Analgesic effects of navigated motor cortex rTMS in patients with chronic neuropathic pain.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) can relieve neuropathic pain when applied at high frequency (HF: 5-20 Hz) over the primary motor cortex (M1), contralateral to pain side. In most studies, rTMS is delivered over the hand motor hot spot (hMHS), whatever pain location. Navigation systems have been developed to guide rTMS targeting, but their value to improve rTMS efficacy remains to be demonstrated. OBJECTIVE: To compare the analgesic efficacy of HF-rTMS targeting the hMHS (non-navigated procedure) or the M1 representation of the pain region (navigated procedure). METHODS: The analgesic effect of a single session of 10 Hz-rTMS of M1 was assessed in 66 patients with neuropathic pain of various causes and locations, according to three conditions: sham or active non-navigated rTMS of the hMHS and active navigated rTMS of the pain region. RESULTS: Pain was relieved by both active rTMS conditions, and not by sham. Pain location influenced the results: upper or lower limb pain was significantly relieved, but not facial or hemibody pain. Pain relief lasted 1 week only after navigated rTMS, compared to sham. CONCLUSION: Navigation may improve HF-rTMS efficacy in patients with limb pain, whereas targeting remains to be optimized for more diffuse or facial pain. WHAT DOES THIS STUDY ADD?: To produce analgesic effects, HF-rTMS should be applied over the precentral cortex contralaterally to the painful side. Although the hMHS is the target normally chosen for stimulation, the optimal target has not been defined yet. Neuronavigational methods have been recently developed; they allow the integration of MRI data and are thought to improve rTMS efficacy.

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

BACKGROUND AND PURPOSE: 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. METHODS: The functional cortical effects of high-dose steroids in 21 MS patients before and after 3 days of intravenous administration of methylprednisolone (1 g/day) for the treatment of MS relapse were studied. Investigations included various clinical scales [Kurtzke Functional System Scale (KFSS), Expanded Disability Status Scale and Fatigue Severity Scale, 10-m walk] and transcranial magnetic stimulation (TMS) tests of cortical excitability [resting motor threshold, recruitment curve of motor evoked potentials, short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) at various interstimuli intervals (ISIs), cortical silent period and interhemispheric inhibition]. RESULTS: Following steroid administration, clinical improvement was significant for the KFSS pyramidal (motor) and total scores, whilst TMS showed a reduction of SICI (mean and maximum values) and an increase of ICF at 10 ms ISI. CONCLUSIONS: Very rapid functional changes in the excitability of cortical circuits involved in motor control can be induced by steroids, before any process of remyelination or axonal regeneration has time to occur. The net effect of steroids on the balance between intracortical GABAergic inhibition and glutamatergic facilitation was in favour of weaker inhibition or stronger facilitation, which could lead to improving the motor performance in MS patients.

Rapidly progressive amyotrophic lateral sclerosis initially masquerading as a demyelinating neuropathy.

Rare cases of demyelinating neuropathy have been described in association with amyotrophic lateral sclerosis (ALS). We report two patients with typical ALS whose initial electroneuromyographic (ENMG) presentation could suggest the existence of a process of motor nerve fiber demyelination. However, subsequent ENMG examinations and the fatal course of the disease in a few months rather supported severe ongoing axonal degeneration at the origin of motor nerve conduction abnormalities. Repeated examinations could be required to distinguish between ENMG features of concomitant demyelinating neuropathy and rapidly progressive motor neuron loss in ALS.

Pure ipsilateral central facial palsy and contralateral hemiparesis secondary to ventro-medial medullary stroke.

Medullary infarcts are occasionally associated with facial palsy of the central type (C-FP). This finding can be explained by the course of the facial corticobulbar (F-CB) fibers. It is believed that fibers that project to the upper facial muscles decussate at the level of the facial nucleus, whereas those destined to the lower facial muscles decussate more caudally, at the level of the mid or upper medulla. It has been proposed that the lower F-CB fibers descend ventromedially near the corticospinal tract to the upper medulla where they cross midline and ascend dorsolaterally. Accordingly, ventromedial medullary infarcts are expected to result in contralateral facial and limb weakness. We report a patient with a medial medullary infarct restricted to the right pyramid and associated with ipsilateral C-FP and contralateral hemiparesis. The neurological findings are discussed in light of the hypothetical course of the F-CB fibers in the medulla.

