Amelioration of Anxiety Associated with Opioid Withdrawal by Activation of Spinal Mechanoreceptors Via Novel Heterodyned Whole Body Vibration.

Objectives: Opioid use disorder (OUD)-associated overdose deaths have reached epidemic proportions worldwide. An important driving force for relapse is anxiety associated with opioid withdrawal. We hypothesized that our new technology, termed heterodyned whole-body vibration (HWBV) would ameliorate anxiety associated with OUD. Methods: Using a randomized, placebo (sham)-controlled, double-blind study design in an NIH-sponsored Phase 1 trial, we evaluated 60 male and 26 female participants diagnosed with OUD and undergoing treatment at pain and rehabilitation clinics. We utilized the Hamilton Anxiety Scale (HAM-A) and a daily visual analog scale anxiety rating (1-10) to evaluate anxiety. Subjects were treated for 10 min 5X/week for 4 weeks with either sham vibration (no interferential beat or harmonics) or HWBV (beats and harmonics). The participants also completed a neuropsychological test battery at intake and discharge. Results: In OUD subjects with moderate anxiety, there was a significant improvement in daily anxiety scores in the HWBV group compared to the sham treatment group (p=3.41 × 10-7). HAM-A scores in OUD participants at intake showed moderate levels of anxiety in OUD participants (HWBV group: 15.9 ± 1.6; Sham group: 17.8 ± 1.6) and progressively improved in both groups at discharge, but improvement was greater in the HWBV group (p=1.37 × 10-3). Furthermore, three indices of neuropsychological testing (mental rotations, spatial planning, and response inhibition) were significantly improved by HWBV treatment. Conclusions: These findings support HWBV as a novel, non-invasive, non-pharmacological treatment for anxiety associated with OUD.

Noninvasive detection of elevated ICP using spontaneous tympanic membrane pulsation.

Neurological conditions such as traumatic brain injury (TBI) and hydrocephalus may lead to intracranial pressure (ICP) elevation. Current diagnosis methods rely on direct pressure measurement, while CT, MRI and other expensive imaging may be used. However, these invasive or expensive testing methods are often delayed because symptoms of elevated ICP are non-specific. Invasive methods, such as intraventricular catheter, subdural screw, epidural sensor, lumbar puncture, are associated with an increased risk of infection and hemorrhage. On the other hand, noninvasive, low-cost, accurate methods of ICP monitoring can help avoid risks and reduce costs while expediting diagnosis and treatment. The current study proposes and evaluates a novel method for noninvasive ICP monitoring using tympanic membrane pulsation (TMp). These signals are believed to be transmitted from ICP to the auditory system through the cochlear aqueduct. Fifteen healthy subjects were recruited and TMp signals were acquired noninvasively while the subjects performed maneuvers that are known to change ICP. A custom made system utilizing a stethoscope headset and a pressure transducer was used to perform these measurements. Maneuvers included head-up-tilt, head-down-tilt and hyperventilation. When elevated ICP was induced, significant TMp waveform morphological changes were observed in each subject (p < 0.01). These changes include certain waveform slopes and high frequency wave features. The observed changes were reversed by the maneuvers that decreased ICP (p < .01). The study results suggest that TMp waveform measurement and analysis may offer an inexpensive, noninvasive, accurate tool for detection and monitoring of ICP elevations. Further studies are warranted to validate this technique in patients with pathologically elevated ICP.

The Effect of Beat Frequency Vibration on Sleep Latency and Neural Complexity: A Pilot Study.

