Mario Meglio

Spinal cord stimulation versus conventional medical management for neuropathic pain: A multicentre randomised controlled trial in patients with failed back surgery syndrome

Abstract Patients with neuropathic pain secondary to failed back surgery syndrome (FBSS) typically experience persistent pain, disability, and reduced quality of life. We hypothesised that spinal cord stimulation (SCS) is an effective therapy in addition to conventional medical management (CMM) in this patient population. We randomised 100 FBSS patients with predominant leg pain of neuropathic radicular origin to receive spinal cord stimulation plus conventional medical management (SCS group) or conventional medical management alone (CMM group) for at least 6 months. The primary outcome was the proportion of patients achieving 50% or more pain relief in the legs. Secondary outcomes were improvement in back and leg pain, health‐related quality of life, functional capacity, use of pain medication and non‐drug pain treatment, level of patient satisfaction, and incidence of complications and adverse effects. Crossover after the 6‐months visit was permitted, and all patients were followed up to 1 year. In the intention‐to‐treat analysis at 6 months, 24 SCS patients (48%) and 4 CMM patients (9%) (p < 0.001) achieved the primary outcome. Compared with the CMM group, the SCS group experienced improved leg and back pain relief, quality of life, and functional capacity, as well as greater treatment satisfaction (p ⩽ 0.05 for all comparisons). Between 6 and 12 months, 5 SCS patients crossed to CMM, and 32 CMM patients crossed to SCS. At 12 months, 27 SCS patients (32%) had experienced device‐related complications. In selected patients with FBSS, SCS provides better pain relief and improves health‐related quality of life and functional capacity compared with CMM alone.

The effects of spinal cord stimulation in neuropathic pain are sustained: a 24-month follow-up of the prospective randomized controlled multicenter trial of the effectiveness of spinal cord stimulation

OBJECTIVEAfter randomizing 100 failed back surgery syndrome patients to receive spinal cord stimulation (SCS) plus conventional medical management (CMM) or CMM alone, the results of the 6-month Prospective Randomized Controlled Multicenter Trial of the Effectiveness of Spinal Cord Stimulation (i.e., PROCESS) showed that SCS offered superior pain relief, health-related quality of life, and functional capacity. Because the rate of crossover favoring SCS beyond 6 months would bias a long-term randomized group comparison, we present all outcomes in patients who continued SCS from randomization to 24 months and, for illustrative purposes, the primary outcome (>50% leg pain relief) per randomization and final treatment. METHODSPatients provided data on pain, quality of life, function, pain medication use, treatment satisfaction, and employment status. Investigators documented adverse events. Data analysis included inferential comparisons and multivariate regression analyses. RESULTSThe 42 patients continuing SCS (of 52 randomized to SCS) reported significantly improved leg pain relief (P < 0.0001), quality of life (P ≤ 0.01), and functional capacity (P = 0.0002); and 13 patients (31%) required a device-related surgical revision. At 24 months, of 46 of 52 patients randomized to SCS and 41 of 48 randomized to CMM who were available, the primary outcome was achieved by 17 (37%) randomized to SCS versus 1 (2%) to CMM (P = 0.003) and by 34 (47%) of 72 patients who received SCS as final treatment versus 1 (7%) of 15 for CMM (P = 0.02). CONCLUSIONAt 24 months of SCS treatment, selected failed back surgery syndrome patients reported sustained pain relief, clinically important improvements in functional capacity and health-related quality of life, and satisfaction with treatment.

Direct demonstration of the effect of lorazepam on the excitability of the human motor cortex.

