The dose-dependent efficiency of radial shock wave therapy for patients with carpal tunnel syndrome: a prospective, randomized, single-blind, placebo-controlled trial.

Recently, extracorporeal shock wave therapy (ESWT) has been shown to be a novel therapy for carpal tunnel syndrome (CTS). However, previous studies did not examine the diverse effects of different-session ESWT for different-grades CTS. Thus, we conducted a randomized, single-blind, placebo-controlled study. Sixty-nine patients (90 wrists) with mild to moderate CTS were randomized into 3 groups. Group A and C patients received one session of radial ESWT (rESWT) and sham eESWT per week for 3 consecutive weeks, respectively; Group B patients received a single session of rESWT. The night splint was also used in all patients. The primary outcome was Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) points, whereas secondary outcomes included the sensory nerve conduction velocity and cross-sectional area of the median nerve. Evaluations were performed at 4, 10, and 14 weeks after the first session of rESWT. Compared to the control group, the three-session rESWT group demonstrated significant BCTQ point reductions at least 14 weeks, and the effect was much longer lasting in patients with moderate CTS than mild CTS. In contrast, the effect of single-session rESWT showed insignificant comparison. rESWT is a valuable strategy for treating CTS and multiple-session rESWT has a clinically cumulative effect.

Long term recovery of median nerve repair using laser-activated chitosan adhesive films.

Sutures remain the standard peripheral nerve repair technique, whether applied directly or indirectly to nerve tissue. Unfortunately, significant postoperative complications can result, such as inflammation, neuroma formation and foreign body reactions. Photochemical-tissue-bonding (PTB) using rose Bengal (RB) integrated into a chitosan bioadhesive is an alternative nerve repair device that removes the need for sutures. Rats were arranged into three groups: RB-chitosan adhesives-repair, end-to-end epineural suture-repair (surgical standard) and sham laser-irradiated control. Groups were compared through histological assessment, electrophysiological recordings and grip motor strength. RB-chitosan adhesive repaired nerves displayed comparable results when compared to the standard suture-repair based on histological and electrophysiological findings. Functionally, RB-chitosan adhesive was associated with a quicker and more pronounced recovery of grip force when compared to the suture-repair.

Impulse propagation along thalamocortical fibers can be detected magnetically outside the human brain.

Orchestrating cortical network activity with synchronous oscillations of neurons across distant regions of the brain underlies information processing in humans (Knight, 2007) and monkeys (Saalmann et al., 2007; Womelsdorf et al., 2007). Frequencies of oscillatory activities depend, to a considerable extent, on the length and conduction velocity of the tracts connecting the neural areas that participate in oscillations (Buzsáki, 2006). However, the impulse propagation along the fiber tracts in the white matter has never been visualized in humans. Here, we show, by recording magnetoencephalogram (MEG) following median nerve stimulation, that a magnetic field component, we labeled "M15," changes dynamically within 1.6-1.8 ms before the onset of magnetic M20 response generated from the primary somatosensory cortex. This new M15 component corresponds to the intracellular depolarizing action current in the thalamocortical fibers propagating with the mean conduction velocity of 29 m/s. The findings challenge the traditional view that MEG is blind to the activity of deep subcortical structures. We argue that the MEG technique holds the promise of providing novel information in impulse transmissions along not only the thalamocortical pathway but also other fiber tracts connecting distant brain areas in humans.

Effect of spinal transcutaneous direct current stimulation on somatosensory evoked potentials in humans.

OBJECTIVE: Invasive stimulation of the spinal cord is used to treat a number of pathological conditions. Aiming to modulate human spinal cord function non-invasively, we evaluated whether transcutaneous direct current (DC) stimulation induces long-lasting changes in conduction along the sensory spinal pathways. METHODS: Somatosensory evoked potentials (SEPs) by posterior tibial nerve and by median nerve stimulation were recorded, before, at current offset and at 20 min after transcutaneous anodal or cathodal DC stimulation over the thoracic spinal cord (2.5 mA, 15 min) in a group of 12 healthy subjects. RESULTS: Whereas both polarities left the spinal (N22) and the cortical potentials (P39) unchanged, anodal transcutaneous spinal DC stimulation decreased significantly by about 25% the amplitude of the cervico-medullary component of posterior tibial nerve SEPs (P30) for at least 20 min. Thoracic transcutaneous spinal cord stimulation left median nerve SEPs unchanged. CONCLUSIONS: Transcutaneous DC stimulation over the thoracic spinal cord induces changes in conduction along human lemniscal pathway that persist after stimulation ends. SIGNIFICANCE: Our results support the use of transcutaneous DC stimulation as a novel tool for non-invasive spinal neuromodulation. Because the method is non-expensive and simple, it can be tested in patients with disorders presently treated with invasive procedures.

