Rechargeable Internal Neural Stimulators—Is There a Problem with Efficacy?

Introduction: With the advent of rechargeable internal neural stimulators (rINS) for deep brain stimulation, our aim was to survey patient satisfaction and clinical efficacy in an early cohort of patients receiving this new technology. Methods: This is an observational study on nine patients with rINS. All patients had initially received non‐rechargeable INS with established efficacy of their deep brain stimulation system for either dystonia or pain. Patient satisfaction and efficacy with their rINS were established by completion of a questionnaire, a quality of life assessment (SF‐36), and calculation of the total electrical energy delivered (TEED) by the rINS. Results: A reduction in efficacy of their rINS was noticed in 22% of patients. In 78% of patients, there was a problem with recharging their rINS because of poor contact. Two patients (22%) felt that recharging the rINS interfered with their lives and it was a daily reminder that they had a deep brain stimulator system in situ. Eight out of nine patients (89%), however, would recommend to other patients to have an rINS. Conclusion: Most patients were happy with their rechargeable internal neural stimulator. A reduction in efficacy was noticed in 22% of patients, which is similar to the proportion of patients noticing a reduction in efficacy when replacing with a non‐rechargeable system. Thus, all patients require close monitoring post‐replacement of rINS, in case possible adjustment of parameters is required.     

Patient perspectives on the efficacy of a new kind of rechargeable deep brain stimulators1

Purpose/Aim of the study: Rechargeable deep brain stimulation (DBS) system with longer battery life has become available for treating movement disorders. However, little information exists about the safety and management after implantation. Therefore, there is an urgent need to evaluate the recharging performance through long-term observations. Materials and methods: Fifty-three Parkinson's disease (PD) patients were implanted with a new rechargeable device (G102R, PINS Medical). They were observed at the baseline and 3 months, 6 months and 12 months after surgery, with measurement of the acceptance, frequency, recharging time and feeling during recharging. Results: The patients with the ages between 34 and 70 (57.64 ± 7.34) years thought the system was very easy to recharge. The favorite time interval for recharging was 1 week, and 10 days and half a month also chosen. Most of the patients spent around 1 hour recharging, with no unacceptable hot feelings reported. Conclusions: The PD patients could easily and safely recharge this new rechargeable implantable neurostimulators. Thus, these neurostimulators might be an excellent choice for PD patients.     

Patient Perspectives on the Efficacy and Ergonomics of Rechargeable Spinal Cord Stimulators

Objectives: Rechargeable spinal cord stimulation (RSCS) systems have been advocated as a way to reduce replacement surgeries, overall costs, and the morbidity of therapy. However, little data exist as to patients' experiences with these devices, which require more care and maintenance than prior primary cell systems. We analyzed patient experiences with RSCS. Methods: Thirty‐five patients with implanted RSCS systems completed a survey regarding their use of the system, their experiences with recharging, and their perspectives on the device. Results: Patients reported recharging an average of 5.2 times per month for 2.3 hours each time. Overall, 23.3% of recharging attempts were problematic. There was great variability in the length, frequency, and ease of recharging RSCS systems. These factors determined the patients' level of satisfaction. Conclusions: RSCS systems benefit most patients. However, in some patients, the lifestyle costs of recharging may not make RSCS an appropriate means of pain management. Several areas of improvement exist for the design of future devices.     

Brain stimulation: a therapeutic approach for the treatment of neurological disorders

Brain stimulation has become one of the most acceptable therapeutic approaches in recent years and a powerful tool in the remedy against neurological diseases. Brain stimulation is achieved through the application of electric currents using non-invasive as well as invasive techniques. Recent technological advancements have evolved into the development of precise devices with capacity to produce well-controlled and effective brain stimulation. Currently, most used non-invasive techniques are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), whereas the most common invasive technique is deep brain stimulation (DBS). In last decade, application of these brain stimulation techniques has not only exploded but also expanded to wide variety of neurological disorders. Therefore, in the current review, we will provide an overview of the potential of both non-invasive (rTMS and tDCS) and invasive (DBS) brain stimulation techniques in the treatment of such brain diseases.     

