Early major fracture care in polytrauma-priorities in the context of concomitant injuries: A Delphi consensus process and systematic review.

BACKGROUND: The timing of major fracture care in polytrauma patients has a relevant impact on outcomes. Yet, standardized treatment strategies with respect to concomitant injuries are rare. This study aims to provide expert recommendations regarding the timing of major fracture care in the presence of concomitant injuries to the brain, thorax, abdomen, spine/spinal cord, and vasculature, as well as multiple fractures. METHODS: This study used the Delphi method supported by a systematic review. The review was conducted in the Medline and EMBASE databases to identify relevant literature on the timing of fracture care for patients with the aforementioned injury patterns. Then, consensus statements were developed by 17 international multidisciplinary experts based on the available evidence. The statements underwent repeated adjustments in online- and in-person meetings and were finally voted on. An agreement of ≥75% was set as the threshold for consensus. The level of evidence of the identified publications was rated using the GRADE approach. RESULTS: A total of 12,476 publications were identified, and 73 were included. The majority of publications recommended early surgery (47/73). The threshold for early surgery was set within 24 hours in 45 publications. The expert panel developed 20 consensus statements and consensus >90% was achieved for all, with 15 reaching 100%. These statements define conditions and exceptions for early definitive fracture care in the presence of traumatic brain injury (n = 5), abdominal trauma (n = 4), thoracic trauma (n = 3), multiple extremity fractures (n = 3), spinal (cord) injuries (n = 3), and vascular injuries (n = 2). CONCLUSION: A total of 20 statements were developed on the timing of fracture fixation in patients with associated injuries. All statements agree that major fracture care should be initiated within 24 hours of admission and completed within that timeframe unless the clinical status or severe associated issues prevent the patient from going to the operating room. LEVEL OF EVIDENCE: Delphi-Consensus/Systematic Review; Level IV.

Neurofeedback-enabled beta power control with a fully implanted DBS system in patients with Parkinson's disease.

OBJECTIVE: Parkinsonian motor symptoms are linked to pathologically increased beta oscillations in the basal ganglia. Studies with externalised deep brain stimulation electrodes showed that Parkinson patients were able to rapidly gain control over these pathological basal ganglia signals through neurofeedback. Studies with fully implanted deep brain stimulation systems duplicating these promising results are required to grant transferability to daily application. METHODS: In this study, seven patients with idiopathic Parkinson's disease and one with familial Parkinson's disease were included. In a postoperative setting, beta oscillations from the subthalamic nucleus were recorded with a fully implanted deep brain stimulation system and converted to a real-time visual feedback signal. Participants were instructed to perform bidirectional neurofeedback tasks with the aim to modulate these oscillations. RESULTS: While receiving regular medication and deep brain stimulation, participants were able to significantly improve their neurofeedback ability and achieved a significant decrease of subthalamic beta power (median reduction of 31% in the final neurofeedback block). CONCLUSION: We could demonstrate that a fully implanted deep brain stimulation system can provide visual neurofeedback enabling patients with Parkinson's disease to rapidly control pathological subthalamic beta oscillations. SIGNIFICANCE: Fully-implanted DBS electrode-guided neurofeedback is feasible and can now be explored over extended timespans.

Toward the "Perfect" Shunt: Historical Vignette, Current Efforts, and Future Directions.

As a concept, drainage of excess fluid volume in the cranium has been around for more than 1000 years. Starting with the original decompression-trepanation of Abulcasis to modern programmable shunt systems, to other nonshunt-based treatments such as endoscopic third ventriculostomy and choroid plexus cauterization, we have come far as a field. However, there are still fundamental limitations that shunts have yet to overcome: namely posture-induced over- and underdrainage, the continual need for valve opening pressure especially in pediatric cases, and the failure to reinstall physiologic intracranial pressure dynamics. However, there are groups worldwide, in the clinic, in industry, and in academia, that are trying to ameliorate the current state of the technology within hydrocephalus treatment. This chapter aims to provide a historical overview of hydrocephalus, current challenges in shunt design, what members of the community have done and continue to do to address these challenges, and finally, a definition of the "perfect" shunt is provided and how the authors are working toward it.

A Soft Robotic Actuator System for In Vivo Modeling of Normal Pressure Hydrocephalus.

