[Neurological complications of nitrous oxide consumption. A case report]. / Complicaciones neurológicas del consumo de óxido nitroso. A propósito de un caso.

TITLE: Complicaciones neurológicas del consumo de óxido nitroso. A propósito de un caso.

Efecto analgésico del baclofeno intratecal a largo plazo sobre el dolor neuropático en pacientes con lesión medular / The long-term analgesic effect of intrathecal baclofen on neuropathic pain in patients with spinal cord injury

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[Non-invasive brain and spinal cord stimulation for motor and functional recovery after a spinal cord injury]. / Estimulación no invasiva cerebral y medular para la recuperación motora y funcional tras una lesión medular.

INTRODUCTION: Spinal cord injury is a traumatic or non-traumatic event that causes an alteration of sensory, motor or autonomic functioning and ultimately affects the physical, psychological and social well-being of the person who suffers it. A comprehensive approach to spinal cord injury requires many health resources and can place a considerable financial burden on patients, their families and the community. AIM: To review the literature published to date on the use of non-invasive brain stimulation, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and transcutaneous non-invasive spinal cord stimulation (tcSCS), as therapeutic strategies to improve the functionality of patients with spinal cord injury. The studies were grouped as addressing either non-invasive brain stimulation or non-invasive spinal cord stimulation. DEVELOPMENT: Altogether 32 studies were identified: 21 involving brain stimulation (14 in rTMS and 7 in tDCS) and 11 with spinal cord stimulation (tcSCS). All the studies were conducted in adult patients who had undergone a spinal cord injury. Despite significant variability in treatment protocols, patient characteristics and clinical assessment, the changes observed were reported in almost all the studies without producing any side effects and with motor or functional improvement. CONCLUSION: Non-invasive brain stimulation, as well as spinal cord stimulation, are promising techniques for the rehabilitation of patients with spinal cord injury due to their novelty, effectiveness and minimal side effects.

TITLE: Estimulación no invasiva cerebral y medular para la recuperación motora y funcional tras una lesión medular.Introducción. La lesión medular es un evento traumático o no traumático que causa una alteración de la función sensorial, motora o autonómica y, en última instancia, afecta a las características físicas, psicológicas y el bienestar social de la persona que lo sufre. El abordaje integral de la lesión medular requiere muchos recursos de salud y puede representar una considerable carga financiera para los pacientes, sus familias y la comunidad. Objetivo. Revisar la bibliografía publicada sobre el uso de la estimulación cerebral no invasiva, incluida la estimulación magnética transcraneal repetitiva (EMTr), la estimulación de corriente continua directa transcraneal (tDCS), así como la estimulación medular no invasiva transcutánea (tcSCS), como estrategias terapéuticas para mejorar la funcionalidad de los pacientes con lesión medular. Los estudios se agruparon bien como de estimulación no invasiva cerebral, bien como de estimulación medular no invasiva. Desarrollo. Se identificaron 32 estudios: 21 de estimulación cerebral (14 en EMTr y 7 en tDCS) y 11 de estimulación medular (tcSCS). Todos los estudios se realizaron en pacientes adultos que sufrieron una lesión medular. A pesar de la variabilidad significativa en los protocolos de tratamiento, las características de los pacientes y la evaluación clínica, los cambios observados se describieron en casi todos los estudios sin producir efectos secundarios con mejoría motora o funcional. Conclusión. La estimulación cerebral no invasiva, así como la estimulación medular, son técnicas prometedoras para la rehabilitación de pacientes con lesión medular debido a su novedad, su efectividad y mínimos efectos secundarios.

Focal vibration in neurorehabilitation.

During the last decade, many studies have been carried out to understand the effects of focal vibratory stimuli at various levels of the central nervous system and to study pathophysiological mechanisms of neurological disorders as well as the therapeutic effects of focal vibration in neurorehabilitation. This review aimed to describe the effects of focal vibratory stimuli in neurorehabilitation including the neurological diseases or disorders like stroke, spinal cord injury, multiple sclerosis, Parkinson's' disease and dystonia. In conclusion, focal vibration stimulation is well tolerated, effective and easy to use, and it could be used to reduce spasticity, to promote motor activity and motor learning within a functional activity, even in gait training, independent from etiology of neurological pathology. Further studies are needed in the future well-designed trials with bigger sample size to determine the most effective frequency, amplitude and duration of vibration application in the neurorehabilitation.