Insomnia affects millions of people worldwide, and non-pharmacological treatment options are limited. A bed excited with multiple vibration sources was used to explore beat frequency vibration (BFV) as a non-pharmacological treatment for insomnia. A repeated measures design pilot study of 14 participants with mild-moderate insomnia symptom severity (self-reported on the Insomnia Severity Index) was conducted to determine the effects of BFV, and traditional standing wave vibration (SWV) on sleep latency and sleep electrocortical activity. Participants were monitored using high-density electroencephalography (HD-EEG). Sleep latency was compared between treatment conditions. A trend of decreasing sleep latency due to BFV was found for unequivocal sleep latency (p ≤ 0.068). Neural complexity during wake, N1, and N2 stages were compared using Multi-Scale Sample Entropy (MSE), which demonstrated significantly lower MSE between wake and N2 stages (p ≤ 0.002). During N2 sleep, BFV showed lower MSE than the control session in the left frontoparietal region. As a measure of information integration, reduced entropy may indicate that BFV decreases conscious awareness during deeper stages of sleep. SWV caused reduced alpha activity and increased delta activity during wake. BFV caused increased delta activity during N2 sleep. These preliminary results suggest that BFV may help decrease sleep latency, reduce conscious awareness, and increase sleep drive expression during deeper stages of sleep. SWV may be beneficial for decreasing expression of arousal and increasing expression of sleep drive during wake, implying that beat frequency vibration may be beneficial to sleep.

The "Brain Stethoscope": A Non-Invasive Method for Detecting Elevated Intracranial Pressure.

Introduction Minimally invasive intracranial pressure (ICP) screening has long been desired by neurosurgeons. A novel approach deriving ICP from tympanic membrane (TM) pulsation may offer the solution. The ICP waveform appears to be transmitted to the TM by the cochlear aqueduct. The resulting TM infrasonic pulsations can be measured by certain sensors. Elevated ICP alters brain compliance, which appears to yield slower rise times of the TM pulsation waveform. Measurement of this change may be useful in screening for elevated ICP. This paper investigates one such technique. Methods A stethoscope was modified for airtight external ear canal fit; the dome was exchanged for a magnetic reluctance pressure sensor, allowing measurement of TM pulsations. Analog TM pulsations were analyzed by measuring the pulsation's slope ratio between the waveform's downslope and upslope. Seventeen normal subjects (ages 18-32 years) underwent hyperventilation and tilt table testing to induce ICP changes. An algorithm processed this data and predicted the subject's ICP status. Results The slope ratio method showed consistent and stable changes with the expected alterations in ICP from the tilt test and hyperventilation maneuvers. The classification algorithm correctly identified subjects with elevated ICP in 60 of 60 independent recordings on 17 subjects. Conclusion This paper has four conclusions. First, the "brain stethoscope" can detect increased ICP from the TM pulsation waveform in healthy subjects. Second, analysis of the TM waveform using slope ratio calculations is capable of distinguishing normal versus elevated ICP. Third, the tilt and hyperventilation maneuvers showed the expected physiologic trends. Last, further studies are needed on patients with pathological ICP before the brain stethoscope can be implemented into clinical practice.

Isolated Fourth Ventricle: To Shunt or Stent.

BACKGROUND: Of the various management options for isolated fourth ventricle (IFV), fourth ventriculoperitoneal shunts (FVPS) and aqueductal stents (AST) have been the most favored. Though effective, FVPS are often difficult to place and have higher complication rates than conventional ventricular shunts. OBJECTIVE: To assess the efficacy of AST in IFV and compare the outcome with FVPS. METHODS: Twenty-five patients surgically treated for IFV were analyzed. In all, a preoperative magnetic resonance imaging assessed the extent of aqueductal obstruction. Patients with an identified short-segment aqueductal stenosis were considered for AST placement; those with long-segment aqueductal obstruction underwent FVPS. RESULTS: Of the 25, 12 were symptomatic, while 13 were asymptomatic (progressive dilation of IFV in 9, persistent dilation with distortion of the brain stem in 4). In 3 with normal ventricles, the ventricles had to be dilated by externalizing the shunt before placing the stent. Nineteen underwent AST placement, whereas in 6 FVPS was performed. Sixteen patients underwent a simultaneous cerebrospinal fluid diversion procedure and fourth ventricular decompression. At follow-up (mean: 45 mo), stent migration was observed in 2 patients. In the FVPS group, 1 had 2 shunt revisions while another developed reversible cranial nerve paresis. Though a reduction of the IFV was observed with both procedures, the extent of reduction was more with FVPS. CONCLUSION: Both FVPS and AST are effective in managing IFV. The extent of aqueductal obstruction and degree of ventriculomegaly are often the deciding factors in choosing the management option.

