Implant for Augmentation of Cerebral Blood Flow Trial-1 (ImpACT-1). A single-arm feasibility study evaluating the safety and potential benefit of the Ischemic Stroke System for treatment of acute ischemic stroke.

BACKGROUND: The Ischemic Stroke System is a novel device designed to deliver stimulation to the sphenopalatine ganglion(SPG).The SPG sends parasympathetic innervations to the anterior cerebral circulation. In rat stroke models, SPG stimulation results in increased cerebral blood flow, reduced infarct volume, protects the blood brain barrier, and improved neurological outcome. We present here the results of a prospective, multinational, single-arm, feasibility study designed to assess the safety, tolerability, and potential benefit of SPG stimulation inpatients with acute ischemic stroke(AIS). METHODS: Patients with anterior AIS, baseline NIHSS 7-20 and ability to initiate treatment within 24h from stroke onset, were implanted and treated with the SPG stimulation. Patients were followed up for 90 days. Effect was assessed by comparing the patient outcome to a matched population from the NINDS rt-PA trial placebo patients. RESULTS: Ninety-eight patients were enrolled (mean age 57years, mean baseline NIHSS 12 and mean treatment time from stroke onset 19h). The observed mortality rate(12.2%), serious adverse events (SAE)incidence(23.5%) and nature of SAE were within the expected range for the population. The modified intention to treat cohort consisted of 84 patients who were compared to matched patients from the NINDS placebo arm. Patients treated with SPG stimulation had an average mRS lower by 0.76 than the historical controls(CMH test p = 0.001). CONCLUSION: The implantation procedure and the SPG stimulation, initiated within 24hr from stroke onset, are feasible, safe, and tolerable. The results call for a follow-up randomized trial (funded by BrainsGate; clinicaltrials.gov number, NCT03733236).

An injectable implant to stimulate the sphenopalatine ganglion for treatment of acute ischaemic stroke up to 24 h from onset (ImpACT-24B): an international, randomised, double-blind, sham-controlled, pivotal trial.

BACKGROUND: Sphenopalatine ganglion stimulation increased cerebral collateral blood flow, stabilised the blood-brain barrier, and reduced infarct size, in preclinical models of acute ischaemic stroke, and showed potential benefit in a pilot randomised trial in humans. The pivotal ImpACT-24B trial aimed to determine whether sphenopalatine ganglion stimulation 8-24 h after acute ischaemic stroke improved functional outcome. METHODS: ImpACT-24B is a randomised, double-blind, sham-controlled, pivotal trial done at 73 centres in 18 countries. It included patients (men aged 40-80 years and women aged 40-85 years) with anterior-circulation acute ischaemic stroke, not undergoing reperfusion therapy. Enrolled patients were randomly assigned via web-based randomisation to receive active sphenopalatine ganglion stimulation (intervention group) or sham stimulation (sham-control group) 8-24 h after stroke onset. Patients, clinical care providers, and all outcome assessors were masked to treatment allocation. The primary efficacy endpoint was the difference between active and sham groups in the proportion of patients whose 3-month level of disability improved above expectations. This endpoint was evaluated in the modified intention-to-treat (mITT) population (defined as all patients who received one active or sham treatment session) and the population with confirmed cortical involvement (CCI) and was analysed using the Hochberg multi-step procedure (significance in both populations if p<0·05 in both, and in one population if p<0·025 in that one). Safety endpoints at 3 months were all serious adverse events (SAEs), SAEs related to implant placement or removal, SAEs related to stimulation, neurological deterioration, and mortality. All patients who underwent an attempted sphenopalatine ganglion stimulator or sham stimulator placement procedure were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT00826059. FINDINGS: Between June 10, 2011, and March 7, 2018, 1078 patients were enrolled and randomly assigned to either the intervention or the sham-control group. 1000 patients received at least one session of sphenopalatine ganglion stimulation or sham stimulation and entered the mITT population (481 [48%] received sphenopalatine ganglion stimulation, 519 [52%] were sham controls), among whom 520 (52%) patients had CCI on imaging. The proportion of patients in the mITT population whose 3-month disability level was better than expected was 49% (234/481) in the intervention group versus 45% (236/519) in the sham-control group (odds ratio 1·14, 95% CI 0·89-1·46; p=0·31). In the CCI population, the proportion was 50% (121/244) in the intervention group versus 40% (110/276) in the sham-control group (1·48, 1·05-2·10; p=0·0258). There was an inverse U-shaped dose-response relationship between attained sphenopalatine ganglion stimulation intensity and the primary outcome in the CCI population: the proportion with favourable outcome increased from 40% to 70% at low-midrange intensity and decreased back to 40% at high intensity stimulation (p=0·0034). There were no differences in mortality or SAEs between the intervention group (n=536) and the sham-control group (n=519) in the safety population. INTERPRETATION: Sphenopalatine ganglion stimulation is safe for patients with acute ischaemic stroke 8-24 h after onset, who are ineligible for thrombolytic therapy. Although not reaching significance, the trial's results support that, among patients with imaging evidence of cortical involvement at presentation, sphenopalatine ganglion stimulation is likely to improve functional outcome. FUNDING: BrainsGate Ltd.