Hemispheric asymmetry of hand representation in human primary somatosensory cortex and handedness.

OBJECTIVE: To evaluate interhemispheric differences of hand representation in primary somatosensory (SI) and motor (MI) cortices and its relation to handedness. METHODS: MRI-based EEG dipole source analysis was performed separately for early (P14, N20, P22) and middle/late latency (P30, N60, N110) SEP components after left and right median nerve stimulation. In addition, the location of the MI hand area (Omega region) and handedness were determined. RESULTS: Equivalent current dipoles (ECDs) of N20, P30 and N60 SEP components were localized in contralateral SI (area 3b, N20 and P30; area 1, N60), the mean P22 ECD localization was in area 4 of contralateral MI. In contrast to the Omega region and the precentral P22 component, ECDs in both areas 3b and 1 were located more laterally in the right than in the left hemisphere. ECDs in the right SI lay more laterally than the ipsilateral Omega region. Asymmetry in SI was not correlated with handedness. CONCLUSIONS: The data demonstrate that the location of hand representation shows relevant hemispheric asymmetry in human SI, both in areas 3b and 1. SIGNIFICANCE: Hemispheric asymmetry in SI must be considered in the studies on cortical reorganization and plasticity in SI as well as for transcranial magnetic stimulation (TMS) over SI.

Somatosensory evoked potentials reflect the upper limb motor performance in multiple sclerosis.

OBJECTIVE: The aim of this multicentric study was to multidimensionally evaluate the relationship among somatosensory evoked potentials (SEPs) parameters, patient's perspective and clinical measures of the upper limb impairment in patients with multiple sclerosis (MS). METHODS: We consecutively enrolled 39 MS patients. For median nerve SEPs we acquired the N9, P14, N20 responses and the N9-P14 and P14-N20 interpeak latencies on the dominant side. We also used a validated patient-oriented questionnaire (Disabilities of the Arm, Shoulder and Hand - DASH) and a test of dexterity quantification as the 9-Hole Peg Test (9-HPT). RESULTS: A significant longer time to complete the 9-HPT (p<0.00006) was observed in patients with abnormal SEPs. Patients with undetectable N20 or P14 responses performed the 9-HPT in a significant longer time than patients with detectable responses (p<0.0006 and p<0.001 respectively). Concerning the perspective of patient (evaluated with the DASH questionnaire) significant differences in patients with undetectable P14 response (p<0.01) were observed. CONCLUSIONS: Our data provide further information useful for interpretation of SEPs results, being the median nerve SEPs related to the upper limb performance in MS patients. SIGNIFICANCE: These data increase the significance of SEPs both in clinical practice and in experimental studies in MS.

Increased regional cerebral perfusion in contralateral motor and somatosensory areas after median nerve stimulation therapy.

OBJECTIVE: To evaluate change in regional cerebral perfusion (rCBF) after median nerve stimulation (MNS) therapy in brain-damaged patients. METHODS: Twelve brain-damaged patients received 12 courses of MNS. Technetium-99m-ethyl cysteinate diethylester (99mTc-ECD) SPECT was performed before and 4 weeks after MNS initiation. Clinical response was assessed by Glasglow coma scale or clinical improvement. 12 MNS patients were grouped as good responder (GR) (n = 6) and poor responder (PR) (n = 6) according to therapy response. Scan images were analyzed by Statistical Parametric Mapping 2 (SPM2). RESULTS: In the GR group, paired Student t test between the pre- and post-MNS images showed 2 activation clusters over the left frontal and parietal lobes, including regions of the precentral gyrus, middle frontal gyrus, superior frontal gyrus, subgyral, inferior parietal lobule, and postcentral gyms (corresponding to Brodmann areas 4, 6, and 40). In the PR group, paired Student t test did not show any activation clusters. Clusters with significant differences between the GR and PR groups shared no mutual voxels with those clusters having significant regional effects after MNS in the GR group. CONCLUSIONS: Median nerve stimulation enhanced the rCBF of the contralateral motor and somatosensory cortex, which is compatible with the few previous studies using other modalities.