Treating the brain at the speed of sound

One of the most important public issues in our rapidly ageing society are brain disorders and neurodegenerative diseases. Effective therapies are limited and therefore costs for public health systems rapidly increase in this sector. However, recently the first clinical evidence for a new class of therapies has emerged - ultrasound for the brain. With the first clinical data on ultrasound brain activation just now published, three fascinating options are available to revolutionize non-invasive brain therapy. All three ultrasound therapies currently receive widespread attention from patients and doctors.     

Therapeutic potential of brain stimulation techniques in the treatment of mental,psychiatric, and cognitive disorders

Treatment for brain diseases has been disappointing because available medications have failed to produce clinical response across all the patients. Many patients either do not respond or show partial and inconsistent effect, and even in patients who respond to the medications have high relapse rates. Brain stimulation has been seen as an alternative and effective remedy. As a result, brain stimulation has become one of the most valuable therapeutic tools for combating against brain diseases. In last decade, studies with the application of brain stimulation techniques not only have grown exponentially but also have expanded to wide range of brain disorders. Brain stimulation involves passing electric currents into the cortical and subcortical area brain cells with the use of noninvasive as well as invasive methods to amend brain functions. Over time, technological advancements have evolved into the development of precise devices; however, at present, most used noninvasive techniques are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), whereas the most common invasive technique is deep brain stimulation (DBS). In the current review, we will provide an overview of the potential of noninvasive (rTMS and tDCS) and invasive (DBS) brain stimulation techniques focusing on the treatment of mental, psychiatric, and cognitive disorders.     

Postural tremor suppression is dependent on thalamic stimulation frequency.

Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) reduces tremor in people with essential tremor (ET), yet the dependence of tremor suppression on stimulation frequency remains unclear. To address this issue, we tested tremor suppression for three 15-second measurements during a variety of stimulation frequencies in 11 ET patients treated with VIM DBS. Stimulation frequencies at or above 100 Hz produced maximal benefit; higher frequencies provided no additional benefit. If this short-term measure predicts long-term response in routine activities at home, then this stimulation frequency setting will prolong battery half-life compared to higher frequency settings. These findings suggest that ET patients treated with VIM DBS may receive adequate benefit from stimulation frequencies about 100 Hz and this setting compared to commonly used higher settings will prolong battery life of surgically implanted pulse generators.     

Reward and detection thresholds for brain stimulation: dissociative effects of cocaine

The effects of cocaine on both rewarding and detection thresholds for intracranial stimulation to the same brain sites in the same animals were determined. The drug caused a dissociation in effects on the two types of brain stimulation. Detection threshold was elevated at doses of cocaine that lowered the reward threshold.     

Chasing Tics in the Human Brain: Development of Open,Scheduled and Closed Loop Responsive Approaches to Deep Brain Stimulation for Tourette Syndrome

Tourette syndrome is a childhood-onset disorder characterized by a combination of motor and vocal tics, often associated with psychiatric comorbidities including attention deficit and hyperactivity disorder and obsessive-compulsive disorder. Despite an onset early in life, half of patients may present symptoms in adulthood, with variable degrees of severity. In select cases, the syndrome may lead to significant physical and social impairment, and a worrisome risk for self injury. Evolving research has provided evidence supporting the idea that the pathophysiology of Tourette syndrome is directly related to a disrupted circuit involving the cortex and subcortical structures, including the basal ganglia, nucleus accumbens, and the amygdala. There has also been a notion that a dysfunctional group of neurons in the putamen contributes to an abnormal facilitation of competing motor responses in basal ganglia structures ultimately underpinning the generation of tics. Surgical therapies for Tourette syndrome have been reserved for a small group of patients not responding to behavioral and pharmacological therapies, and these therapies have been directed at modulating the underlying pathophysiology. Lesion therapy as well as deep brain stimulation has been observed to suppress tics in at least some of these cases. In this article, we will review the clinical aspects of Tourette syndrome, as well as the evolution of surgical approaches and we will discuss the evidence and clinical responses to deep brain stimulation in various brain targets. We will also discuss ongoing research and future directions as well as approaches for open, scheduled and closed loop feedback-driven electrical stimulation for the treatment of Tourette syndrome.     