Cluster headache: crosspoint between otologists and neurologists-treatment of the sphenopalatine ganglion and systematic review.

Among cephalgias, cluster headache (CH) is the rarest and the most disabling, explaining the appellation of "suicide headache." Up to 20% of chronic CH reveals to be resistant to pharmacological treatments, in which case interventional procedures should be considered. Many reports evaluated invasive approaches and a wide strand of research is dedicated to the sphenopalatine ganglion. Our paper will now be focused on providing an overview on modern applications on the sphenopalatine ganglion (SPG), their outcomes, and their feasibility in terms of risks and benefits. The group reviewed the international literature systematically for procedures targeting the sphenopalatine ganglion and its branches for episodic and chronic CH, including block, stimulation, radiofrequency, stereotactic radiosurgery, and vidian neurectomy. Seventeen articles fixed our inclusion criteria. Comparing the outcomes that have been analyzed, it is possible to notice how the most successful procedure for the treatment of refractory chronic and episodic CH is the SPG block, which reaches respectively 76.5% and 87% of efficacy. Radiofrequency has a wide range of outcomes, from 33 to 70.3% in CCH. Stimulation of SPG only achieved up to 55% of outcomes in significant reduction in attack frequency in CCH and 71% in ECH. Radiosurgery and vidian neurectomy on SPG have also been analyzed. Generally, ECH patients show better response to standard medical therapies; nevertheless, even this more manageable condition may sometimes benefit from interventional therapies mostly reserved for CCH. First results seem promising and considering the low frequency of side effects or complications, we should think of expanding the indications of the procedures also to those conditions. Outcomes certainly suggest that further studies are necessary in order to understand which method is the most effective and with less side effects. Placebo-controlled studies would be pivotal, and tight collaboration between neurologists and otorhinolaryngologists should also be central in order to give correct indications, which allow us to expect procedures on the SPG to be an effective and mostly safe method to control either refractory ECH or CCH.

Novel Interventional Nonopioid Therapies in Headache Management.

