Modulation of the Somatosensory Evoked Potential by Attention and Spinal Cord Stimulation.

Introduction: Spinal Cord Stimulation (SCS) is a last-resort treatment for patients with intractable chronic pain in whom pharmacological and other treatments have failed. Conventional tonic SCS is accompanied by tingling sensations. More recent stimulation protocols like burst SCS are not sensed by the patient while providing similar levels of pain relief. It has been previously reported that conventional tonic SCS can attenuate sensory-discriminative processing in several brain areas, but that burst SCS might have additional effects on the medial, motivational-affective pain system. In this explorative study we assessed the influence of attention on the somatosensory evoked brain responses under conventional tonic SCS as well as burst SCS regime. Methods: Twelve chronic pain patients with an implanted SCS device had 2-weeks evaluation periods with three different SCS settings (conventional tonic SCS, burst SCS, and sham SCS). At the end of each period, an electro-encephalography (EEG) measurement was done, at which patients received transcutaneous electrical pulses at the tibial nerve to induce somatosensory evoked potentials (SEP). SEP data was acquired while patients were attending the applied pulses and while they were mind wandering. The effects of attention as well as SCS regimes on the SEP were analyzed by comparing amplitudes of early and late latencies at the vertex as well as brain activity at full cortical maps. Results: Pain relief obtained by the various SCS settings varied largely among patients. Early SEP responses were not significantly affected by attention nor SCS settings (i.e., burst, tonic, and sham). However, late SEP responses (P300) were reduced with tonic and burst SCS: conventional tonic SCS reduced P300 brain activity in the unattended condition, while burst SCS reduced P300 brain activity in both attended and unattended conditions. Conclusion: Burst spinal cord stimulation for the treatment of chronic pain seems to reduce cortical attention that is or can be directed to somatosensory stimuli to a larger extent than conventional spinal cord stimulation treatment. This is a first step in understanding why in selected chronic pain patients burst SCS is more effective than tonic SCS and how neuroimaging could assist in personalizing SCS treatment.

Effect of Burst Stimulation Evaluated in Patients Familiar With Spinal Cord Stimulation.

OBJECTIVE: Spinal cord stimulation (SCS) is used for treating intractable neuropathic pain. It has been suggested that burst SCS (five pulses at 500 Hz, delivered 40 times per second) suppresses neuropathic pain at least as well as conventional tonic SCS, but without evoking paraesthesia. The efficacy of paraesthesia-free high and low amplitude burst SCS for the treatment of neuropathic pain in patients who are already familiar with tonic SCS was evaluated. MATERIALS AND METHODS: Forty patients receiving conventional (30-120 Hz) tonic SCS for at least six months were included. All patients received high and low amplitude burst SCS, for a two-week period in a double blind randomized crossover design, with a two-week period of tonic stimulation in between. The average visual analogue scale (VAS) scores for pain during the last three days of each stimulation period were evaluated as well as quality of life (QoL) scores, and patient's preferences. RESULTS: Average VAS score for pain were lower during high (40, p = 0.013) and low amplitude burst stimulation (42, p = 0.053) compared with tonic stimulation (52). QoL scores did not differ significantly. At the individual level 58% of the patients experienced significant additional pain reduction (>30% decrease in VAS for pain) during high and/or low amplitude burst stimulation. Eleven patients preferred tonic stimulation, fifteen high, and fourteen low amplitude burst stimulation. CONCLUSION: Burst stimulation is in general more effective than tonic stimulation. Individual patients can highly benefit from burst stimulation; however, the therapeutic range of burst stimulation amplitudes requires individual assessment.

Quality of life increases in patients with painful diabetic neuropathy following treatment with spinal cord stimulation.