A pilot trial of square biphasic pulse deep brain stimulation for dystonia: The BIP dystonia study

Background : Dystonia often has inconsistent benefits and requires more energy‐demanding DBS settings. Studies suggest that squared biphasic pulses could provide significant clinical benefit; however, dystonia patients have not been explored. Objectives : To assess safety and tolerability of square biphasic DBS in dystonia patients. Methods : This study included primary generalized or cervical dystonia patients with bilateral GPi DBS. Square biphasic pulses were implemented and patients were assessed at baseline, immediately postwashout, post–30‐minute washout, 1 hour post‐ and 2 hours postinitiation of investigational settings. Results : Ten participants completed the study. There were no patient‐reported or clinician‐observed side effects. There was improvement across time on the Toronto Western Spasmodic Torticollis Rating Scale (χ² = 10.7; P = 0.031). Similar improvement was detected in objective gait measurements. Conclusions : Square biphasic stimulation appears safe and feasible in dystonia patients with GPi DBS. Further studies are needed to evaluate possible effectiveness particularly in cervical and gait features. © 2016 International Parkinson and Movement Disorder Society     

Pallidal deep brain stimulation in the treatment of Meige syndrome

IntroductionMeige syndrome (MS) is characterized by blepharospasm, facial, oromandibular, and often cervical dystonia. The medical treatment of this condition is challenging and unsuccessful over long time. Recent case reports and small clinical series showed that bilateral deep brain stimulation (DBS) of globus pallidus pars interna (GPi) improves dystonic features of MS validated by Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS).Materials and methodsWe report on our experience in using bilateral GPi DBS in 3 cases of MS. We present short-term (3 months) follow-up as well long-term (from 8 months to 36 months) results.Preoperative and postoperative BFMDRS assessments were performed on each patient. The postoperative BFMDRS scores was done when both stimulators were switched on and compared to baseline scores.ResultsBilateral GPi DBS reduced the BFMDRS total movement score by 66% at short-term follow-up, and by 75% at long-term follow-up when compared to baseline scores. The BFMDRS total disability score was reduced by 34% at short-term follow-up, and by 47% at long-term follow-up when compared to baseline scores.ConclusionsOur results showed that bilateral GPi DBS in MS is effective and safe, if conservative treatment options failed. The benefit is not only observed at short-term 3 months period but is maintained at long-term follow-up ranging from 8 to 36 months.     

Formerly known as inhibitory: effects of 1-Hz rTMS on auditory cortex are state-dependent

The major repetitive transcranial magnetic stimulation (rTMS) paradigm applied to the treatment of tinnitus has been the 1-Hz variant due to its alleged inhibitory effects. Clinical effects have, however, been hampered by great interindividual variability as well as the fact that TMS includes no explicit mechanism to modulate excitability in circumscribed regions of tonotopically organised auditory fields. Following studies showing that the effect of TMS depends on the activational state preceding the stimulation, participants were exposed to 10 min of either notch- or bandpass-filtered noise prior to 1-Hz rTMS applied to the left auditory cortex. A control group was additionally assessed using bandpass noise - albeit with subsequent sham stimulation - to assess whether effects were due to the differential sounds alone or to a genuine interaction between sound and rTMS. Electroencephalogram was recorded from 128 electrodes before and after the experimental treatment while participants performed an auditory intensity discrimination task. While state-dependency effects from the behavioural data are not conclusive, several condition × (sound) frequency effects (some specific to the stimulated side) could be observed. Importantly, many of these could not be explained by the use of rTMS or the filtered noise alone. The resulting patterns are, however, complex and temporally variable, which currently prohibits recommendations on how to design a clinically effective approach to treat tinnitus. Nevertheless, our study gives the first evidence that state-dependency principles can induce sound frequency-specific effects in the auditory cortex, providing a crucial proof-of-principle upon which future studies can build.     