OBJECTIVES The present study explored the effects of lorazepam, a benzodiazepine with agonist action at the GABA(A) receptor, on human motor cortex excitability as tested using transcranial magnetic stimulation. METHODS We recorded directly the descending volley evoked by single and paired transcranial magnetic stimulation from the spinal cord of a conscious subject with a cervical epidural electrode before and after a single oral dose of lorazepam. We evaluated the effects of lorazepam on the descending volleys evoked by a single magnetic stimulation and paired cortical stimulation using the intracortical inhibition paradigm (subthreshold conditioning stimulus) and the short latency intracortical facilitation paradigm (suprathreshold conditioning stimulus). RESULTS Using a single magnetic stimulus lorazepam decreased the amplitude of the later I waves in the descending volley; this was accompanied by a decrease in the amplitude of the evoked EMG response. Using the intracortical inhibition paradigm lorazepam increased the amount of corticocortical inhibition, particularly at 4 and 5 ms interstimulus intervals. There was no effect on the amount of facilitation observed in the short latency intracortical facilitation paradigm. CONCLUSIONS The present findings provide direct evidence that lorazepam increases the excitability of inhibitory circuits in the human motor cortex.

The physiological basis of the effects of intermittent theta burst stimulation of the human motor cortex

Theta burst stimulation (TBS) is a form of repetitive transcranial magnetic stimulation (TMS). When applied to motor cortex it leads to after‐effects on corticospinal and corticocortical excitability that may reflect LTP/LTD‐like synaptic effects. An inhibitory form of TBS (continuous, cTBS) suppresses MEPs, and spinal epidural recordings show this is due to suppression of the I1 volley evoked by TMS. Here we investigate whether the excitatory form of TBS (intermittent, iTBS) affects the same I‐wave circuitry. We recorded corticospinal volleys evoked by single pulse TMS of the motor cortex before and after iTBS in three conscious patients who had an electrode implanted in the cervical epidural space for the control of pain. As in healthy subjects, iTBS increased MEPs, and this was accompanied by a significant increase in the amplitude of later I‐waves, but not the I1 wave. In two of the patients we tested the excitability of the contralateral cortex and found a significant suppression of the late I‐waves. The extent of the changes varied between the three patients, as did their age. To investigate whether age might be a significant contributor to the variability we examined the effect of iTBS on MEPs in 18 healthy subjects. iTBS facilitated MEPs evoked by TMS of the conditioned hemisphere and suppressed MEPs evoked by stimulation of the contralateral hemisphere. There was a slight but non‐significant decline in MEP facilitation with age, suggesting that interindividual variability was more important than age in explaining our data. In a subgroup of 10 subjects we found that iTBS had no effect on the duration of the ipsilateral silent period suggesting that the reduction in contralateral MEPs was not due to an increase in ongoing transcallosal inhibition. In conclusion, iTBS affects the excitability of excitatory synaptic inputs to pyramidal tract neurones that are recruited by a TMS pulse, both in the stimulated hemisphere and in the contralateral hemisphere. However the circuits affected differ from those influenced by the inhibitory, cTBS, protocol. The implication is that cTBS and iTBS may have different therapeutic targets.

Quality of life, resource consumption and costs of spinal cord stimulation versus conventional medical management in neuropathic pain patients with failed back surgery syndrome (PROCESS trial)

Background: Chronic back and leg pain conditions result in patients’ loss of function, reduced quality of life and increased costs to the society.

Descending spinal cord volleys evoked by transcranial magnetic and electrical stimulation of the motor cortex leg area in conscious humans

1 Descending corticospinal volleys evoked after transcranial magnetic or electrical stimulation of the leg area of the motor cortex were recorded from an electrode in the spinal epidural space of six conscious patients who had electrodes implanted for treatment of chronic pain, and from one anaesthetised patient undergoing surgery for a spinal tumour. 2 At threshold, the shortest‐latency volley (L1 volley) was evoked by stimulation with an anode 2 cm lateral to the vertex. Anodal stimulation at the vertex also elicited a volley at this latency in two patients, but in the other patients the first volley evoked appeared 1—1.3 ms later (L2 volley), at the same latency as the initial volley evoked by magnetic stimulation. High‐intensity stimulation of any type could evoke both the L1 and L2 waves as well as later ones (L3, L4, etc.) that had a periodicity of about 1.5 ms. 3 Voluntary contraction increased the amplitude of the L2 and later volleys, but had no effect on the L1 volley. 4 Intracortical inhibition between pairs of magnetic stimuli resulted in clear suppression of the L4 and later waves. The L2 and L3 waves were unaffected. 5 In the anaesthetised patient the L1 volley occurred 1.7 ms later than the volley produced by transmastoid stimulation of the corticospinal pathways in the brainstem. 6 The L1 volley is likely to be a D wave produced by the direct activation of pyramidal axons in the subcortical white matter; the L2 and later volleys are likely to be I waves produced by the trans‐synaptic activation of corticospinal neurones. The implication is that electrical stimulation with an anode at the vertex is more likely to evoke I waves preferentially than stimulation over the hand area. A more secure way to ensure D wave activation of corticospinal fibres from the leg area is to place the anode 2 cm lateral to the vertex.