PURPOSE: This study aims to explore the changes in pain intensity and quality of life (QoL) experienced by patients with painful diabetic neuropathy (PDN) treated with spinal cord stimulation (SCS) and conventional medical practice (CMP). METHODS: Patient-reported pain intensity and QoL data were obtained from participants in an international multicentre randomised controlled trial comparing SCS versus CMP. Data were collected at randomisation and 6 month follow up by means of a visual analogue scale for pain intensity, the EuroQoL Visual Analogue Scale (EQ VAS) and the EuroQol EQ-5D index. Quality-adjusted life years (QALYs) were calculated for each treatment using the 'area under the curve' method. Differences in QALYs were calculated after adjusting for between-treatment imbalances in baseline QoL. RESULTS: At 6 months, patients allocated to SCS reported larger reductions in pain intensity and improvements in QoL measured by the EQ-5D utility score and EQ VAS as compared to those allocated to CMP. Initial calculations of QALYs for the SCS and CMP groups suggested no statistical differences between the groups. Adjusting for imbalances in baseline EQ-5D scores showed SCS to be associated with significantly higher QALYs compared to CMP. CONCLUSIONS: SCS resulted in significant improvement in pain intensity and QoL in patients with PDN, offering further support for SCS as an effective treatment for patients suffering from PDN. From a methodological point of view, different results would have been obtained if QALY calculations were not adjusted for baseline EQ-5D scores, highlighting the need to account for imbalances in baseline QoL.

Is preoperative pain duration important in spinal cord stimulation? A comparison between tonic and burst stimulation.

OBJECTIVE: Conflicting data have been published as to whether the success rate of spinal cord stimulation (SCS) is inversely proportional to the time interval from the initial onset of symptoms to implantation. Recently, a new stimulation design called burst stimulation has been developed that seems to exert its effect by modulating both the medial and lateral pain pathways and has a better effect than tonic stimulation on global pain, back pain, and limb pain. MATERIALS AND METHODS: We analyzed the effect of preoperative pain duration on the degree of pain suppression by both tonic and burst stimulation in a group of patients (n = 49) who underwent both tonic and burst SCS. RESULTS: Using Pearson correlation analysis and controlling for age and duration of SCS, no correlation could be found between the preoperative pain duration and the success of SCS, either for tonic or for burst SCS, as defined by a numeric rating scale for pain. Using a different analysis method, dividing patients into groups according to preoperative pain duration, the same absence of influence was found. Pain was better suppressed by burst stimulation than tonic stimulation, irrespective of the preoperative pain duration. CONCLUSIONS: These results suggest that the duration of pain is not an exclusion criterion for SCS and that similar success rates can be obtained for longstanding pain and pain of more recent onset.

A 2-center comparative study on tonic versus burst spinal cord stimulation: amount of responders and amount of pain suppression.

INTRODUCTION: Spinal cord stimulation is a safe and effective procedure applied for medically intractable neuropathic pain and failed back surgery syndrome. Recently, a novel stimulation paradigm was developed, called burst stimulation consisting of intermittent packets of closely spaced high-frequency stimuli. The design consists of 40 Hz burst mode with 5 spikes at 500 Hz per burst, with a pulse width of 1 ms and 1 ms interspike interval delivered in constant current mode. METHODS AND MATERIALS: A retrospective analysis is performed looking at 102 patients from 2 neuromodulation centers, 1 in Belgium and 1 in the Netherlands. This consisted of 2 groups, 1 group who had become failures to tonic (conventional) stimulation and 1 group who still responded to tonic stimulation. All patients were switched from tonic to burst stimulation and the amount of responders as well as the amount of pain suppression was assessed. RESULTS: Overall burst stimulation was significantly better than tonic stimulation and baseline. On average the pain on numeric rating scale (NRS) improved from 7.8 at baseline to 4.9 with tonic to 3.2 with burst stimulation. For the Belgian and Dutch centers combined, 62.5% of nonresponders to tonic stimulation did respond to burst stimulation, on average, with 43% pain suppression. Most responders to tonic further improved with burst stimulation; on average, pain suppression improved from 50.6% to 73.6.3%. The results (from both centers) did not differ for the amount of obtained pain suppression, only for the amount of responders, which could be related to the different profile of the 2 participating centers. CONCLUSIONS: Burst seems to be significantly better than tonic stimulation. It can rescue an important amount of nonresponders to tonic stimulation and can further improve pain suppression in responders to tonic stimulation.

Spinal cord stimulation in patients with painful diabetic neuropathy: a multicentre randomized clinical trial.