PURPOSE OF REVIEW: Headaches encompass a broad-based category of a symptom of pain in the region of the head or neck. For those patients who unfortunately do not obtain relief from conservative treatment, interventional techniques have been developed and are continuing to be refined in an attempt to treat this subset of patients with the goal of return of daily activities. This investigation reviews various categories of headaches, their pathophysiology, and types of interventional treatments currently available. RECENT FINDINGS: Injection of botulinum toxin has been shown to increase the number of headache free days for patients suffering from chronic tension-type headaches. Suboccipital steroid injection has been demonstrated as a successful treatment option for patients suffering from cluster headache. Occipital nerve stimulation (ONS) has been described as a treatment for all types of trigeminal autonomic cephalgias. Percutaneous ONS is a minimally invasive and reversible approach to manage occipital neuralgia performed utilizing subcutaneous electrodes placed superficial to the cervical muscular fascia in the suboccipital area. Radiofrequency lesioning is another commonly used treatment in the management of chronic pain syndromes of the head and neck. If a diagnostic sphenopalatine ganglion block successfully resolves the patient's symptoms, neurolysis can be employed as a more permanent solution. Although many patients who suffer from headaches can be treated with conservative, less-invasive treatments, there still remains at present an ever-increasing need for those patients who are refractory to conservative measures and thus require interventional treatments. These procedures are continually evolving to become safer, more precise, and more readily available for clinicians to provide to their patients.

Sphenopalatine Ganglion (SPG): Stimulation Mechanism, Safety, and Efficacy.

OBJECTIVE: To describe the history of and available data on sphenopalatine ganglion (SPG) neuromodulation in the treatment of headache up to the present. BACKGROUND: The SPG has been a therapeutic target to treat primary headache disorders for over 100 years. Multiple destructive lesions have also been tried with variable rate and duration of success. Neurostimulation of the SPG for cluster headache was first described in 2007. METHODS: This is not a systematic review. The authors review the anatomy and pathophysiology of the SPG and cluster headache and the important clinical trials, relating a history of how SPG neuromodulation reached the current state of approval in the European Union (EU) and pivotal registration study for cluster headache in the US. RESULTS: The EU approved SPG stimulation for cluster headache with a CE Mark in February of 2012. Since then, several EU countries have elected to reimburse implantation for cluster headache, and over 300 patients have been implanted worldwide. CONCLUSIONS: Success rates for implanted SPG neuromodulation in the experimental phase of the European randomized controlled trial, in the open label extension trial, and in the registry of patients implanted outside of the trial remain at about two-thirds of patients implanted being responders, defined as being able to terminate at least 50% of attacks or having at least a 50% decrease in attack frequency or both. A US pivotal registration study is underway to confirm these results and obtain FDA approval for this treatment for cluster headache patients. Further studies in migraine are also underway.

Integrity of the Ganglionated Plexi Is Essential to Parasympathetic Innervation of the Atrioventricular Node by the Right Vagus Nerve.

INTRODUCTION: Radiofrequency isolation of pulmonary vein can be accompanied by transient sinus bradycardia or atrioventricular nodal (AVN) block, suggesting an influence on vagal cardiac innervation. However, the importance of the atrial fat pads in relation with the vagal innervation of AVN in humans remains largely unknown. The aim of this study was to evaluate the role of ganglionated plexi (GP) in the innervation of the AVN by the right vagus nerve. METHODS AND RESULTS: Direct epicardial high-frequency stimulation (HFS) of the GP (20 patients) and the right vagus nerve (10 patients) was performed before and after fat pad exclusion or destruction in 20 patients undergoing thoracoscopic epicardial ablation for the treatment of persistent AF. Asystole longer than 3 seconds or acute R-R prolongation over 25% was considered as a positive response to HFS. Prior to the ablation, positive responses to HFS were detected in 3 GPs in 7 patients (35%), 2 GPs in 5 patients (25%), and one GP in 8 patients (40%). After exclusion of the fat pads, all patients had a negative response to HFS. All the patients who exhibited a positive response to right vagus nerve stimulation (n = 10) demonstrated negative responses after the ablation. CONCLUSION: The integrity of the GP is essential for the right vagus nerve to exert physiological effects of on AVN in humans.

"Cardio-Neuromodulation" With a Multielectrode Irrigated Catheter: A Potential New Approach for Patients With Cardio-Inhibitory Syncope.