Subcortical interactions between somatosensory stimuli of different modalities and their temporal profile.

Interactions between inputs of different sensory modality occur along the sensory pathway, including the thalamus. However, the temporal profile of such interaction has not been fully studied. In eight patients who had been implanted an intrathalamic electrode for deep brain stimulation as symptomatic treatment of tremor, we investigated the interactions between mechanical taps and electrical nerve stimuli. Somatosensory evoked potentials (SEPs) were recorded from Erb's point, cervical spinal cord, nucleus ventrointermedialis of the thalamus, and parietal cortex. A handheld electronic reflex hammer was used to deliver a mechanical tap to the skin overlying the first dorsal interosseous muscle and to trigger an ipsilateral digital median nerve electrical stimulus time-locked to the mechanical tap with a variable delay of 0 to 50 ms. There were significant time-dependent interactions between the two sensory volleys at the subcortical level. Thalamic SEPs were decreased in amplitude at interstimulus intervals (ISIs) from 10 to 40 ms with maximum effect at 20 ms (-42.8 +/- 10.5%; P < 0.001). A similar decrease was also seen in the number and frequency of the high-frequency components of thalamic SEPs (-25 +/- 4%). A smaller reduction (-18.1 +/- 5.8%; P < 0.001) was present in upper cervical response at ISI = 20 ms. There were no changes in peripheral responses. Cortical SEPs were almost completely absent in some subjects at ISIs from 20 to 50 ms. There were no changes in SEP latencies. Our results indicate that significant time-dependent interactions between sensory volleys occur at the subcortical level. These observations provide further insight into the physiological mechanisms underlying afferent gating between sensory volleys of different modality.

Quantitative analysis of MEG using modified sLORETA for clinical application.

OBJECTIVE: To determine whether standardised low-resolution brain electromagnetic tomography modified for a quantifiable method (sLORETA-qm) can be used for quantitative analysis in magnetoencephalography (MEG). METHODS: Somatosensory evoked fields (SEFs) were obtained from 10 hemispheres of five healthy volunteers stimulated on the median nerve at 0.75, 1.0, 1.25, 1.5, 1.75 and 2.0 x threshold of thenar muscle twitch (TMT). N20 m intensity changes were analysed quantitatively using sLORETA-qm. Then, SEFs were measured with stimulation on the median nerve at 1.5 x TMT from 47 hemispheres in 24 subjects. sLORETA-qm intensity and the equivalent current dipole (ECD) moment of N20 m were calculated, and relationships between the values were evaluated. RESULTS: sLORETA-qm intensity increased linearly with stimulus intensity between 0.75 and 1.5 x TMT, and tended to reach a plateau or decrease at higher stimulus intensities. The distribution of sLORETA-qm intensity after natural logarithmic transformation was normal and a close correlation was found between the ECD moment and sLORETA-qm intensity (r(s)=0.91, p<0.001). CONCLUSIONS: The results of this study focusing on N20 m suggested that sLORETA-qm is reliable for quantitative analysis of MEG as well as ECD models. SIGNIFICANCE: sLORETA-qm appears promising for quantitative analyses of MEG for which ECD models are inappropriate.

Somatosensory-evoked fields on magnetoencephalography for epilepsy infants younger than 4 years with total intravenous anesthesia.

OBJECTIVE: Patients must remain immobile for magnetoencephalography (MEG) and MRI recordings to allow precise localization of brain function for pre-surgical functional mapping. In young children with epilepsy, this is accomplished with recordings during sleep or with anesthesia. This paper demonstrates that MEG can detect, characterize and localize somatosensory-evoked fields (SEF) in infants younger than 4 years of age with or without total intravenous anesthesia (TIVA). METHODS: We investigated the latency, amplitude, residual error (RE) and location of the N20m of the SEF in 26 infants (mean age=2.6 years). Seventeen patients underwent TIVA and 9 patients were tested while asleep, without TIVA. RESULTS: MEG detected 44 reliable SEFs (77%) in 52 median nerve stimulations. We found 27 reliable SEFs (79%) with TIVA and 13 reliable SEFs (72%) without TIVA. TIVA effects included longer latencies (p<0.001) and lower RE (p<0.05) compared to those without TIVA. Older patients and larger head circumferences also showed significantly shorter latencies (p<0.01). CONCLUSIONS: TIVA resulted in reliable SEFs with lower RE and longer latencies. SIGNIFICANCE: MEG can detect reliable SEFs in infants younger than 4 years old. When infants require TIVA for MEG and MRI acquisition, SEFs can still be reliably observed.