Painful diabetic neuropathy (PDN) is a peripheral neuropathic pain condition that is often difficult to relieve. Spinal cord stimulation (SCS) is a proven effective therapy for various types of mixed neuropathic conditions, yet effectiveness of SCS treatment for PDN is not well established. To our knowledge, ours is the first multicentre randomized controlled trial investigating the effectiveness of SCS in patients with PDN. Sixty patients with PDN in the lower extremities refractory to conventional medical therapy were enrolled and followed for 6 months. They were randomized 2:1 to best conventional medical practice with (SCS group) or without (control group) additional SCS therapy, and both groups were assessed at regular intervals. At each follow-up visit, the EuroQoL 5D, the short form McGill Pain Questionnaire (SF-MPQ) and a visual analogue scale (VAS, ranging 0-100) to measure pain intensity were recorded. The average VAS score for pain intensity was 73 in the SCS group and 67 in the control group at baseline. After 6 months of treatment, the average VAS score was significantly reduced to 31 in the SCS group (P<.001) and remained 67 (P=.97) in the control group. The SF-MPQ and EuroQoL 5D questionnaires also showed that patients in the SCS group, unlike those in the control group, experienced reduced pain and improved health and quality of life after 6 months of treatment. In patients with refractory painful diabetic neuropathy, spinal cord stimulation therapy significantly reduced pain and improved quality of life.

Burst spinal cord stimulation evaluated in patients with failed back surgery syndrome and painful diabetic neuropathy.

OBJECTIVE: Spinal cord stimulation (SCS) is used for treating intractable neuropathic pain. Generally, it induces paresthesia in the area covered by SCS. Burst SCS was introduced as a new stimulation paradigm with good pain relief without causing paresthesia. Good results have been obtained in patients who were naive to SCS. In this study we assess the effectiveness of burst stimulation in three groups of chronic pain patients who are already familiar with SCS and the accompanying paresthesia. METHODS: Forty-eight patients with at least six months of conventional, tonic stimulation tested burst stimulation for a period of two weeks. They were classified in three different groups: a cross-section of our population with painful diabetic neuropathy (PDN), a cross-section of our population with failed back surgery syndrome (FBSS), and FBSS patients who over time had become poor responders (PR) to SCS. Visual analog scale scores for pain were assessed prior to implantation, with tonic stimulation, and after two weeks of burst stimulation. RESULTS: Burst stimulation reduced pain significantly for almost all patients. When compared with tonic stimulation, burst stimulation led to a significant additional pain reduction of on average 44% in patients with PDN (p < 0.001) and 28% in patients with FBSS (p < 0.01). Patients from the PR group benefitted less from burst stimulation on average. In addition, burst stimulation caused little or no paresthesia whereas tonic stimulation did induce paresthesia. Most patients preferred burst stimulation, but several preferred tonic stimulation because the paresthesia assured them that the SCS was working. CONCLUSION: About 60% of the patients with tonic SCS experienced further pain reduction upon application of burst stimulation.

Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson's disease (NSTAPS study): a randomised controlled trial.

BACKGROUND: Patients with advanced Parkinson's disease often have rapid swings between mobility and immobility, and many respond unsatisfactorily to adjustments in pharmacological treatment. We assessed whether globus pallidus pars interna (GPi) deep brain stimulation (DBS) gives greater functional improvement than does subthalamic nucleus (STN) DBS. METHODS: We recruited patients from five centres in the Netherlands who were aged 18 years or older, had idiopathic Parkinson's disease, and had, despite optimum pharmacological treatment, at least one of the following symptoms: severe response fluctuations, dyskinesias, painful dystonias, or bradykinesia. By use of a computer-generated randomisation sequence, we randomly assigned patients to receive either GPi DBS or STN DBS (1:1), applying a minimisation procedure according to drug use (levodopa equivalent dose <1000 mg vs ≥1000 mg) and treatment centre. Patients and study assessors (but not those who assessed adverse events) were masked to treatment allocation. We had two primary outcomes: functional health as measured by the weighted Academic Medical Center Linear Disability Scale (ALDS; weighted by time spent in the off phase and on phase) and a composite score for cognitive, mood, and behavioural effects up to 1 year after surgery. Secondary outcomes were symptom scales, activities of daily living scales, a quality-of-life questionnaire, the occurrence of adverse events, and drug use. We used the intention-to-treat principle for all analyses. This trial is registered with www.controlled-trials.com, number ISRCTN85542074. FINDINGS: Between Feb 1, 2007, and March 29, 2011, we enrolled 128 patients, assigning 65 to GPi DBS and 63 to STN DBS. We found no statistically significant difference in either of our primary outcomes: mean change in weighted ALDS (3·0 [SD 14·5] in the GPi group vs 7·7 [23·2] in the STN group; p=0·28) and the number of patients with cognitive, mood, and behavioural side-effects (36 [58%] of 62 patients in the GPi group vs 35 [56%] of 63 patients in the STN group; p=0·94). Secondary outcomes showed larger improvements in off-drug phase in the STN group compared with the GPi group in the mean change in unified Parkinson's disease rating scale motor examination scores (20·3 [16·3] vs 11·4 [16·1]; p=0·03), the mean change in ALDS scores (20·3 [27·1] vs 11·8 [18·9]; p=0·04), and medication (mean levodopa equivalent drug reduction: 546 [SD 561] vs 208 [521]; p=0·01). We recorded no difference in the occurrence of adverse events between the two groups. Other secondary endpoints showed no difference between the groups. INTERPRETATION: Although there was no difference in our primary outcomes, our findings suggest that STN could be the preferred target for DBS in patients with advanced Parkinson's disease. FUNDING: Stichting Internationaal Parkinson Fonds, Prinses Beatrix Fonds, and Parkinson Vereniging.