Syncope is frequently neurally mediated and can seriously affect quality of life. Different ablation strategies have been successfully performed. These approaches have not gained wide acceptance and are quite extensive and complex, exposing patients to significant risks. This article reports the case of a 16-year-old girl who was severely affected by frequent and prolonged episodes of syncope and was treated by tailored ablation of the anterior right ganglionated plexus with a multielectrode irrigated catheter. She had fainted >30 times in the 5 years preceding treatment, experiencing approximately 10 severe episodes of syncope in the previous 12 months. After 3 minutes of ablation, the P-P interval was reduced by >400 milliseconds. Syncope disappeared and the patient has remained completely asymptomatic over a follow-up of 22 months. The "reset" basal P-P interval has remained unchanged (follow-up electrocardiogram at 16 months). At 6 months, there was no residual heart rate activity <50 bpm. On 24-hour rhythm registration, P-P intervals ≥1,000 milliseconds (corresponding to a heart rate of ≤60 bpm) were reduced by >16,000 beats. We believe that this case report is original for several reasons: the unusual clinical presentation; the unique structure targeted; the very limited ablation, implying much lower risks for the patient; the anatomical approach; and the different endpoint. This new "cardio-neuromodulation" approach could be useful for the treatment of patients with neurally mediated syncope.

Current Approaches to Neuromodulation in Primary Headaches: Focus on Vagal Nerve and Sphenopalatine Ganglion Stimulation.

Neuromodulation is a promising, novel approach for the treatment of primary headache disorders. Neuromodulation offers a new dimension in the treatment that is both easily reversible and tends to be very well tolerated. The autonomic nervous system is a logical target given the neurobiology of common primary headache disorders, such as migraine and the trigeminal autonomic cephalalgias (TACs). This article will review new encouraging results of studies from the most recent literature on neuromodulation as acute and preventive treatment in primary headache disorders, and cover some possible underlying mechanisms. We will especially focus on vagus nerve stimulation (VNS) and sphenopalatine ganglion (SPG) since they have targeted autonomic pathways that are cranial and can modulate relevant pathophysiological mechanisms. The initial data suggests these approaches will find an important role in headache disorder management going forward.

Sphenopalatine ganglion stimulation in cluster headache and other types of headache.

Objectives The cluster headache is the most excruciatingly painful primary headache. In some patients, neither preventive treatment nor acute treatment is effective or treatment is poorly tolerated. The sphenopalatine ganglion (SPG) has an important role in the pathophysiology of cluster headache and, for this reason, SPG stimulation has been used to treat cluster headache. Methods We have reviewed the published literature on the role of the SPG in cluster headache and the use of different treatments targeting the SPG. Results Multiple procedures have been used over the SPG to treat pain and trigemino-autonomic symptoms in patients with refractory cluster headache. After obtaining good results in a small number of patients, a miniaturized stimulator was developed. Stimulation of the SPG with this device proved to be efficacious in acute and preventive treatment in a clinical trial involving patients with chronic refractory cluster headache. Implantation of the device is minimally invasive and the most frequent side-effects are mild, such as paraesthesia and pain over the maxillary area. In patients who have used the SPG device for longer than one year, the therapeutic effect remains effective and the side-effects decrease. Conclusions The reported studies have demonstrated that SPG stimulation is a safe and effective treatment for chronic cluster headache. Long-term studies have shown that the effect remains over time and this treatment could be a good choice in patients with chronic refractory headache. We need more data about its potential use in other forms of headache, such as other trigemino-autonomic headaches or migraine.

Technical and surgical aspects of the sphenopalatine ganglion (SPG) microstimulator insertion procedure.