The effects of transcranial direct current stimulation with visual illusion in neuropathic pain due to spinal cord injury: an evoked potentials and quantitative thermal testing study.

BACKGROUND: Neuropathic pain (NP) is common in spinal cord injury (SCI) patients. One of its manifestations is a lowering of pain perception threshold in quantitative thermal testing (QTT) in dermatomes rostral to the injury level. Transcranial direct current stimulation (tDCS) combined with visual illusion (VI) improves pain in SCI patients. We studied whether pain relief with tDCS + VI intervention is accompanied by a change in contact heat- evoked potentials (CHEPs) or in QTT. METHODS: We examined 18 patients with SCI and NP before and after 2 weeks of daily tDCS + VI intervention. Twenty SCI patients without NP and 14 healthy subjects served as controls. We assessed NP intensity using a numerical rating scale (NRS) and determined heat and pain thresholds with thermal probes. CHEPs were recorded to stimuli applied at C4 level, and subjects rated their perception of evoked pain using NRS during CHEPs. RESULTS: Thirteen patients reported a mean decrease of 50% in the NRS for NP after tDCS + VI. Evoked pain perception was significantly higher than in the other two groups, and reduced significantly together with CHEPs amplitude after tDCS + VI with respect to baseline. Pain perception threshold was significantly lower than in the other two groups before tDCS + VI intervention, and increased significantly afterwards. CONCLUSION: Two weeks of tDCS + VI induced significant changes in CHEPs, evoked pain and heat pain threshold in SCI patients with NP. These neurophysiological tests might be objective biomarkers of treatment effects for NP in patients with SCI.

Effect of intrathecal baclofen on evoked pain perception: an evoked potentials and quantitative thermal testing study.

BACKGROUND AND OBJECTIVES: Somatic antinociceptive effects of baclofen have been demonstrated in animal models. We hypothesized that if enhanced thermal or pain sensitivity is produced by loss of gamma-aminobutyric acid (GABA)-ergic tone in the central nervous system, spinal administration of GABA agonists might be predicted to be effective in thermal and/or pain perception changes and pain-related evoked potentials in candidates for intrathecal baclofen (ITB) treatment. METHODS: Eleven patients with severe spinal cord injury (SCI) who suffered from severe spasticity were evaluated during a 50-µg ITB bolus test. Warm and heat pain thresholds, evoked heat pain perception, and contact heat-evoked potentials (CHEPs) were determined above SCI level from the right and left sides. Nine age- and gender-matched healthy volunteers undergoing repeat testing without any placebo injection served as control group. RESULT: In patients, heat pain perception threshold increased, and evoked pain perception and amplitude of CHEPs decreased significantly after ITB bolus application in comparison with baseline (p < 0.005), with no change in warm perception threshold. In controls, no significant changes were observed in repeat testing over time. CONCLUSION: Our findings indicate that ITB modulates heat pain perception threshold, evoked heat pain perception and heat pain-related evoked potentials without inducing warm perception threshold changes in SCI patients. This phenomenon should be taken into account in the clinical evaluation and management of pain in patients receiving baclofen.

Motor and gait improvement in patients with incomplete spinal cord injury induced by high-frequency repetitive transcranial magnetic stimulation.

OBJECTIVE: To assess the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) on lower extremities motor score (LEMS) and gait in patients with motor incomplete spinal cord injury (SCI). METHOD: The prospective longitudinal randomized, double-blind study assessed 17 SCI patients ASIA D. We assessed LEMS, modified Ashworth Scale (MAS), 10-m walking test (10MWT), Walking Index for SCI (WISCI II) scale, step length, cadence, and Timed Up and Go (TUG) test at baseline, after the last of 15 daily sessions of rTMS and 2 weeks later. Patients were randomized to active rTMS or sham stimulation. Three patients from the initial group of 10 randomized to sham stimulation entered the active rTMS group after a 3-week washout period. Therefore a total of 10 patients completed each study condition. Both groups were homogeneous for age, gender, time since injury, etiology, and ASIA scale. Active rTMS consisted of 15 days of daily sessions of 20 trains of 40 pulses at 20 Hz and an intensity of 90% of resting motor threshold. rTMS was applied with a double cone coil to the leg motor area. RESULTS: There was a significant improvement in LEMS in the active group (28.4 at baseline and 33.2 after stimulation; P = .004) but not in the sham group (29.6 at baseline, and 30.9 after stimulation; P = .6). The active group also showed significant improvements in the MAS, 10MWT, cadence, step length, and TUG, and these improvements were maintained 2 weeks later. Following sham stimulation, significant improvement was found only for step length and TUG. No significant changes were observed in the WISCI II scale in either group. CONCLUSION: High-frequency rTMS over the leg motor area can improve LEMS, spasticity, and gait in patients with motor incomplete SCI.

