Mastication after craniotomy: pilot assessment of postoperative oral health-related quality of life.

BACKGROUND: Neurosurgical approaches to the brain often require the mobilization of the temporal muscle. Many patients complain of postoperative pain, atrophy, reduced mouth opening, and masticatory problems. Although the pterional, frontolateral-extended-pterional, and temporal craniotomies are the most frequently used approaches in neurosurgery, a systematic assessment of the postoperative oral health-related quality of life has never been performed so far. This study evaluates the oral health-related quality of life of patients after pterional, frontolateral-extended-pterional, or temporal craniotomy using a validated and standardized dental questionnaire, compares the results with the normal values of the general population, and investigates whether this questionnaire is sensitive to changes caused by surgical manipulation of the temporal muscle. METHODS: The "Oral Health Impact Profile" (OHIP14) is a validated questionnaire to assess the oral health-related quality of life. It asks the patients to assess their oral health situation within the past 7 days in 14 questions. Possible answers range from 0 (never) to 4 (very often). Sixty patients with benign intracranial processes operated through a lateral cranial approach were included. The questionnaire was answered before surgery (baseline) and 3 months and 15 months after surgery. RESULTS: Overall, postoperative OHIP scores increase significantly after 3 months and decrease after 15 months, but not to preoperative values. No factors can be identified which show a considerable relationship with the postoperative OHIP score. CONCLUSIONS: Postoperative impairment of mouth opening and pain during mastication can be observed 3 to 15 months after surgery and sometimes cause feedback from patients and their dentists. However, in line with existing literature, these complaints decrease with time. The study shows that the OHIP questionnaire is sensitive to changes caused by surgical manipulation of the temporal muscle and can therefore be used to investigate the influence of surgical techniques on postoperative complaints. Postoperatively, patients show worse OHIP scores than the general population, demonstrating that neurosurgical cranial approaches negatively influence the patient's oral health-related wellbeing. Larger studies using the OHIP questionnaire should evaluate if postoperative physical therapy, speech therapy, or specialized rehabilitation devices can improve the masticatory impairment after craniotomy. TRIAL REGISTRATION: Clinical trial register: DRKS00011096.

Implant-Mediated Therapy of Arterial Hypertension.

PURPOSE OF REVIEW: To give an overview on recent developments in permanent implant-based therapy of resistant hypertension. RECENT FINDINGS: The American Heart Association (AHA) recently updated their guidelines to treat high blood pressure (BP). As elevated BP now is defined as a systolic BP above 120 mmHg, the prevalence of hypertension in the USA has increased from 32% (old definition of hypertension) to 46%. In the past years, device- and implant-mediated therapies have evolved and extensively studied in various patient populations. Despite an initial drawback in a randomized controlled trial (RCT) of bilateral carotid sinus stimulation (CSS), new and less invasive and unilateral systems for baroreflex activation therapy (BAT) with the BAROSTIM NEO® have been developed which show promising results in small non-randomized controlled (RCT) studies. Selective vagal nerve stimulation (VNS) has been successfully evaluated in rodents, but has not yet been tested in humans. A new endovascular approach to reshape the carotid sinus to lower BP (MobiusHD™) has been introduced (baroreflex amplification therapy) with favorable results in non-RCT trials. However, long-term results are not yet available for this treatment option. A specific subgroup of patients, those with indication for a 2-chamber cardiac pacemaker, may benefit from a new stimulation paradigm which reduces the AV latency and therefore limits the filling time of the left ventricle. The most invasive approach for resistant hypertension still is the neuromodulation by deep brain stimulation (DBS), which has been shown to significantly lower BP in single cases. Implant-mediated therapy remains a promising approach for the treatment of resistant hypertension. Due to their invasiveness, such treatment options must prove superiority over conventional therapies with regard to safety and efficacy before they can be generally offered to a wider patient population. Overall, BAROSTIM NEO® and MobiusHD™, for which large RCTs will soon be available, are likely to meet those criteria and may represent the first implant-mediated therapeutical options for hypertension, while the use of DBS probably will be reserved for individual cases. The utility of VNS awaits appropriate assessment.

Intracortical polyimide electrodes with a bioresorbable coating.