Cluster headache (CH) is a debilitating, severe form of headache. A novel non-systemic therapy has been developed that produces therapeutic electrical stimulation to the sphenopalatine ganglion (SPG). A transoral surgical technique for inserting the Pulsante SPG Microstimulator into the pterygopalatine fossa (PPF) is presented herein. Technical aspects include detailed descriptions of the preoperative planning using computed tomography or cone beam computed tomography scans for presurgical digital microstimulator insertion into the patient-specific anatomy and intraoperative verification of microstimulator placement. Surgical aspects include techniques to insert the microstimulator into the proper midface location atraumatically. During the Pathway CH-1 and Pathway R-1 studies, 99 CH patients received an SPG microstimulator. Ninety-six had a microstimulator placed within the PPF during their initial procedure. Perioperative surgical sequelae included sensory disturbances, pain, and swelling. Follow-up procedures included placement of a second microstimulator on the opposite side (n=2), adjustment of the microstimulator lead location (n=13), re-placement after initial unsuccessful placement (n=1), and removal (n=5). This SPG microstimulator insertion procedure has sequelae comparable to other oral cavity procedures including tooth extractions, sinus surgery, and dental implant placement. Twenty-five of 29 subjects (86%) completing a self-assessment questionnaire indicated that the surgical effects were tolerable and 90% would make the same decision again.

Sphenopalatine ganglion stimulation with one acupuncture needle for moderate-severe persistent allergic rhinitis: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Allergic rhinitis is a symptomatic allergic disease of the nose that affects 10 to 20% of the global population. Chinese otolaryngologists use one acupuncture needle to stimulate the sphenopalatine ganglion because of its potential advantages for treating moderate-severe persistent allergic rhinitis compared with traditional Chinese acupuncture (verum acupuncture); however, little evidence is available to support the wide clinical use thus far. Therefore, we propose a protocol for a parallel, multicenter, assessor-blinded, randomized controlled trial to evaluate sphenopalatine ganglion stimulation with one acupuncture needle compared to verum acupuncture for treatment of moderate-severe persistent allergic rhinitis. METHODS: In the trial, 96 patients previously diagnosed with moderate-severe persistent allergic rhinitis and meeting all inclusion criteria will be allocated to one of two equal therapeutic groups by using a computer-generated randomization list. The interventional group will receive sphenopalatine ganglion stimulation with one acupuncture needle for 4 weeks (once or twice weekly, total four to eight sessions); attending physicians will decide whether the second session is required in a week by examining signs and symptoms. The control group will receive individualized verum acupuncture for 4 weeks (twice weekly, total eight sessions). Follow-up evaluations will be performed 1 month later. The primary outcome measure is the change in the total nasal symptom score from the baseline to week 4. The secondary outcome measures include onset time and duration of effectiveness in every session, change in number of days with moderate-severe persistent allergic rhinitis from the baseline to week 8, change in total immunoglobulin E level and eosinophil count in venous blood from the baseline to week 4, change in Rhinoconjunctivitis Quality of Life Questionnaire score from the baseline to week 4, and clinical waiting time. DISCUSSION: The trial should provide evidence for the benefits of sphenopalatine ganglion stimulation with one acupuncture needle for treating moderate-severe persistent allergic rhinitis, including better change in total nasal symptom score, faster onset time, longer duration of effectiveness, and shorter treatment time. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN21980724 (registered on 27 March 2014).

Role of sphenopalatine ganglion stimulation in cluster headache.

Cluster headache attacks are characterized by extreme unilateral pain mostly in the first trigeminal branch and an ipsilateral activation of the cranial parasympathetic system, pointing to a relevant role of the cranial parasympathetic system in the pathophysiology, and therapy of cluster headache. Based on animal experiments and several interventions of the sphenopalatine ganglion (such as an aesthetic or alcoholic blocks and radiofrequency ablation) in cluster headache patients, stimulation of the sphenopalatine ganglion (SPGS) as the major efferent peripheral parasympathetic structure was established with an encouraging abortive effect on acute attacks and a frequency reduction over time. In this review, the clinical data and potentially underlying pathophysiological concepts of SPGS are discussed in detail, which in brief point to a relevant role of the parasympathetic system both in the induction and termination of attacks.

Ablation of epicardial ganglionated plexi increases atrial vulnerability to arrhythmias in dogs.