Homeostatic metaplasticity in the human somatosensory cortex.

Long-term potentiation (LTP) and long-term depression (LTD) are regulated by homeostatic control mechanisms to maintain synaptic strength in a physiological range. Although homeostatic metaplasticity has been demonstrated in the human motor cortex, little is known to which extent it operates in other cortical areas and how it links to behavior. Here we tested homeostatic interactions between two stimulation protocols -- paired associative stimulation (PAS) followed by peripheral high-frequency stimulation (pHFS) -- on excitability in the human somatosensory cortex and tactile spatial discrimination threshold. PAS employed repeated pairs of electrical stimulation of the right median nerve followed by focal transcranial magnetic stimulation of the left somatosensory cortex at an interstimulus interval of the individual N20 latency minus 15 msec or N20 minus 2.5 msec to induce LTD- or LTP-like plasticity, respectively [Wolters, A., Schmidt, A., Schramm, A., Zeller, D., Naumann, M., Kunesch, E., et al. Timing-dependent plasticity in human primary somatosensory cortex. Journal of Physiology, 565, 1039-1052, 2005]. pHFS always consisted of 20-Hz trains of electrical stimulation of the right median nerve. Excitability in the somatosensory cortex was assessed by median nerve somatosensory evoked cortical potential amplitudes. Tactile spatial discrimination was tested by the grating orientation task. PAS had no significant effect on excitability in the somatosensory cortex or on tactile discrimination. However, the direction of effects induced by subsequent pHFS varied with the preconditioning PAS protocol: After PAS(N20-15), excitability tended to increase and tactile spatial discrimination threshold decreased. After PAS(N20-2.5), excitability decreased and discrimination threshold tended to increase. These interactions demonstrate that homeostatic metaplasticity operates in the human somatosensory cortex, controlling both cortical excitability and somatosensory skill.

The relationship between frontal somatosensory-evoked potentials and motor planning.

Performance of efficient and precise movement requires the proper planning of motor parameters as well as the integration of sensory feedback. This study tests the hypothesis that the frontal components of the median nerve somatosensory-evoked potentials are differentially modulated, depending on (i) the stage of motor preparation and (ii) the moving limb. Participants were instructed to make intermittent voluntary contractions with either their right or left hands while receiving median nerve stimulation to the right wrist only. The results indicate that the frontal N30 demonstrated a significant increase in amplitude during the execution, but not the preparation, of a movement contralateral to median nerve stimulation. These data have implications for interhemispheric control of sensory information within the primary and premotor cortices.

Cortical and brainstem LTP-like plasticity in Huntington's disease.

Recent studies have reported abnormalities in short-term plasticity in patients with Huntington's disease (HD). However, is not known whether long-term potentiation (LTP)-like plasticity is also affected in these patients. We tested cortical and brainstem LTP-like plasticity in eight symptomatic HD patients and in 10 healthy age-matched controls. To probe motor cortex LTP-like plasticity we used paired associative stimulation (PAS), a technique that combines repetitive electric stimulation of the median nerve with subsequent transcranial magnetic stimulation (TMS) of the contralateral motor cortex at 25 ms. To investigate brainstem plasticity, we induced LTP-like phenomena in the trigeminal wide dynamic range neurons (WDR) of the blink reflex circuit by pairing an high-frequency train of electrical stimuli (HFS) over the right supraorbital nerve (SO) coincident with the R2 response elicited by a preceding SO stimulus. Our results demonstrate impairment of both cortical and brainstem LTP-like plasticity in symptomatic HD patients which is similar to LTP deficits previously reported in HD animal models. These findings might well represent the neurophysiological correlates of memory deficits often present in HD.