Polyimide based shaft electrodes were coated with a bioresorbable layer to stiffen them for intracortical insertion and to reduce the mechanical mismatch between the target tissue and the implanted device after degradation of the coating. Molten saccharose was used as coating material. In a proof-of-concept study, the electrodes were implanted into the cortex of Wistar rats and the insertion forces during implantation were recorded. Electrochemical impedance spectroscopy was performed immediately after implantation and up to 13 weeks after implantation to monitor the tissue response to the implanted electrodes. The recorded spectra were modeled with an equivalent circuit to differentiate the influence of the single components. In one rat, a peak in the encapsulation resistance was observable after two weeks of implantation, indicating the peak of the acute inflammatory response. In another rat, the lowest resistances were observed after four weeks, indicating the termination of the acute inflammatory response. Multiunit activity was recorded with an adequate signal to noise ratio to allow spike sorting. Histology was performed after 7, 45 and 201 days of implantation. The results showed the highest tissue reaction after 45 days and confirmed impedance data that acute inflammatory reactions terminate over time.

Influence of Clonidine on Antihypertensive Selective Afferent Vagal Nerve Stimulation in Rats.

OBJECTIVE: Selective-afferent vagal nerve stimulation (sVNS) may be a treatment option for therapy-resistant hypertension, as it lowers blood pressure (BP) in rats without causing significant side effects. Alpha-2-agonists are widely used for the treatment of withdrawal, chronic pain and other disorders, and even if sVNS becomes a treatment option for therapy resistant hypertension, in some patients it might be necessary to combine sVNS with an alpha-2-agonist like clonidine. Alpha-2-agonists exhibit a central and peripheral mechanism of action. This study investigated the influence of the commonly used alpha-2-agonist clonidine on sVNS. MATERIALS AND METHODS: A polyimide multichannel-cuff-electrode was placed around the left vagal nerve bundle including the aortic depressor nerve (ADN) in eight male Wistar rats for the focused stimulation of baroreceptive fibers of the ADN. Stimulation parameters were adapted to the thresholds of the individual animals and ranged from frequencies between 30 and 50 Hz, amplitudes of 0.5-0.9 mA and pulse widths between 0.4 and 0.8 ms. BP was recorded using a microtip transducer in the left carotid artery, and electrocardiography was registered using subcutaneous needle electrodes. RESULTS: Before clonidine, we found a frequency-dependent drop of BP with maximum at 40 Hz. The animals' mean arterial blood pressures and respiration rate dropped after intravenous clonidine administration (10 µg/kg bodyweight), and sVNS still decreased in BP, but they did so to a lesser extent. Unwanted bradycardia, which was expected by the superimposition of sVNS and clonidine, did not occur. Left-sided vagotomy abolished the respiratory depressant effect of clonidine and blunted the BP reducing effect of sVNS while sVNS hardly affected heart rate anymore. CONCLUSIONS: The effect of sVNS on BP is dampened by clonidine, but sVNS can still lower the BP in clonidine treated rats without causing significant bradycardia.

Assessment of postoperative pain, dysesthesia, and weather sensitivity after pterional and temporal neurosurgical approaches.

OBJECTIVE: Many neurosurgical approaches require incision of the temporal muscle (TM). Consequently, patients often report reduced opening of the mouth, facial asymmetry, numbness, and pain after lateral craniotomies. A systematic assessment of these postoperative subjective complaints is lacking in the literature. Therefore, in this study, the authors evaluate subjective complaints after pterional, frontolateral-extended pterional, or temporal craniotomy using a 6-item questionnaire. They examine the association of these subjective complaints with the extent of the mobilization of the TM. METHODS: The questionnaire assessed complaints about limited opening of the mouth, pain in the mastication muscles, facial asymmetry, sensory deficits in the temporal region, weather sensitivity, and headache. Eligible patients with benign intracranial processes operated on using lateral cranial approaches between 2016 and 2019 were included. The questionnaire was answered before surgery (baseline) and 3 and 15 months after surgery. Surgeons documented the extent of TM incision. RESULTS: Among the 55 patients in this study, all complaints apart from headache showed an increase at a statistically significant rate at 3 months postoperatively, that is, limited mouth opening (p < 0.0001), pain in the mastication muscles (p < 0.0001), an impression of asymmetry in the mastication muscles (p = 0.0002), sensory disturbances in the temporal region (p < 0.0001), and weather sensitivity (p < 0.001). Only pain in the mastication muscles showed a relevant decrease at 15 months postsurgery (p = 0.058). The extent of the mobilized TM was associated with pain in the mastication muscles at 3 months (p = 0.0193). CONCLUSIONS: Subjective complaints in patients following lateral craniotomy can be detected. As the extent of the mobilized TM relevantly influenced pain in the mastication muscles, the authors conclude that one should sparsely mobilize the TM. Furthermore, a neurosurgeon should be aware and warn the patient of subjective postoperative complaints and inform the patient about their natural course.