Spinal cord stimulation with hybrid lead relieves pain in low back and legs.

OBJECTIVE: The failed back surgery syndrome (FBSS) is the most common chronic pain syndrome. Whereas it is relatively easy to achieve pain relief in the lower limbs of FBSS patients with spinal cord stimulation (SCS), it is difficult to manage low back pain with SCS. The performance of a paddle-shaped SCS lead that can be inserted surgically as well as percutaneously (a hybrid lead) was evaluated in a prospective study on the relief of low back pain and leg pain in patients with FBSS. MATERIALS AND METHODS: Patients with FBSS being eligible for SCS were enrolled in the study, and a hybrid lead was placed surgically. Outcome measures included pain scores for low back and leg pain assessed by visual analog scale (VAS), pain medication, and patient satisfaction. These scores were assessed before and at regular intervals after implantation. RESULTS: It was shown that a single hybrid lead, generally positioned over the physiological midline of the spinal cord, is capable of alleviating both low back and leg pain in patients with FBSS. Forty-five subjects were eligible for SCS and received trial stimulation. Forty-two of them had a successful trial period and were converted to a permanent system. Their average VAS score at baseline was 8.0 for lower limb pain and 7.5 for low back pain. After six months of SCS, these average VAS scores were reduced to 3.2 and 3.5, respectively, and also pain medication was reduced significantly. CONCLUSION: SCS with a hybrid lead in subjects with FBSS is safe, and causes significant pain relief in both the low back and the lower limbs.

Two cases of autosomal recessive generalized dystonia in childhood: 5 year follow-up and bilateral globus pallidus stimulation results.

We report two brothers with an unknown form of early-onset familiar dystonia. Characteristic clinical features are (1) childhood-onset; (2) extrapyramidal motor symptoms; (3) dysarthria; and (4) mental retardation. Additional findings include loss of D(2)-receptors in both basal ganglia and hypoplasia of the cerebellar vermis with dilatation of the fourth ventricle and cisterna magna. There seems to be a progressive and non-progressive form of this clinical entity. Dystonic symptoms of the progressive form that occurred in one of the brothers were alleviated dramatically by bilateral internal globus pallidus (Gpi) stimulation, and the improvement has lasted now for 5 years.

A quick and universal method for stereotactic visualization of the subthalamic nucleus before and after implantation of deep brain stimulation electrodes.

For deep brain stimulation (DBS) of the subthalamic nucleus (STN), it would be an advantage if the STN could be visualized with fast acquisition of MR images, allowing direct and individual targeting. We present a protocol for T2-weighted, nonvolumetric fast-acquisition MRI, implemented at 8 centers in 6 countries. Acquisition time varied between 3 min 5 s and 7 min 48 s according to the center, and imaging often provided visualization of the STN on axial and coronal scans. Postoperatively, the same imaging protocol permitted visualization of the target area and DBS electrodes with minimum artifacts. This imaging technique may contribute to a decrease in the number of electrode passes at surgery.