Pulsed radiofrequency of the median nerve under ultrasound guidance.

Neuropathy of the median nerve within the carpal tunnel (carpal tunnel syndrome) has an age adjusted incidence of 105 cases per 100,000 person years. Treatment of carpal tunnel syndrome ranges from conservative management with medication and exercise to surgical release of the median nerve. Conservative treatment accounts for a significant portion of resources utilized and includes splinting, nerve gliding, ultrasound, and carpal bone mobilization. Recurrent symptoms of carpal tunnel syndrome have been shown to occur in 0% to 19% of patients following carpal tunnel release, with up to 12% requiring re-exploration. Prognosis for re-exploration is not as good as for primary carpal tunnel release, with a high recurrence rate in some populations. Ultrasound has seen increasing use in regional anesthesia and has been shown to improve the quality of regional anesthetic blocks. Pulsed radiofrequency was developed with the goal of providing reduction in pain from the use of electrical fields in the absence of neural injury. The use of ultrasound guidance for positioning radiofrequency probes over peripheral nerves has not been reported. This case report describes the use of ultrasound guided pulsed radiofrequency in the treatment of recurrent carpal tunnel syndrome. Following revision carpal tunnel surgery, the patient in this report was unable to obtain relief of pain in either hand with medication therapy alone. After a successful diagnostic median nerve block at the cubital fossa, pulsed radiofrequency of the median nerve was performed on the left side at the cubital fossa, under ultrasound guidance. Radiofrequency probe adjustment around the nerve was conducted under live ultrasound guidance and multiple pulsed treatments were applied at anatomically distinct sites over the nerve. A 70% reduction in pain was reported over the follow up period of 12 weeks.

Optimal method to determine the stimulus intensity for median nerve somatosensory evoked potentials.

To find the best method to determine the stimulus intensity for median nerve somatosensory evoked potentials (SEP), we tried to activate muscle or cutaneous branch as preferentially as possible by using ordinary surface stimulation. We minutely moved the stimulating electrode at the wrist in normal subjects and changed the stimulus intensity stepwise at each site. We evaluated the correlation between the amplitudes of the SEP components and peripheral parameters such as the relative intensities to the motor threshold (rMT) or the sensory threshold (rST) and the amplitude of the sensory nerve action potential recorded over the index finger (SNAP2) or that of the compound muscle action potential (CMAP). The sensory parameters (rST and SNAP2) showed better correlation with SEP amplitude than the motor parameters (rMT and CMAP). In an extreme case, stimulation 40% over the motor threshold elicited no N9 response and only a small N20. Adjusting the stimulus intensity at slightly above the motor threshold, as recommended by most guidelines, in such a case would result in an erroneous result. We propose the stimulus intensity resulting in SNAP2 amplitude of 80% of its maximum as the optimal method because it consistently gave almost saturated SEP responses.

Mechanical and focal electrical stimuli applied to the skin of the index fingertip induce both inhibition and excitation in low-threshold flexor carpi radialis motor units.

It has been observed that mechanical stimulation of the skin of the index fingertip causes a weak short-latency inhibition followed by a strong long-lasting facilitation of the flexor carpi radialis (FCR) H-reflex. Based on threshold and latency, these cutaneous reflexes are thought to be routed to motoneurons by parallel pathways. As recent studies have shown predominant inhibitory potentials in slow motoneurons and predominant excitatory potentials in faster ones, the question arises as to whether or not the two cutaneous pathways converge onto the same motoneuron. The poststimulus time histogram technique was used to investigate the changes in firing frequency of low-threshold FCR motor units (MUs), induced by passive mechanical or focal electrical stimuli to the index skin. After gently tapping the finger pulp a small sharp inhibition appeared in 20 MUs. On average, inhibition started 10.2 +/- 1.6 ms from the homonymous Ia monosynaptic effect, and its central delay was estimated to be 1.2 +/- 1.6 ms. The subsequent facilitation, more consistent, had a mean latency of 13.5 +/- 1.7 ms. Inhibition and excitation were statistically significant (P < 0.05). A similar biphasic effect was observed in seven other FCR-MUs, also after focal electrical stimulation of the same skin area. Comparison with the time course of the H-reflex, representing the whole population of MUs, showed striking similarities in time course and latency to the present MU effect. It is thus suggested that cutaneous spinal pathways may have a homogeneous distribution within the FCR motoneuron pool, and that the skewed distribution of cutaneous afferents onto motoneurons should be not taken as a rule.