High and low frequency electrical stimulation in non-lesional temporal lobe epilepsy

In patients with pharmacologically intractable epilepsy who are not eligible for surgery, deep brain stimulation is currently under evaluation as an alternative treatment. Optimal stimulation parameters, including high (HFS) versus low frequency (LFS) stimulation, are not well defined. Here, we report the effects of HFS (130 pulses per second, pps) and LFS (5pps) of the principal epileptogenic focus, in three patients with non-lesional temporal lobe epilepsy. HFS, but not LFS, was associated with a reduction of the interictal discharges and absence of seizures. HFS may be beneficial in patients with non-lesional temporal lobe epilepsy who are not surgical candidates.     

Improved learning and memory with theta‐burst stimulation of the fornix in rat model of traumatic brain injury

Objective: Learning and memory deficits are a source of considerable morbidity after traumatic brain injury (TBI). We investigated the effect of different patterns of hippocampal stimulation via a fornix electrode on cognitively demanding tasks after TBI. Methods: Male Sprague‐Dawley rats underwent fluid‐percussion injury and were compared with sham‐operated rats. Electrodes were implanted into the fornix and hippocampus, and stimulation of the fornix produced robust evoked potentials in the hippocampus. A 60‐s delayed non‐match‐to‐sample (DNMS) swim T‐maze was serially performed using four stimulation patterns: no stimulation (No Stim), low‐frequency stimulation (LFS, 5 Hz), high‐frequency stimulation (HFS, 130 Hz), and theta‐burst stimulation (TBS, 200 Hz in 50 ms trains, five trains per second; 60 µA biphasic pulses). In a separate cohort of sham and injured animals, Morris water maze (MWM) was performed with or without TBS. Results: In the DNMS swim T‐maze, LFS and HFS did not significantly improve performance after TBI. However, there was a significant difference in performance between TBI + No Stim and TBI + TBS groups (P < 0.05) with no significant difference between Sham + No Stim and TBI + TBS. In the MWM, latency in the TBI + TBS group was significantly different from TBI + No Stim starting on day 2 (P < 0.05) and was not different from Sham + No Stim. The TBI + TBS group performed significantly more platform crossings in the probe trial (P < 0.01) and exhibited improved search strategy starting on day 3 (P < 0.05) compared with TBI + No Stim. Conclusions: Deficits in learning and memory after TBI are improved with TBS of the hippocampus. HFS and LFS do not appear to produce as great an effect as TBS. © 2014 Wiley Periodicals, Inc.     

Functional parallels between the neural and environmental antecedents of aggression

A series of experiments studied the elicitation of biting to electrical brain stimulation in acute squirrel monkey and rat preparations. Stimulation of several neural areas produced biting during stimulation while stimulation at other loci produced biting upon stimulation offset. A second study demonstrated that brain stimulation that produced biting at its offset also could reinforce biting, and here biting could be brought under discriminative environmental stimulus control. Further studies found that partially restrained but intact monkeys and rats would approach and bite inanimate targets during or following brain stimulation. Subsequent experiments demonstrated that unrestrained rats, depending again upon stimulation electrode placement, attacked mice following the offset of reinforcing brain stimulation, and this stimulation offset also produced differential electromyographic activity in masseter versus other muscle groups. Based upon both a literature survey and these findings, it was concluded that the neural mediation of aggressive behavior produced by brain stimulation was congruent with the causal relationships between the onset of aversive and offset of reinforcing antecedent environmental events and aggression.