Target-approaching behavior of barn owls (Tyto alba): influence of sound frequency.

We studied the influence of frequency on sound localization in free-flying barn owls by quantifying aspects of their target-approaching behavior to a distant sound source during ongoing auditory stimulation. In the baseline condition with a stimulus covering most of the owls hearing range (1-10 kHz), all owls landed within a radius of 20 cm from the loudspeaker in more than 80% of the cases and localization along the azimuth was more accurate than localization in elevation. When the stimulus contained only high frequencies (>5 kHz) no changes in striking behavior were observed. But when only frequencies from 1 to 5 kHz were presented, localization accuracy and precision decreased. In a second step we tested whether a further border exists at 2.5 kHz as suggested by optimality models. When we compared striking behavior for a stimulus having energy from 2.5 to 5 kHz with a stimulus having energy between 1 and 2.5 kHz, no consistent differences in striking behavior were observed. It was further found that pre-takeoff latency was longer for the latter stimulus than for baseline and that center frequency was a better predictor for landing precision than stimulus bandwidth. These data fit well with what is known from head-turning studies and from neurophysiology.

Effect of selective vagal nerve stimulation on blood pressure, heart rate and respiratory rate in rats under metoprolol medication.

Selective vagal nerve stimulation (sVNS) has been shown to reduce blood pressure without major side effects in rats. This technology might be the key to non-medical antihypertensive treatment in patients with therapy-resistant hypertension. ß-blockers are the first-line therapy of hypertension and have in general a bradycardic effect. As VNS itself can also promote bradycardia, it was the aim of this study to investigate the influence of the ß1-selective blocker Metoprolol on the effect of sVNS especially with respect to the heart rate. In 10 male Wistar rats, a polyimide multichannel-cuff electrode was placed around the vagal nerve bundle to selectively stimulate the aortic depressor nerve fibers. The stimulation parameters were adapted to the thresholds of individual animals and were in the following ranges: frequency 30-50 Hz, amplitude 0.3-1.8 mA and pulse width 0.3-1.3 ms. Blood pressure responses were detected with a microtip transducer in the carotid artery, and electrocardiography was recorded with s.c. chest electrodes. After IV administration of Metoprolol (2 mg kg(-1) body weight), the animals' mean arterial blood pressure (MAP) and heart rate (HR) decreased significantly. Although the selective electrical stimulation of the baroreceptive fibers reduced MAP and HR, both effects were significantly alleviated by Metoprolol. As a side effect, the rate of stimulation-induced apnea significantly increased after Metoprolol administration. sVNS can lower the MAP under Metoprolol without causing severe bradycardia.

Haemodynamic Responses to Selective Vagal Nerve Stimulation under Enalapril Medication in Rats.

Selective vagal nerve stimulation (sVNS) has been demonstrated to lower blood pressure (BP) in rats without causing major side effects. This method might be adapted for the treatment of therapy-resistant hypertension in patients. Converting enzyme inhibitors (CEIs) are among the first drugs that are administered for arterial hypertension and prominently reduce BP primarily by interacting with the renin-angiotensin system of the kidneys. Beyond the reduction of BP, CEI have a positive effect on the survival rate after myocardial infarction; they reduce the rates of stroke and improve the neurohormonal status in heart-failure patients. If sVNS might be introduced as a therapy against resistant hypertension, patients will at least partially stay on their CEI medication. It is therefore the aim of this study to investigate the influence of the CEI enalapril on the haemodynamic and respiratory effects of sVNS. In 10 male Wistar rats, a polyimide-based multichannel-cuff-electrode was placed around the vagal nerve bundle to selectively stimulate the aortic depressor nerve fibres. Stimulation parameters were adapted to the thresholds of the individual animals and included repetition frequencies between 30 and 50 Hz, amplitudes of 0.5 to 1.5 mA and pulse widths between 0.4 ms and 1.0 ms. BP responses were detected with a microtip transducer in the left carotid artery, and electrocardiography was recorded with subcutaneous electrodes. After intravenous administration of enalapril (2 mg/kg bodyweight), the animals' mean arterial blood pressures (MAPs) decreased significantly, while the heart rates (HRs) were not significantly influenced. The effects of sVNS on BP and HR were attenuated by enalapril but were still present. We conclude that sVNS can lower the MAP during enalapril treatment without relevant side effects.

