Cerebellar repetitive transcranial magnetic stimulation (rTMS) for essential tremor: A double-blind,sham-controlled,crossover, add-on clinical trial

BackgroundThere is controversial evidence about the effect of cerebellar low-frequency stimulation in patients with essential tremor (ET).ObjectivesIn this study we assessed safety and effectiveness of 1 Hz (low-frequency) cerebellar repetitive transcranial magnetic stimulation (rTMS) on tremor severity in patients with essential tremor in a sham-controlled crossover trial.MethodsA total of 23 patients assigned into two groups to receive either sham (n = 10) or rTMS (n = 13) treatment, with crossing over after a two-month washout period. Intervention consisted of 900 pulses of 1 Hz rTMS at 90% resting motor threshold or the same protocol of sham stimulation over each cerebellar hemisphere for 5 consecutive days. Tremor severity was assessed by Fahn-Tolosa-Marin (FTM) scale at baseline and at days 5, 12 and 30 after intervention. The FTM consists of 3 subscales including tremor severity rating, performance of motor tasks, and functional disability. Carry-over and treatment effects were analyzed using independent samples t-test.ResultsThere was no significant improvement in the total FTM scores in rTMS compared to the sham stimulation on day 5 (p = 0.132), day 12 (p = 0.574), or day 30 (p = 0.382). Similarly, FTM subscales, including tremor severity rating, motor tasks, and functional disability did not improve significantly after rTMS treatment. Mild headache and local pain were the most frequent adverse events.ConclusionAlthough cerebellar rTMS seems to have acceptable safety when used in ET patients, this study could not prove any efficacy for it in reduction of tremor in these patients. Larger studies are needed to evaluate efficacy of this therapeutic intervention and to provide evidence about the optimal stimulation parameters.     

Higher Pain Sensitivity Predicts Efficacy of a Wearable Transcutaneous Electrical Nerve Stimulation Device for Persons With Fibromyalgia: A Randomized Double-Blind Sham-Controlled Trial

ObjectivesThis study investigated the efficacy of a transcutaneous electrical nerve stimulation (TENS) device (Quell®) for persons with symptoms due to fibromyalgia (FM).Materials and MethodsOne hundred nineteen (N = 119) subjects were randomly assigned to use an active (N = 62) or sham (N = 57) TENS for three months. All subjects completed baseline questionnaires and were administered quantitative sensory testing (QST). Subjects completed the Patients' Global Impression of Change (PGIC, primary outcome measure) and other mailed questionnaires (secondary outcome measures) at six weeks and three months.ResultsThe subjects averaged 50.4 ± 13.5 years of age, 93.3% were female, and 79.8% were Caucasian. Most showed benefit from using the TENS, but no differences between groups were found on the primary outcome measure after three months (active 3.87 ± 1.85, sham 3.73 ± 1.80, 95% confidence interval [CI] [?0.60, 0.88], p = 0.707). Those with more hypersensitivity showed most improvement on the PGIC at six weeks (0.22, 95% CI [0.01, 0.43], p = 0.042) and three months (0.20, 95% CI [0.00, 0.41], p = 0.049) and among those with higher sensitivity based on QST, the active TENS group showed the most benefit with TENS compared with the sham treatment (1.20, 95% CI [0.22, 2.18], p = 0.017). No TENS-related serious adverse events were reported. Subjects in the sham group correctly identified their treatment 87.5% of the time, while, surprisingly, subjects in the active group correctly identified their treatment only 17.4% of the time.ConclusionThis study found no differences between those who were exposed to maximal-frequency active stimulation or minimal-frequency sham stimulation from a wearable TENS in reducing FM-related symptoms. However, those with greater hypersensitivity showed most benefit from TENS. Additional studies to help determine the role individual differences play in the use of TENS in managing FM-related symptoms are needed.     