OBJECTIVE: The intracranial pressure (ICP) affects the dynamics of cerebrospinal fluid (CSF) and its waveform contains information that is of clinical importance in medical conditions such as hydrocephalus. Active manipulation of the ICP waveform could enable the investigation of pathophysiological processes altering CSF dynamics and driving hydrocephalus. METHODS: A soft robotic actuator system for intracranial pulse pressure amplification was developed to model normal pressure hydrocephalus in vivo. Different end actuators were designed for intraventricular implantation and manufactured by applying cyclic tensile loading on soft rubber tubing. Their mechanical properties were investigated, and the type that achieved the greatest pulse pressure amplification in an in vitro simulator of CSF dynamics was selected for application in vivo. A hydraulic actuation device based on a linear voice coil motor was developed to enable automated and fast operation of the end actuators. The combined system was validated in an acute ovine pilot in vivo study. RESULTS: in vitro results show that variations in the used materials and manufacturing settings altered the end actuator's dynamic properties, such as the pressure-volume characteristics. In the in vivo model, a cardiac-gated actuation volume of 0.125 mL at a heart rate of 62 bpm caused an increase of 205% in mean peak-to-peak amplitude but only an increase of 1.3% in mean ICP. CONCLUSION: The introduced soft robotic actuator system is capable of ICP waveform manipulation. SIGNIFICANCE: Continuous amplification of the intracranial pulse pressure could enable in vivo modeling of normal pressure hydrocephalus and shunt system testing under pathophysiological conditions to improve therapy for hydrocephalus.

Impact of target depth on safety and efficacy outcomes in MR-guided focused ultrasound thalamotomy for tremor patients.

OBJECTIVE: Target depth, defined by the z-coordinate in the dorsoventral axis relative to the anterior commissure-posterior commissure axial plane of the MR-guided focused ultrasound (MRgFUS) lesion, is considered to be critical for tremor improvement and the occurrence of side effects such as gait impairment. However, although different z-coordinates are used in the literature, there are no comparative studies available with information on optimal lesion placement. This study aimed to compare two different MRgFUS lesion targets (z = +2 mm vs z = 0 mm) regarding efficacy and safety outcomes. METHODS: The authors conducted a retrospective analysis of 52 patients with pharmacoresistant tremor disorders who received unilateral MRgFUS thalamotomy in the ventral intermediate nucleus for the first time between 2017 and 2022 by one neurosurgeon, with two different z-coordinates, either z = +2 mm (+2-mm group; n = 17) or z = 0 mm (0-mm group; n = 35), but otherwise identical parameters. Standardized video-recorded assessments of efficacy (including the Washington Heights-Inwood Genetic Study of Essential Tremor scale) and safety (using a standardized grading system) outcomes at baseline and at 6 months posttreatment were reviewed and compared. Moreover, overall patient satisfaction was extracted as documented by the examiner at 6 months. RESULTS: Based on a multiple logistic regression analysis, the authors found that a more dorsal target with a z-coordinate of +2 mm as compared with 0 mm was associated with a higher incidence of any persistent side effect at 6 months (p = 0.02). Most consistently, sensory disturbances, although mild and nondisturbing in most cases, occurred more frequently in the +2-mm group (35% vs 11%, p = 0.007), while no significant differences were found for gait impairment (29% vs 35%) and arm ataxia (24% vs 11%). On the other hand, average tremor suppression was similar (63.6% vs 60.2%) between the groups. Here, higher efficacy was associated with a higher side effect burden in the 0-mm group but not in the +2-mm group. Despite the occurrence of side effects, general patient satisfaction was high (87% would undergo MRgFUS again) as most patients valued tremor suppression more. CONCLUSIONS: A more ventral MRgFUS target of z = 0 mm seems to be associated with a more favorable safety and a comparable efficacy profile as compared with a more dorsal target of z = +2 mm, but prospective studies are warranted.

The influence of upright posture on craniospinal, arteriovenous, and abdominal pressures in a chronic ovine in-vivo trial.