Ferromagnetic Heating for Vessel Sealing and Division: Utility and Comparative Study to Ultrasonic and Bipolar Technologies.

INTRODUCTION: Vessel sealing technologies have improved surgical efficiency and outcomes. Ferromagnetic technology has potential utility in this area. The aim of this study was to evaluate ferromagnetic heating in sealing and dividing vessels. METHODS: A novel ferromagnetic (FM) sealer, FMsealer, was developed for sealing and dividing vessels. Using a swine in vivo model, the following endpoints were evaluated: (1) proof of concept, (2) 21-day survival surgery, and (3) comparison with ultrasonic (US) and/or bipolar (BP) devices for subjective outcomes. Seal burst strengths were measured in vitro. Mann-Whitney and Student's t test were used. RESULTS: After showing proof of concept, 5 swine underwent survival splenectomy, nephrectomy, hysterectomy, and mesenteric vessel division (arteries ranging from 1 to 7 mm in diameter) with necropsy after day 21 showing no evidence of surgical site bleeding. FM was equivalent to BP in tissue retention and superior to BP in spread/tissue desiccation, sticking, and charring (P ≤ .01). The FM was superior to US and BP in speed of 10 cm mesentery division (mean ± SD seconds): FM (12.9 ± 1.0 seconds), US (23.3 ± 4.4 seconds), BP (46.1 ± 5.2 seconds) (P ≤ .01 FM vs US or BP). Seal burst strength and success of sealing a 5-mm carotid artery were as follows (mean ± SD mmHg, % success burst strength >240 mm Hg): FM (710 ± 206 mm Hg, 94% success), US (848 ± 565 mm Hg, 79%), and BP (619 ± 373 mm Hg, 83%). CONCLUSION: Ferromagnetic heating is an effective and efficient technology for sealing and dividing of vessels. An initial prototype of the FMsealer compared favorably with commercially available products based on ultrasonic and bipolar technologies.

Intracranial electrical impedance tomography: a method of continuous monitoring in an animal model of head trauma.

BACKGROUND: Electrical impedance tomography (EIT) is a method that can render continuous graphical cross-sectional images of the brain's electrical properties. Because these properties can be altered by variations in water content, shifts in sodium concentration, bleeding, and mass deformation, EIT has promise as a sensitive instrument for head injury monitoring to improve early recognition of deterioration and to observe the benefits of therapeutic intervention. This study presents a swine model of head injury used to determine the detection capabilities of an inexpensive bedside EIT monitoring system with a novel intracranial pressure (ICP)/EIT electrode combination sensor on induced intraparenchymal mass effect, intraparenchymal hemorrhage, and cessation of brain blood flow. Conductivity difference images are shown in conjunction with ICP data, confirming the effects. METHODS: Eight domestic piglets (3-4 weeks of age, mean 10 kg), under general anesthesia, were subjected to 4 injuries: induced intraparenchymal mass effect using an inflated, and later, deflated 0.15-mL Fogarty catheter; hemorrhage by intraparenchymal injection of 1-mL arterial blood; and ischemia/infarction by euthanasia. EIT and ICP data were recorded 10 minutes before inducing the injury until 10 minutes after injury. Continuous EIT and ICP monitoring were facilitated by a ring of circumferentially disposed cranial Ag/AgCl electrodes and 1 intraparenchymal ICP/EIT sensor electrode combination. Data were recorded at 100 Hz. Two-dimensional tomographic conductivity difference (Δσ) images, rendered using data before and after an injury, were displayed in real time on an axial circular mesh. Regions of interest (ROI) within the images were automatically selected as the upper or lower 5% of conductivity data depending on the nature of the injury. Mean Δσ within the ROIs and background were statistically analyzed. ROI Δσ was compared with the background Δσ after an injury event using an unpaired, unequal variance t test. Conductivity change within an ROI after injury was likewise compared with the same ROI before the injury making use of unpaired t tests with unequal variance. RESULTS: Eight animal subjects were studied, each undergoing 4 injury events including euthanasia. Changes in conductivity due to injury showed expected pathophysiologic effects in an ROI identified within the middle of the left hemisphere; this localization is reasonable given the actual site of injury (left hemisphere) and spatial warping associated with estimating a 3-dimensional conductivity distribution in 2-dimensional space. Results are shown as mean ± 1 SD. When averaged across all 8 animals, balloon inflation caused the mean Δσ within the ROI to shift by -11.4 ± 10.9 mS/m; balloon deflation by +9.4 ± 8.8 mS/m; blood injection by +19.5 ± 11.5 mS/m; death by -12.6 ± 13.2 mS/m. All induced injuries were detectable to statistical significance (P < 0.0001). CONCLUSION: This study confirms that the bedside EIT system with ICP/EIT combination sensor can detect induced trauma. Such a technique may hold promise for further research in the monitoring and management of traumatically brain-injured individuals.