Referred sensations and neuropathic pain following spinal cord injury.

It has been proposed that painful and non-painful referred sensations (RSs) are associated with reorganization of sensory pathways in patients with complete spinal cord injury (SCI). In order to investigate the referred sensation (RS) phenomenon and its correlation with neuropathic pain (NP) 48 patients with complete SCI, 24 with chronic NP and 24 without pain or paraesthesias were studied using clinical examination and neurophysiological tests. Patients reporting RSs were re-examined at 2 and 10weeks after the first examination. We defined the presence of RS as sensations perceived below the injury level in response to touch and pinprick stimuli in various body points above the injury level. The examination was carried out by one researcher applying the stimuli to the patient under two visual conditions (open and closed eyes), and then asking the patient to make tactile self-stimulation. Seven patients with SCI and NP (29%) reported RS below the injury level. RS were well located and consistently evoked at repeated examinations. Touch and pinprick stimulation elicited similar RS that were non-painful in six patients and painful in one. Visual feedback did not change RS perception and characteristics. None of the patients in the SCI group without NP presented RS. In conclusion, our results indicate that RS is relatively frequent in patients with complete SCI and NP. The common occurrence of RS in patients with NP and the location of the sensations in the same area as NP suggest that pain and RS share common pathophysiological mechanisms.

H reflex modulation by transcranial magnetic stimulation in spinal cord injury subjects after gait training with electromechanical systems.

STUDY DESIGN: Prospective longitudinal study. OBJECTIVES: The aim of this study was to examine the effects of transcranial magnetic stimulation (TMS) on the soleus H reflex in patients with spinal cord injury (SCI) before and after locomotion training. SETTING: Neurorehabilitation hospital in Barcelona, Spain. METHODS: H reflex was elicited in 29 incomplete patients with SCI at 20, 50 and 80 ms after single vertex TMS, and compared with 13 healthy subjects. Patients were subdivided in two groups according to time since injury (<3 months, 3-12 months), and all received training with electromechanical systems. The H reflex modulation pattern to TMS was reassessed and the results were analyzed as a function of change in the patient clinical score. RESULTS: Healthy subjects showed a significant H reflex facilitation at 20 ms (186.1%) and at 80 ms (190.6%) compared with the control H reflex. In patients, the H reflex facilitation at 20 ms was significantly reduced before training (142.5%, P=0.039) compared with healthy subjects. After training, patients with <3 months exhibited an increase in H reflex facilitation at 20 ms (170.7%, P=0.04), a greater gait velocity (P=0.014) and a positive correlation with the walking index for spinal cord injury (WISCI II) scale (P=0.050), compared with those with >3 months. CONCLUSIONS: TMS-induced H reflex modulation may help in the assessment of changes in the descending control of leg reflexes. Our results suggest that the changes on reflex modulation in patients with SCI occur within the first 3 months after injury.

Cutaneous silent periods are not affected by the antihistaminic drug cetirizine.

