield any significant pain relief. The analgesic effects of posteroanterior rTMS lasted for approximately 1 week. The pain-relieving effects were observed exclusively on global scores reflecting the most distressing type of pain in each patient. Conversely, rTMS did not modify specifically any of the pain subscores that were separately tested (ongoing, paroxysmal, stimulus-evoked, or disesthesic pain). CONCLUSIONS: Posteroanterior repetitive transcranial magnetic stimulation (rTMS) was more effective than both placebo and lateromedial rTMS. When obtained, pain relief was not specific of any particular submodality, but rather reduced the global pain sensation whatever its type. This is in accord with recent models of motor cortex neurostimulation, postulating that its analgesic effects may derive in part from modulation of the affective appraisal of pain, rather than a decrease of its sensory components.

Myoclonus-dystonia: clinical and electrophysiologic pattern related to SGCE mutations.

OBJECTIVE: To clarify the clinical and neurophysiologic spectrum of myoclonus-dystonia patients with mutations of the SGCE gene. METHODS: We prospectively studied 41 consecutive patients from 22 families with documented mutations of the SGCE gene. The patients had a standardized interview, neurologic examination, and detailed neurophysiologic examination, including surface polymyography, long-loop C-reflex studies, and EEG jerk-locked back averaging. RESULTS: We noted a homogeneous electrophysiologic pattern of myoclonus of subcortical origin with short jerks (mean 95 msec, range 25 to 256 msec) at rest, during action, and during posture; there were no features of cortical hyperexcitability (specifically no abnormal C-reflex response and no short-latency premyoclonic potential on back-averaging studies). Myoclonus was either isolated or associated with mild to moderate dystonia, and predominated in the neck/trunk or proximal upper limbs in most cases. We found that 22% of the patients had a spontaneous improvement in their dystonia before reaching adulthood and that hypotonia can occasionally be a presenting symptom of the disorder. CONCLUSION: We describe the myoclonus in patients with mutations in the SGCE gene and characterize the electrophysiologic pattern of this myoclonus. This pattern may help to improve the sensitivity of molecular tests and to define homogeneous populations suitable for inclusion in therapeutic trials.