Epoxy casting used as nonhermetic encapsulation technique for implantable electronic devices.

Implantable medical applications experienced a rapid growth since starting in the late 1950s with the first pacemakers. However, there are only two main packaging strategies available to protect the implanted electronics from the body environment. While hermetic packaging oftentimes seems to be more feasible, nonhermetic encapsulation can be an alternative under certain conditions. Previous studies using commercially available USB flash drives (UFD) pointed out the feasibility of using epoxy resins as encapsulant material. Based on this study, the water uptake was measured according to ISO 294-3 to determine the water diffusion rate of three EPO-TEK (ET) epoxies. The average water uptake Me for ET 301 was 3.18 %mass, for ET 301-2 it was 1.81 %mass and for ET 302-3M it was 2.34 %mass. The calculated diffusion constant D for ET 301 was 3.61E-13 m2/s, for ET 301-2 it was 3.63E-13 m2/s and for ET 302-3M it was found at 1.98E-13 m2/s. Next, we developed a setup in which eight microcontrollers were fully casted into two selected types of epoxies, four respectively. The casted microcontrollers where immersed in phosphate buffered saline (PBS, pH=7.4) and incubated at a temperature of 37 °C corresponding to the human body core temperature. The electronics were tested for 78 days without malfunctioning.

Effect of Cardiac-Cycle-Synchronized Selective Vagal Stimulation on Heart Rate and Blood Pressure in Rats.

INTRODUCTION: Activation of the baroreflex system through the selective vagal nerve stimulation (sVNS) may become a treatment option for therapy-resistant hypertension, which is a frequently observed problem in the antihypertensive therapy. In previous studies, we used continuous sVNS to lower blood pressure (BP) without major side effects in a rat model. As continuous stimulation is energy consuming and sVNS could be implemented in an antihypertensive stimulator, it was the aim of this study to investigate the efficacy of pulsatile, cardiac-cycle-synchronized sVNS (cssVNS) on the reduction of BP. METHODS: A multichannel cuff electrode was wrapped around the left vagal nerve in six male Wistar rats under Isoflurane anesthesia. BP was recorded in the left carotid artery. An electrocardiogram (ECG) was obtained via subcutaneous needle electrodes. The aortic depressor nerve fibers in the vagal nerve bundle were selectively stimulated with 18 parameter settings within a window of 15-30 ms after the R-peak in the ECG. The stimulation paradigm included every heartbeat, every second heart beat, and every third heart beat. BP and heart rate were initially recorded over 10 min. RESULTS: Using cssVNS, BP could be significantly reduced over 30 min and maintained at this level. While the highest BP reduction was seen during cssVNS at every heartbeat with minimal bradycardia, less-yet significant-BP reduction was seen during cssVNS at every second or third heartbeat without causing detectable bradycardia. CONCLUSION: cssVNS can chronically reduce BP in rats avoiding measurable bradycardic side effects. This energy-efficient technique might allow the implementation of sVNS using an implantable device to permanently lower BP in patients. FUNDING: The study was funded by Bundesministerium fur Bildung und Forschung/German Federal Ministry of Education and Research among the call "Individualisierte Medizintechnik" under the grant number FKZ 13GW0120B.

Non-hermetic encapsulation for implantable electronic devices based on epoxy.