Definition of DLPFC and M1 according to anatomical landmarks for navigated brain stimulation: inter-rater reliability, accuracy, and influence of gender and age.

The optimization of the targeting of a defined cortical region is a challenge in the current practice of transcranial magnetic stimulation (TMS). The dorsolateral prefrontal cortex (DLPFC) and the primary motor cortex (M1) are among the most usual TMS targets, particularly in its "therapeutic" application. This study describes a practical algorithm to determine the anatomical location of the DLPFC and M1 using a three-dimensional (3D) brain reconstruction provided by a TMS-dedicated navigation system from individual magnetic resonance imaging (MRI) data. The coordinates of the right and left DLPFC and M1 were determined in 50 normal brains (100 hemispheres) by five different investigators using a standardized procedure. Inter-rater reliability was good, with 95% limits of agreement ranging between 7 and 16 mm for the different coordinates. As expressed in the Talairach space and compared with anatomical or imaging data from the literature, the coordinates of the DLPFC defined by our algorithm corresponded to the junction between BA9 and BA46, while M1 coordinates corresponded to the posterior border of hand representation. Finally, we found an influence of gender and possibly of age on some coordinates on both rostrocaudal and dorsoventral axes. Our algorithm only requires a short training and can be used to provide a reliable targeting of DLPFC and M1 between various TMS investigators. This method, based on an image-guided navigation system using individual MRI data, should be helpful to a variety of TMS studies, especially to standardize the procedure of stimulation in multicenter "therapeutic" studies.

Pain-related evoked potentials: a comparative study between electrical stimulation using a concentric planar electrode and laser stimulation using a CO2 laser.

OBJECTIVE: To compare the pain-related evoked potentials (PREPs) obtained by superficial electrical stimulation using a concentric planar electrode to those obtained by CO2 laser stimulation. METHODS: In 12 healthy subjects, PREPs, sympathetic skin reflexes (SSRs), motor reaction times (mRTs), and the conduction velocity (CV) of the recruited nerve fibres were assessed in response to electrical and laser stimulation. RESULTS: In response to superficial electrical stimulation, PREP latencies and mRTs were shorter, while PREP amplitude tended to be increased. By contrast, SSR amplitudes and latencies and estimated CVs of the stimulated nerve fibres did not differ between electrical and laser stimulation. Fifteen minutes after PREP recordings, the residual pain intensity and the degree of unpleasantness were higher for laser stimulation than for electrical stimulation. In addition, CO2 laser stimuli induced dyschromic spots on the skin. For these reasons, all subjects declared that they would prefer superficial electrical stimulation rather than CO2 laser stimulation if they had to perform PREPs again. CONCLUSIONS: The estimated CVs of the recruited nerve fibres and the localized pinprick sensation felt by the subjects suggest that small-diameter fibres in the A-delta range, conveying "first-pain" information, were stimulated in response to superficial electrical stimulation as for laser stimulation. Superficial electrical stimulation using a concentric planar electrode could be a valuable alternative to laser stimulation for assessing PREPs in the practice of clinical neurophysiology.

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

BACKGROUND: '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. METHODS: In 14 patients with chronic refractory neuropathic pain, navigated rTMS was targeted over M1 hand region, contralateral to painful side. Analgesic effects were daily assessed on a visual analogue scale for the week after each 10 Hz-rTMS session, preceded or not by TBS priming. In an additional experiment, the effects on cortical excitability parameters provided by single- and paired-pulse TMS paradigms were studied. RESULTS: Pain level was reduced after any type of rTMS procedure compared to baseline, but iTBS priming produced greater analgesia than the other protocols. Regarding motor cortex excitability changes, the analgesic effects were associated with an increase in intracortical inhibition, whatever the type of stimulation, primed or non-primed. CONCLUSIONS: The present results show that the analgesic effects of 'conventional' 10 Hz-rTMS delivered to M1 can be enhanced by TBS priming, at least using iTBS. Interestingly, the application of cTBS and iTBS did not produce opposite modulations, unlike previously reported in other systems. It remains to be determined whether the interest of TBS priming is to generate a simple additive effect or a more specific process of cortical plasticity.