Pediatric cranial vault defects: early experience with beta-tricalcium phosphate bone graft substitute.

Pediatric calvarial defects may result from numerous causes. Availability of bone is often limited because of the child's age, and bone substitutes may be needed to reconstruct the defects. A bone substitute composed of ultraporous beta-tricalcium phosphate (Orthovita, Malvern, PA) is an osteoconductive product successfully used in orthopedic surgery. However, its application in cranial vault reconstruction is largely unstudied. The purpose of this investigation was to determine the healing rate of bone defects with the use of this product.A retrospective review was performed of patients in whom beta-tricalcium phosphate was used. Patient population consisted of 23 patients. Mean surgical age was 35 months. Reconstructions consisted of 20 craniosynostosis corrections and 3 posttraumatic repairs. The average defect size was 37 cm (range, 4.6-210 cm). Average follow-up was 12.7 months.At 2 months, 19 (79%) of 23 patients achieved healing of their defect, defined as the absence of persistent bone gaps. Persistent areas of bone weakness occurred in 3 patients at 4 months and 2 patients at 6 months. By 9 months, only 1 patient had not healed. This patient had the largest original defect of 210 cm. Defects taking longer than 2 months to heal measured 83 cm, whereas healed defects were 32 cm. No patients required treatment for graft-related problems such as infection or exposure.Early experience with beta-tricalcium phosphate bone substitute shows good healing of pediatric calvarial vault defects by 2 months, with no graft-associated complications. It seems most effective in the repair of smaller defects less than 40 cm.

A study of family head shape: environment alters cranial shape.

A change in the type of cranial deformities (plagiocephaly) presenting to certain clinics has occurred. The purpose of this study was to compare infant head shapes against head shapes of their biologic parents to explore the roles of heredity and environment on cranial shape. Standardized family photographs and anthropometric measurements demonstrated that 30% of the infants had cranial widths 2 standard deviations above norm, while 4.6% had widths exceeding 3 standard deviations. Despite a mean age of only 8 months, 11.6% had widths that were already greater than that of 1 parent. These results demonstrate that plagiocephaly has taken on a new configuration, presenting not only with asymmetry, but also with excessive cranial width.

Endoscopic aqueductoplasty and interventriculostomy for the treatment of isolated fourth ventricle in children.