Hermetic and non-hermetic implant packaging are the two strategies to protect electronic systems from the humid conditions inside the human body. Within the scope of this work twelve different material combinations for a non-hermetic, high-reliable epoxy based encapsulation technique were characterized. Three EPO-TEK (ET) epoxies and one low budget epoxy were chosen for studies with respect to their processability, water vapor transmission rate (WVTR) and adhesion to two different ceramic-based substrates as well as to one standard FR4-substrate. Setups were built to analyze the mentioned properties for at least 30 days using an aging test in a moist environment. As secondary test subjects, commercially available USB flash drives (UFD) were successfully encapsulated inside the epoxies, soaked in phosphate buffered saline (PBS, pH=7.4), stored in an incubator (37°C) and tested for 256 days without failure. By means of epoxy WVTR (0.0278 g/day/m(2)) and degrease of adhesion (24.59 %) during 30 days in PBS, the combination of the standard FR4-substrate and the epoxy ET 301-2 was found to feature the best encapsulation properties. If a ceramic-based electronic system has to be used, the most promising combination consists of the alumina substrate and the epoxy ET 302-3M (WVTR: 0.0588 g/day/m(2); adhesion drop: 49.58 %).

Blood pressure control with selective vagal nerve stimulation and minimal side effects.

OBJECTIVE: Hypertension is the largest threat to patient health and a burden to health care systems. Despite various options, 30% of patients do not respond sufficiently to medical treatment. Mechanoreceptors in the aortic arch relay blood pressure (BP) levels through vagal nerve (VN) fibers to the brainstem and trigger the baroreflex, lowering the BP. Selective electrical stimulation of these nerve fibers reduced BP in rats. However, there is no technique described to localize and stimulate these fibers inside the VN without inadvertent stimulation of non-baroreceptive fibers causing side effects like bradycardia and bradypnea. APPROACH: We present a novel method for selective VN stimulation to reduce BP without the aforementioned side effects. Baroreceptor compound activity of rat VN (n = 5) was localized using a multichannel cuff electrode, true tripolar recording and a coherent averaging algorithm triggered by BP or electrocardiogram. MAIN RESULTS: Tripolar stimulation over electrodes near the barofibers reduced the BP without triggering significant bradycardia and bradypnea. The BP drop was adjusted to 60% of the initial value by varying the stimulation pulse width and duration, and lasted up to five times longer than the stimulation. SIGNIFICANCE: The presented method is robust to impedance changes, independent of the electrode's relative position, does not compromise the nerve and can run on implantable, ultra-low power signal processors.

BaroLoop: using a multichannel cuff electrode and selective stimulation to reduce blood pressure.

The therapy of refractory hypertension is an increasing problem for health care systems and a frontend in research in both pharmacology and neuroelectronic engineering. Overriding the baroreceptive information of afferent nerve fibers, originating from pressure sensors in the aortic arch, can trigger the baroreflex, a systemic control system that lowers the blood pressure (BP) almost instantaneously. Using a multichannel cuff electrode, wrapped around a rat vagal nerve, we were able to regulate the BP using selective, tripolar stimulation. The tripolar stimulation was sufficiently selective to not trigger any unwanted side effects like bradycardia or bradypnea. The BP was reduced best with charge balanced stimulation amplitudes of 1 mA and pulse duration of 0.3 ms. The stimulation frequency had only a mild influence on the effectiveness of the stimulation and did work best at 40 Hz. We found that the BP took up to five times the stimulation period to recover to the value prior to stimulation.

Computational tissue volume reconstruction of a peripheral nerve using high-resolution light-microscopy and reconstruct.

The development of neural cuff-electrodes requires several in vivo studies and revisions of the electrode design before the electrode is completely adapted to its target nerve. It is therefore favorable to simulate many of the steps involved in this process to reduce costs and animal testing. As the restoration of motor function is one of the most interesting applications of cuff-electrodes, the position and trajectories of myelinated fibers in the simulated nerve are important. In this paper, we investigate a method for building a precise neuroanatomical model of myelinated fibers in a peripheral nerve based on images obtained using high-resolution light microscopy. This anatomical model describes the first aim of our "Virtual workbench" project to establish a method for creating realistic neural simulation models based on image datasets. The imaging, processing, segmentation and technical limitations are described, and the steps involved in the transition into a simulation model are presented. The results showed that the position and trajectories of the myelinated axons were traced and virtualized using our technique, and small nerves could be reliably modeled based on of light microscopy images using low-cost OpenSource software and standard hardware. The anatomical model will be released to the scientific community.