Comparison of "standard" and "navigated" procedures of TMS coil positioning over motor, premotor and prefrontal targets in patients with chronic pain and depression.

Since about 15 years, transcranial magnetic stimulation (TMS) is used as a technique to investigate the function of specific cortical regions. Single pulse TMS studies have targeted the dorsolateral premotor cortex (dlPMC) to characterize premotor-motor interactions in movement disorders. Repetitive TMS (rTMS) trials have targeted the dorsolateral prefrontal cortex (dlPFC) to treat depression. In almost all previous studies, these targets have been defined according to a "standard" scalp distance to the site of stimulation evoking motor responses of maximal amplitude in the contralateral hand ("hand motor hotspot" corresponding to the primary motor cortex, M1). The "standard" procedure of coil positioning locates the dlPMC and dlPFC as 2-3 and 5cm, respectively, anterior to the "hand motor hotspot". The aim of our study was to compare the locations of M1, dlPMC and dlPFC targets provided by the "standard" procedure of coil positioning and those provided by using a neuronavigation system integrating individual brain magnetic resonance imaging (MRI). Twenty-two patients were enrolled, all being treated for depressive symptoms in the context of chronic pain syndrome. The centers of the dlPMC and dlPFC regions were accurately targeted by the "standard" procedure in 14 and eight patients (64 and 36% of the series), respectively. In the other patients, the "standard" procedure located the dlPMC target on the M1/dlPMC border and the dlPFC target on the dlPMC/dlPFC border. On average, the MRI-guided location of M1, dlPMC, and dlPFC was, respectively, 6.1mm posterior, 31.7mm anterior and 69.0mm anterior to the "hand motor hotspot". The "standard" procedure failed to accurately locate the dlPMC and dlPFC targets by about 1 and 2cm, respectively. A statistical analysis of the MRI coordinates (x, y, z) of the targets revealed that the M1 target was more posterior, the dlPMC target more superficial and the dlPFC target more anterior, lateral, and deeper, using neuronavigation compared to the "standard" procedure. This study confirms that the "standard" procedure of coil positioning is not accurate to target a desired cortical region. Target location can be improved by the use of a navigation system taking individual brain anatomy into account. The present results incline to be cautious on the pathophysiological interpretations of previous results reported in TMS studies based on "standard" targeting, e.g. regarding premotor-motor interactions. Similarly, the inaccuracy of the "standard" procedure of coil positioning could partly explain the between-study variability of the therapeutic effects produced by rTMS in patients with depression. Our results strongly support a more anterior and lateral placement of the TMS coil for dlPFC stimulation in the treatment of depression.

A reappraisal of the value of lateral spread response monitoring in the treatment of hemifacial spasm by microvascular decompression.

BACKGROUND: Lateral spread response (LSR) to the electrical stimulation of a facial nerve branch is a specific electrophysiological feature of primary hemifacial spasm (HFS). The curative treatment of HFS is based on surgical microvascular decompression (MVD). However, the outcome of this procedure is not always satisfactory. OBJECTIVE: To evaluate the correlation between intraoperative LSR changes and the short- and long-term postoperative clinical outcome following MVD. METHODS: Thirty-two consecutive patients with primary HFS treated by MVD performed with intraoperative LSR monitoring were retrospectively included. The patients were assessed for the presence of HFS and surgical complications at 1 day, 1 month and 6 months after surgery. The long-term clinical result was assessed between 1 and 10 years (mean 5.4 years) using a self-report questionnaire. RESULTS: Patients were divided into three groups based on intraoperative LSR changes: (1) in 15 patients, LSRs were present before incision and disappeared after MVD (47%); (2) in nine patients, LSRs were present before incision but persisted despite MVD (28%); (3) in eight patients, LSRs were absent before surgery and remained so after the procedure (25%). Intraoperative LSR abolition during the MVD procedure correlated with HFS relief in the long term (p<0.0001, Fisher exact test), but not on the first day after surgery (p = 0.3564). CONCLUSIONS: Monitoring MVD by recording LSRs intraoperatively could be of value not only to indicate the resolution of the vasculonervous conflict at the end of surgery, but also to predict a successful clinical outcome in the long term after the surgical intervention.