OBJECTIVE: There are different approaches for the treatment of isolated fourth ventricle in children, including a suboccipital ventriculoperitoneal shunt, suboccipital craniotomy with microsurgical fenestration, and endoscopic fenestration. We discuss the indications, surgical methods, and outcome of 18 patients who underwent endoscopic treatment for isolated fourth ventricle. METHODS: We retrospectively reviewed the medical histories of 18 patients with an isolated fourth ventricle. Surgical procedures included endoscopic aqueductoplasty, endoscopic aqueductoplasty with a stent, endoscopic interventriculostomy (lateral ventricle or third ventricle to fourth ventricle), and endoscopic interventriculostomy with a stent. Operations were performed between July 1997 and June 2002. The mean age of the patients at the time of surgery was 3 years. The mean follow-up was 29 months. All patients had a supratentorial ventriculoperitoneal shunt. RESULTS: Clinical symptoms (impairment of consciousness, tetraparesis, and ataxia) improved in all patients. Reduction of the size of the fourth ventricle was observed in all patients. Seven patients required reoperation because of restenosis (39% revision rate). Restenosis occurred between 2 weeks and 7 months after surgery (average, 3 mo). Four patients underwent reoperation with stent placement, and three patients underwent reaqueductoplasty. We had the following complications: one infection, one asymptomatic subdural hygroma, one transient oculomotor paresis, and one permanent oculomotor paresis (4 [22%] of 18 patients). CONCLUSION: The significant failure rate of fourth ventricle shunts has led to the development of alternative treatment methods. Endoscopic aqueductoplasty or interventriculostomy presents an effective, minimally invasive, and safe procedure for the treatment of isolated fourth ventricle in pediatric patients. Compared with suboccipital craniotomy and microsurgical fenestration, endoscopic aqueductoplasty is less invasive, and compared with fourth ventricle shunts, it is more reliable and effective.

Endoscopically assisted retrieval of an intracranial air gun pellet.

Intracranial missile injuries often lodge in deep and inaccessible areas of the brain and are sometimes difficult to remove. Many such missiles are left behind for the fear of surgical morbidity. The authors report the successful removal of a deep-seated intracranial air gun pellet with the aid of an endoscope. A 4-year-old child was admitted after being injured by an air gun pellet in the left forehead. He had no neurological deficits. Cranial CT scan revealed evidence of a pellet lodged in the left frontal region with small bone fragments driven into the adjacent parenchyma. The patient underwent a left frontal craniotomy around the entry wound and debridement of the bone fragments. The track was explored carefully with the aid of a rigid fiberscope and the pellet was identified and removed easily. Postoperatively, the patient had an uneventful recovery. Endoscopic retrieval of the projectile by following the track may be considered a reasonable alternative in suitable cases. This might be useful in retrieving deep-seated missiles.

Implementation, calibration and accuracy testing of an image-enhanced endoscopy system.

This paper presents a new method for image-guided surgery called image-enhanced endoscopy. Registered real and virtual endoscopic images (perspective volume renderings generated from the same view as the endoscope camera using a preoperative image) are displayed simultaneously; when combined with the ability to vary tissue transparency in the virtual images, this provides surgeons with the ability to see beyond visible surfaces and, thus, provides additional exposure during surgery. A mount with four photoreflective spheres is rigidly attached to the endoscope and its position and orientation is tracked using an optical position sensor. Generation of virtual images that are accurately registered to the real endoscopic images requires calibration of the tracked endoscope. The calibration process determines intrinsic parameters (that represent the projection of three-dimensional points onto the two-dimensional endoscope camera imaging plane) and extrinsic parameters (that represent the transformation from the coordinate system of the tracker mount attached to the endoscope to the coordinate system of the endoscope camera), and determines radial lens distortion. The calibration routine is fast, automatic, accurate and reliable, and is insensitive to rotational orientation of the endoscope. The routine automatically detects, localizes, and identifies dots in a video image snapshot of the calibration target grid and determines the calibration parameters from the sets of known physical coordinates and localized image coordinates of the target grid dots. Using nonlinear lens-distortion correction, which can be performed at real-time rates (30 frames per second), the mean projection error is less than 0.5 mm at distances up to 25 mm from the endoscope tip, and less than 1.0 mm up to 45 mm. Experimental measurements and point-based registration error theory show that the tracking error is about 0.5-0.7 mm at the tip of the endoscope and less than 0.9 mm for all points in the field of view of the endoscope camera at a distance of up to 65 mm from the tip. It is probable that much of the projection error is due to endoscope tracking error rather than calibration error. Two examples of clinical applications are presented to illustrate the usefulness of image-enhanced endoscopy. This method is a useful addition to conventional image-guidance systems, which generally show only the position of the tip (and sometimes the orientation) of a surgical instrument or probe on reformatted image slices.