Detection of baroreceptor activity in rat vagal nerve recording using a multi-channel cuff-electrode and real-time coherent averaging.

Electrical stimulation of afferent nerve fibers originating from pressure sensors can trigger the baroreflex to reduce blood pressure and might be an alternative to treat patients with hypertension. In this study, baroreceptor compound activity was detected using multi-channel cuff-electrode recordings on rat vagal nerve. In order to isolate the vagal nerve signals from external potentials (such as ECG- and EMG-coupling), a tripolar measuring technique was applied. To eliminate noise and neural signals corresponding to other organs, coherent averaging was used. The baroreceptor-correlated signals appear predominantly in one of the electrode channels, presumably close to the corresponding neural substrate. This localization was done in real-time.

In-flight corrections in free-flying barn owls (Tyto alba) during sound localization tasks.

Barn owls localize a stationary auditory target with high accuracy. They might also be able to hit a target that is intermittently moving while the owl is approaching. If so, there should be a critical delay before strike initiation, up to which the owl can adapt its flight path to a new stimulus position. In this study, this critical stimulus delay was determined in a three-dimensional free-flight paradigm. Barn owls localized a pulsed broadband noise while sitting on a perch in total darkness. This initial signal stopped with the owl's take-off and an in-flight stimulus (target sound), lasting 200 ms, was introduced at variable time delays (300-1200 ms) during the approximate flight time of 1300 ms. The owls responded to the in-flight signal with a corrective head and body turn. The percentage of trials in which correction turns occurred (40-80%) depended upon the individual bird, but was independent of the stimulus delay within a range of 800 ms after take-off. Correction turns strongly decreased at delays >or=800 ms. The landing precision of the owls, defined as their distance to the in-flight speaker, did not decrease with increasing stimulus delay, but decreased if the owl failed to perform a correction turn towards that speaker. Landing precision was higher for a short (50 cm) than for a large (100 cm) distance between the initial and the new target. Thus, the ability of barn owls to adapt their flight path to a new sound target depends on the in-flight stimulus delay, as well as on the distance between initial and novel targets.

A hydrodynamic topographic map in the midbrain of goldfish Carassius auratus.

Sensory systems often consist of several parallel pathways. Within each pathway, sensory information may be processed in topographically arranged maps or in maps derived by neuronal computation. Parallel pathways have so far not been described in the central lateral line system of teleost fish at levels higher than the medulla, and evidence for midbrain lateral line maps in fish is still weak. We found two classes of units with different response patterns in the central lateral line nucleus in the torus semicircularis of the goldfish Carassius auratus. Units of one class responded to a passing sphere and to the wake caused by that sphere with excitation. Units of the second class also responded to the moving sphere. However, these units did not respond to the wake behind the sphere. Hydrodynamic information received by class two units was topographically organized in the torus semicircularis of goldfish in that anterior body areas projected to rostral midbrain and posterior body areas to caudal midbrain. Units that responded only to the passing sphere were on average located more ventrally in the lateral TS than the units that responded exclusively to a vibrating sphere.

Neuronal encoding of ultrasonic sound by a fish.

Many species of odontocete cetaceans (toothed whales) use high-frequency clicks (60-170 kHz) to identify objects in their environment, including potential prey. Behavioral studies have shown that American shad, Alosa sapidissima, can detect ultrasonic signals similar to those of odontocetes that are potentially their predators. American shad also show strong escape behavior in response to ultrasonic pulses between 70 and 110 kHz and can determine the location of the sound source at least in the horizontal plane. The present study examines physiological aspects of ultrasound detection by American shad and provides the first insights into the neural encoding of ultrasound signals in any nonmammalian vertebrate. The recordings were obtained by penetration through the cerebellar surface. All but two units responded exclusively to ultrasound. Ultrasound-sensitive units did not phase-couple to any stimulus frequency. Some units resembled the response of constant latency neurons found in the ventral nucleus of the lateral lemniscus of bats. We suggest that ultrasonic and sonic signals are processed along different pathways in Alosa. The ultrasonic pathway in Alosa appears to be a feature detector that is likely to be adapted (e.g., frequency, intensity) to odontocete echolocation signals.