BACKGROUND: Previous studies have suggested that systematic ablation of ganglionated plexi (GP) could increase the short-term success rate of radiofrequency ablation for atrial fibrillation, but the long-term efficacy of this approach is not fully established. METHODS AND RESULTS: Twenty-four mongrel dogs were divided into 3 groups: epicardial GP ablation group 1 (n=8), epicardial GP ablation group 2 (n=8), and a sham operation group (n=8). In the 2 epicardial GP ablation groups, the 4 major GP and the ligament of Marshall were systematically ablated. The effective refractory period and inducibility of tachyarrhythmias were measured before and immediately after GP ablation in epicardial GP ablation group 1 and 8 weeks later in the other 2 groups. Tyrosine hydroxylase and choline acetyltransferase expressions were also determined immunohistochemically 8 weeks later in the latter groups. Compared with epicardial GP ablation group 1 and the sham operation group, epicardial GP ablation group 2 had the shortest atrial and ventricular effective refractory period and the highest inducibility of atrial tachyarrhythmias. The inducibility of ventricular tachyarrhythmias among the 3 groups was comparable. The density of tyrosine hydroxylase- and choline acetyltransferase-positive nerves in the atrium was the highest in epicardial GP group 2, whereas there were no significant intergroup differences in the densities of these 2 types of nerves in the ventricle. CONCLUSIONS: After 8 weeks of healing, epicardial GP ablation without additional atrial ablation was potentially proarrhythmic, which may be attributable to decreased atrial effective refractory period and hyper-reinnervation involving both sympathetic and parasympathetic nerves.

Neurostimulation at pterygopalatine fossa for cluster headaches and cerebrovascular disorders.

There are numerous neural structures (parasympathetic, sympathetic, and trigeminal sensory) that are compacted in a small well defined area of the pterygopalatine fossa (PPF). These targets can be readily accessed via minimally invasive neuromodulation techniques making the methods more desirable than neurosurgical deep brain or hypothalamic intervention. Recent research has shed light over the important role of the sphenopalatine ganglion (SPG), which is located within the PPF, in cerebrovascular autonomic physiology as well as in the pathophysiology of different headache disorders (cluster headache, migraine, and trigeminal autonomic cephalalgias). Accordingly, neuromodulation of the autonomic fibers (parasympathetic and sympathetic) may play a key role in the management of headaches, stroke, or cerebral vasospasm. Another important structure within the PPF is the maxillary nerve (V2), which passes through the roof of the fossa. Here the trigeminal system is accessible for a reliable neuromodulation by targeting its second branch -the maxillary nerve- and this could be utilized in various painful conditions of the head and face.

Spinal cord stimulation in cluster headache.

Neurostimulation techniques for the treatment of primary headache syndromes, particularly for chronic cluster headache (CCH), have received much interest in the recent years. Occipital nerve stimulation (ONS) has yielded favourable clinical results, and is becoming a routine treatment for refractory chronic cluster headache in specialized centres. Meanwhile, other promising techniques, such as spinal cord stimulation (SCS) or sphenopalatine ganglion stimulation, are emerging. This article reviews the current state of clinical research for neurostimulation techniques for chronic cluster headache, and particularly the pros and cons of SCS and ONS.

Stimulation of the intrinsic cardiac autonomic nervous system results in a gradient of fibrillatory cycle length shortening across the atria during atrial fibrillation in humans.