A Randomized,Sham-Controlled Trial of Repetitive Transcranial Magnetic Stimulation Targeting M1 and S2 in Central Poststroke Pain: A Pilot Trial

ObjectivesCentral poststroke pain (CPSP), a neuropathic pain condition, is difficult to treat. Repetitive transcranial magnetic stimulation (rTMS) targeted to the primary motor cortex (M1) can alleviate the condition, but not all patients respond. We aimed to assess a promising alternative rTMS target, the secondary somatosensory cortex (S2), for CPSP treatment.Materials and MethodsThis prospective, randomized, double-blind, sham-controlled three-arm crossover trial assessed navigated rTMS (nrTMS) targeted to M1 and S2 (10 sessions, 5050 pulses per session at 10 Hz). Participants were evaluated for pain, depression, anxiety, health-related quality of life, upper limb function, and three plasticity-related gene polymorphisms including Dopamine D2 Receptor (DRD2). We monitored pain intensity and interference before and during stimulations and at one month. A conditioned pain modulation test was performed using the cold pressor test. This assessed the efficacy of the descending inhibitory system, which may transmit TMS effects in pain control.ResultsWe prescreened 73 patients, screened 29, and included 21, of whom 17 completed the trial. NrTMS targeted to S2 resulted in long-term (from baseline to one-month follow-up) pain intensity reduction of ≥30% in 18% (3/17) of participants. All stimulations showed a short-term effect on pain (17–20% pain relief), with no difference between M1, S2, or sham stimulations, indicating a strong placebo effect. Only nrTMS targeted to S2 resulted in a significant long-term pain intensity reduction (15% pain relief). The cold pressor test reduced CPSP pain intensity significantly (p = 0.001), indicating functioning descending inhibitory controls. The homozygous DRD2 T/T genotype is associated with the M1 stimulation response.ConclusionsS2 is a promising nrTMS target in the treatment of CPSP. The DRD2 T/T genotype might be a biomarker for M1 nrTMS response, but this needs confirmation from a larger study.     

Percutaneous Neuromodulation of the Brachial Plexus and Sciatic Nerve for the Treatment of Acute Pain Following Surgery: Secondary Outcomes From a Multicenter,Randomized, Controlled Pilot Study

ObjectivesWe recently reported that percutaneous peripheral nerve stimulation (PNS or “neuromodulation”) decreased pain and opioid consumption within the first two weeks following ambulatory surgery. However, the anatomic lead locations were combined for the analysis, and benefits for each location remain unknown. We therefore now report the effects of percutaneous PNS for brachial plexus and sciatic nerve leads separately.Materials and MethodsBefore surgery, leads were implanted percutaneously to target the brachial plexus (N = 21) for rotator cuff repair or sciatic nerve (N = 40) for foot/ankle surgery, followed by a single injection of local anesthetic. Postoperatively, subjects were randomized in a double masked fashion to 14 days of electrical stimulation (N = 30) or sham/placebo (N = 31) using an external pulse generator. The primary outcome of interest was opioid consumption and pain scores evaluated jointly. Thus, stimulation was deemed effective if superior on either outcome and at least noninferior on the other.ResultsFor brachial plexus leads, during the first seven postoperative days pain measured with the numeric rating scale in participants given active stimulation was a median [interquartile range] of 0.8 [0.5, 1.6] versus 3.2 [2.7, 3.5] in patients given sham (p < 0.001). For this same group, opioid consumption in participants given active stimulation was 10 mg [5, 20] versus 71 mg [35, 125] in patients given sham (p = 0.043). For sciatic nerve leads, pain scores for the active treatment group were 0.7 [0, 1.4] versus 2.8 [1.6, 4.6] in patients given sham (p < 0.001). During this same period, participants given active stimulation consumed 5 mg [0, 30] of opioids versus 40 mg [20, 105] in patients given sham (p = 0.004). Treatment effects did not differ statistically between the two locations.ConclusionsAmbulatory percutaneous PNS of both the brachial plexus and sciatic nerve is an effective treatment for acute pain free of systemic side effects following painful orthopedic surgery.