Effects of vagus nerve stimulation on cortical excitability in epileptic patients.

Vagus nerve stimulation (VNS) is used as adjunctive treatment for medically refractory epilepsy, but little is known about its mechanisms of action. The effects of VNS on the excitatory and inhibitory circuits of the motor cortex were evaluated in five patients with epilepsy using single- and paired-pulse transcranial magnetic stimulation (TMS). Patients were examined with the stimulator on and off. VNS determined a selective and pronounced increase in the inhibition produced by paired-pulse TMS with no effects on the excitability by single-pulse TMS.

Spinal cord stimulation and cerebral haemodynamics

SummaryAn increase of regional cerebral blood flow (rCBF) has been shown to occur in man during spinal cord stimulation (SCS) by Hosobuchi (1986) and by Meglioet al. (1988) using the 133-Xenon wash-out technique.In this paper we report the effects of SCS on CBF as measured by two different techniques: 8 patients were studied with the 133-Xe method and 28 with the transcranial doppler sonography (TCD), in two cases both studies were performed. The aim of our study was to: 1-verify the effect of SCS on CBF, 2-compare observations made by two different methods, and 3-evaluate a possible correlation between the stimulated spinal segmental level and the modification of CBF. The results of our study confirm that SCS interacts with the mechanisms of regulation of CBF. The stimulation of different spinal cord levels in the same patient can produce different effects and such effects are reproducible. An increase of CBF is more likely to occur with the stimulation of the cervical spinal cord. In patients studied by both methods the sign of CBF changes induced by SCS was the same.Finally, in two patients the effect of SCS on CO2 autoregulation was studied with the TCD. The results of such a study, although preliminary, suggest that CO2 and SCS have a competitive effect upon the mechanisms of regulation of CBF.

Spinal Cord Stimulation (SCS) in the Treatment of Postherpetic Pain

SCS is considered to be of poor value in treating postherpetic pain. We have retrospectively analyzed the results obtained in 10 patients suffering from postherpetic neuralgia. An epidural electrode was implanted, aiming the tip in a position where stimulation could produce paraesthesiae over the painful area. At the end of the test period 6 out of 10 patients reporting a mean analgesia of 52.5% underwent a permanent implant. At mean follow-up (15 months) all the 6 patients were still reporting a satisfactory pain relief (74% of mean analgesia). These figures remained unchanged at the next follow-ups (max 46 months). The result of SCS in our patients, although positive in only 60% of them, are remarkably stable with time. We therefore recommend a percutaneous test trial of SCS in every case of postherpetic neuralgia resistent to medical treatment.

The Psychological Assessment of Candidates for Spinal Cord Stimulation for Chronic Pain Management

Abstract:  It is known that, in spite of meeting appropriate clinical criteria for spinal cord stimulation (SCS) and having undergone flawless procedures, a significant number of patients who fail the therapy continues to exist. It is the purpose of this article to focus on the development of psychosocial indicators of success for SCS, if any. Referring to specialist literature authors present a review of what is known, what is not known, and what remains controversial on this topic. After reading this article we hope the reader will understand the importance of a psychological evaluation as part of the development of standards for identifying appropriate patients for this therapy. To improve treatment outcomes of SCS, seems to be essential to perform psychosocial evaluations on all persons clinically indicated for SCS to exclude those patients, who most probably, on a psychosocial level, will fail the procedure. To maximize treatment efficacy, authors believe spinal cord stimulation for chronic pain control must be part of a comprehensive program. An accurate preoperative psychosocial assessment and a course of psychological assistance both before and after therapy seems to be crucial for improving outcomes.