INTRODUCTION: The intrinsic cardiac autonomic nervous system (ANS) is implicated in atrial fibrillation (AF) but little is known about its role in maintenance of the electrophysiological substrate during AF in humans. We hypothesized that ANS activation by high-frequency stimulation (HFS) of ganglionated plexi (GP) increases dispersion of atrial AF cycle lengths (AFCLs) via a parasympathetic effect. METHODS AND RESULTS: During AF in 25 patients, HFS was delivered to presumed GP sites to provoke a bradycardic vagal response and AFCL was continuously monitored from catheters placed in the pulmonary vein (PV), coronary sinus (CS), and high right atrium (HRA). A total of 163 vagal responses were identified from 271 HFS episodes. With a vagal response, the greatest reduction in AFCL was seen in the PV adjacent to the site of HFS (16% reduction, 166 ± 28 to 139 ± 26 ms, P < 0.0001) followed by the PV-atrial junction (9% reduction, 173 ± 21 to 158 ± 20 ms, P < 0.0001), followed by the rest of the atrium (3-7% reduction recorded in HRA and CS). Without a vagal response, AFCL changes were not observed. In 10 patients, atropine was administered in between HFS episodes. Before atropine administration, HFS led to a vagal response and a reduction in PV AFCL (164 ± 28 to 147 ± 26 ms, P < 0.0001). Following atropine, HFS at the same GP sites no longer provoked a vagal response, and the PV AFCL remained unchanged (164 ± 30 to 166 ± 33 ms, P = 0.34). CONCLUSIONS: Activation of the parasympathetic component of the cardiac ANS may cause heterogenous changes in atrial AFCL that might promote PV drivers.

Chronic augmentation of the parasympathetic tone to the atrioventricular node: a nonthoracotomy neurostimulation technique for ventricular rate control during atrial fibrillation.

INTRODUCTION: The right inferior ganglionated plexus (RIGP) selectively innervates the atrioventricular node. Temporary electrical stimulation of this plexus reduces the ventricular rate during atrial fibrillation (AF). We sought to assess the feasibility of chronic parasympathetic stimulation for ventricular rate control during AF with a nonthoracotomy intracardiac neurostimulation approach. METHODS AND RESULTS: In 9 mongrel dogs, the small endocardial area inside the right atrium, which overlies the RIGP, was identified by 20 Hz stimulation over a guiding catheter with integrated electrodes. Once identified, an active-fixation lead was implanted. The lead was connected to a subcutaneous neurostimulator. An additional dual-chamber pacemaker was implanted for AF induction by rapid atrial pacing and ventricular rate monitoring. Continuous neurostimulation was delivered for 1-2 years to decrease the ventricular rate during AF to a range of 100-140 bpm. Implantation of a neurostimulation lead was achieved within 37 +/- 12 min. The latency of the negative dromotropic response after on/offset or modulation of neurostimulation was <1 s. Continuous neurostimulation was effective and well tolerated during a 1-2 year follow-up with a stimulation voltage <5 V. The neurostimulation effect displayed a chronaxie-rheobase behavior (chronaxie time of 0.07 +/- 0.02 ms for a 50% decrease of the ventricular rate during AF). CONCLUSION: Chronic parasympathetic stimulation can be achieved via a cardiac neurostimulator. The approach is safe, effective, and well tolerated in the long term. The atrioventricular nodal selectivity and the opportunity to adjust the negative dromotropic effect within seconds may represent an advantage over pharmacological rate control.

An integrity test battery for the Nucleus Mini 22 Cochlear Implant System.

The probability of system failures increases as the number of cochlear implants increases throughout the world. Whether a malfunction is a technical or physiological problem remains to be defined, particularly in very young children, while a psychogenic hearing disorder after implantation must not be excluded in adults. The battery of objective measurements used clinically at the Medizinische Hochschule, Hannover has provided useful diagnostic information for distinguishing possible causes of failure. In a normally functioning device, an electrical signal equivalent to the biphasic rectangular stimulation pulse can be recorded by measuring skin potentials from surface electrodes placed on the mastoid of the implant side and the forehead. The signal from the stimulated implanted electrodes is derived by applying a constant pulse rate. Signal averaging is not necessary. If no signals are observed, a non-functioning device should be suspected. If the device works normally, function of the auditory pathways can be examined by recording the electrically elicited stapedius reflex or electrically evoked brain-stem responses. In our experience with more than 450 cochlear implant patients, eight internal device failures occurred, while an additional three patients had either reduced or no hearing sensations due to a disorder of the auditory pathways.