OBJECTIVE: Noxious digital nerve stimulation leads to transient suppression of the electromyographic activity in isometrically contracted hand muscles, known as the "cutaneous silent period" (CSP). To date, neurotransmitters potentially involved in mediating this electromyographic (EMG) suppression remain unknown. Anecdotal observation lead to the hypothesis that antihistaminic medication may counteract nociceptive EMG suppression, as CSPs in one male subject who was accustomed to CSP recordings were temporarily lost following ingestion of an antihistaminic drug for acute rhinitis. A second otherwise healthy male subject, who was on long-term cetirizine for allergic rhinitis, presented without clearly defined CSPs when volunteering for normal values. METHODS: We undertook a systematic study in five healthy subjects (including the one with temporarily lost CSPs) who underwent serial CSP testing after ingestion of 10 mg cetirizine. CSPs were elicited in thenar muscles following digit II and digit V stimulation (20 times sensory threshold, 100 sweeps rectified and averaged) before and 90, 180, and 360 min following intake of medication. RESULTS: CSP onset latency, CSP end latency and CSP duration, as well as the index of suppression did not change significantly following ingestion of 10 mg cetirizine. Repeat study in the subject with no clearly defined CSPs on long-term treatment revealed persistently absent CSPs after a 5-week withdrawal from cetirizine. CONCLUSION: CSPs are not affected by therapeutic doses of the H1 antihistaminic cetirizine. SIGNIFICANCE: Our findings suggest that histamine plays no major role as a neurotransmitter of CSPs.

The effect of a prepulse stimulus on the EMG rebound following the cutaneous silent period.

The cutaneous silent period (CSP) is a spinal inhibitory reflex mediated by Adelta fibres. The postinhibitory rebound of electromyographic (EMG) activity following the CSP has been mainly attributed to resynchronization of motoneurons, but the possibility of startle reflex activity contributing to the EMG burst has also been suggested. Several types of reflexes may be suppressed by a preceding weak stimulus--a phenomenon called prepulse inhibition (PPI). Our aim was to study whether PPI would diminish the EMG rebound, thereby providing further evidence for excitatory reflex activity contained within the postinhibitory EMG rebound following the CSP. Ten healthy subjects underwent CSP testing following noxious digit II stimulation in two conditions, with and without a prepulse applied to digit III. Rectified surface EMG recordings were obtained from right orbicularis oculi, sternocleidomastoid and thenar muscles of the dominant hand during thumb abduction with 25% of maximum force. The area of the EMG rebound and the EMG reflex responses in orbicularis oculi and sternocleidomastoid were significantly smaller in recordings where a prepulse stimulus was applied 100 ms before the stimulus as compared to control responses without prepulse. CSP onset and end latency, CSP duration, and the degree of EMG suppression were not influenced. Prepulses significantly reduced subjective discomfort as based on visual analog scale scores. Inhibition of the EMG rebound by prepulse stimulation supports the hypothesis that the excitatory EMG activity following the CSP contains not only resynchronization of motoneuronal firing, but also an excitatory reflex component. The most probable type of reflex seems to be a somatosensory startle reflex, a defence reaction which is generated in structures located in the caudal brainstem following an unexpected intense stimulus. Reduction of the discomfort associated with high-intensity electrical fingertip stimulation by a prepulse without affecting CSP parameters underlines the utility of PPI in the context of CSP testing.

Neurophysiologic study of central pain in patients with Parkinson disease.

BACKGROUND: Patients with Parkinson disease (PD) may present with various types of pain. In some instances, no cause can be identified and pain is considered a primary disorder (primary central pain [PCP]). We hypothesized that PCP in patients with PD (PD-PCP) may be due to a dysfunction of pain pathways or the processing of pain inputs in the CNS. METHODS: We carried out a psychophysical and neurophysiologic study in 9 patients with PD-PCP, 9 patients with PD without pain (PD-NoP), and 9 healthy control subjects. We assessed the clinical characteristics of pain, performed quantitative sensory testing with thermal probes, and recorded laser-evoked potentials (LEPs) and laser-induced sudomotor skin responses (1-SSRs) in "off" and "on" conditions. RESULTS: In "off" condition, patients with PD-PCP had lower heat pain and laser pinprick thresholds, higher LEP amplitudes, and less habituation of the l-SSR in comparison with PD-NoP patients and control subjects. Abnormalities were more marked in the most affected side. In "on" condition, psychophysical and neurophysiologic differences disappeared or were significantly attenuated. CONCLUSION: Conduction along peripheral and central pain pathways is normal in patients with Parkinson disease with or without primary central pain. However, apart from signs of hyperalgesia, our patients exhibited lack of habituation of sympathetic sudomotor responses to repetitive pain stimuli, suggesting an abnormal control of the effects of pain inputs on autonomic centers. Abnormalities were attenuated by l-dopa, suggesting that the dysfunction may occur in dopamine-dependent centers regulating both autonomic function and inhibitory modulation of pain inputs.