Multiple measures of axonal excitability in peripheral sensory nerves: an in vivo rat model.

Excitability measurements on human motor and sensory nerves have provided new insights into axonal membrane changes in peripheral nerve disorders. The aim of this study was to establish an in vivo rat preparation suitable for threshold tracking of sensory nerve action potentials (SNAPs) to model clinical sensory nerve excitability studies. In Sprague-Dawley rats anesthetized with ketamine and xylazine, current stimuli were applied to the base of the tail and SNAPs recorded from distal needle electrodes. Multiple excitability data were obtained as previously described for human nerves and compared to recordings from the motor tail axons and to sensory recordings from human median and ulnar nerves. The pattern of excitability changes in rats was broadly similar to that in humans, although some parameters differed significantly. Individual recordings were stable for at least 3 h. These data show that the rat tail enables excitability properties of sensory as well as motor axons to be studied experimentally, e.g., in models of nerve disease and during pharmacological interventions.

Homeostatic plasticity in human motor cortex demonstrated by two consecutive sessions of paired associative stimulation.

Long-term potentiation (LTP) and long-term depression (LTD) underlie most models of learning and memory, but neural activity would grow or shrink in an uncontrolled manner, if not guarded by stabilizing mechanisms. The Bienenstock-Cooper-Munro (BCM) rule proposes a sliding threshold for LTP/LTD induction: LTP induction becomes more difficult if neural activity was high previously. Here we tested if this form of homeostatic plasticity applies to the human motor cortex (M1) in vivo by examining the interactions between two consecutive sessions of paired associative stimulation (PAS). PAS consisted of repeated pairs of electrical stimulation of the right median nerve followed by transcranial magnetic stimulation of the left M1. The first PAS session employed an interstimulus interval equalling the individual N20-latency of the median nerve somatosensory-evoked cortical potential plus 2 ms, N20-latency minus 5 ms, or a random alternation between these intervals, to induce an LTP-like increase in motor-evoked potential (MEP) amplitudes in the right abductor pollicis brevis muscle (PAS(LTP)), an LTD-like decrease (PAS(LTD)), or no change (PAS(Control)), respectively. The second PAS session 30 min later was always PAS(LTP). It induced an moderate LTP-like effect if conditioned by PAS(Control), which increased if conditioned by PAS(LTD), but decreased if conditioned by PAS(LTP). Effects on MEP amplitude induced by the second PAS session exhibited a negative linear correlation with those in the first PAS session. Because the two PAS sessions activate identical neuronal circuits, we conclude that 'homosynaptic-like' homeostatic mechanisms in accord with the BCM rule contribute to regulating plasticity in human M1.

Somatosensory evoked potentials in attention deficit/hyperactivity disorder and tic disorder.

OBJECTIVE: Both attention deficit/hyperactivity disorder (ADHD) and chronic tic disorder (TD) are hyperkinetic disorders. These disorders often coexist with each other and frequently have sensory components. Therefore, we hypothesized that they might have a common pathophysiology involving the somatosensory system, especially hyper-excitabilities of primary somatosensory area. METHODS: To evaluate sensory system excitability, we examined somatosensory evoked potentials (SEP) elicited by median nerve stimulation in 18 children with ADHD and 18 children with TD. RESULTS: Three children with ADHD and 8 children with TD showed giant SEP and the peak-to-peak amplitude for N20-P25 was also significantly greater than that obtained from normally developing children (P<0.05 for ADHD and P<0.01 for TD). Children with TD had significant left-ward asymmetry of N20-P25 (P<0.01) and higher left-hemispheric N20-P25 than children with ADHD (P<0.05). CONCLUSIONS: Although hyper-excitability of the primary somatosensory area is a common characteristic for ADHD and TD, its severity, especially in the left-hemisphere, differs (i.e. TD has left-ward hyper-excitability). SIGNIFICANCE: The possibility remains that hyper-excitability of the primary somatosensory area is a reason why these disorders often coexist with each other and left-ward hyper-excitability of the primary somatosensory area is a unique feature of TD described for the first time.