INTRODUCTION: Most investigations into postural influences on craniospinal and adjacent physiology have been performed in anesthetized animals. A comprehensive study evaluating these physiologies while awake has yet been completed. METHODS: Six awake sheep had telemetric pressure sensors (100 Hz) implanted to measure intracranial, intrathecal, arterial, central venous, cranial, caudal, dorsal, and ventral intra-abdominal pressure (ICP, ITP, ABP, CVP, IAPcr, IAPcd, IAPds, IAPve, respectively). They were maneuvered upright by placing in a chair for two minutes; repeated 25 times over one month. Changes in mean and pulse pressure were calculated by comparing pre-chair, P0, with three phases during the maneuver: P1, chair entrance; P2, chair halftime; P3, prior to chair exit. Statistical significance (p ≤ .05) was assessed using repeated measures ANOVA. RESULTS: Significant mean pressure changes of (P1 - P0) and (P3 - P0) were measured at - 12.1 ± 3.1 and - 14.2 ± 3.0(p < .001), 40.8 ± 10.5 and 37.7 ± 3.5(p = .019), 9.7 ± 8.3 and 6.2 ± 5.3(p = .012), 22.3 ± 29.8 and 12.5 ± 12.1(p = .042), and 11.7 ± 3.9 and 9.0 ± 5.2(p = .014) mmHg, for ICP, ITP, IAPds, IAPcr, IAPca, respectively. For pulse pressures, significant changes of (P1 - P0) and (P3 - P0) were measured at - 1.3 ± 0.7 and - 2.0 ± 1.1(p < .001), 4.7 ± 2.3 and 1.4 ± 1.4(p < .001), 15.0 ± 10.2 and 7.3 ± 5.5(p < .001), - 0.7 ± 1.8 and - 1.7 ± 1.7(p < .001), - 1.3 ± 4.2 and - 1.4 ± 4.7(p = .006), and 0.3 ± 3.9 and - 1.0 ± 1.3(p < .001) mmHg, for ICP, ITP, ABP, IAPds, IAPcr, IAPca, respectively. CONCLUSIONS: Pressures changed posture-dependently to differing extents. Changes were most pronounced immediately after entering upright posture (P1) and became less prominent over the chair duration (P2-to-P3), suggesting increased physiologic compensation. Dynamic changes in IAP varied across abdominal locations, motivating the abdominal cavity not to be considered as a unified entity, but sub-compartments with individual dynamics.

Influence of head-over-body and body-over-head posture on craniospinal, vascular, and abdominal pressures in an acute ovine in-vivo model.

INTRODUCTION: Optimal shunt-based hydrocephalus treatments are heavily influenced by dynamic pressure behaviors between proximal and distal ends of shunt catheters. Posture-dependent craniospinal, arterial, venous, and abdominal dynamics thereby play an essential role. METHODS: An in-vivo ovine trial (n = 6) was conducted to evaluate communication between craniospinal, arterial, venous, and abdominal dynamics. Tilt-testing was performed between -13° and + 13° at 10-min intervals starting and ending at 0° prone position. Mean pressure, pulse pressure, and Pearson correlation (r) to the respective angle were calculated. Correlations are defined as strong: |r|≥ 0.7, mild: 0.3 <|r|< 0.7, and weak: |r|≤ 0.3. Transfer functions (TFs) between the arterial and adjacent compartments were derived. RESULTS: Strong correlations were observed between posture and: mean carotid/femoral arterial (r = - 0.97, r = - 0.87), intracranial, intrathecal (r = - 0.98, r = 0.94), jugular (r = - 0.95), abdominal cranial, dorsal, caudal, and intravesical pressure (r = - 0.83, r = 0.84, r = - 0.73, r = 0.99) while mildly positive correlation exists between tilt and central venous pressure (r = 0.65). Only dorsal abdominal pulse pressure yielded a significant correlation to tilt (r = 0.21). TFs followed general lowpass behaviors with resonant peaks at 4.2 ± 0.4 and 11.5 ± 1.5 Hz followed by a mean roll-off of - 15.9 ± 6.0 dB/decade. CONCLUSIONS: Tilt-tests with multi-compartmental recordings help elucidate craniospinal, arterial, venous, and abdominal dynamics, which is essential to optimize shunt-based therapy. Results motivate hydrostatic influences on mean pressure, with all pressures correlating to posture, with little influence on pulse pressure. TF results quantify the craniospinal, arterial, venous, and abdominal compartments as compliant systems and help pave the road for better quantitative models of the interaction between the craniospinal and adjacent spaces.

Laser interstitial thermal therapy in pediatric cerebellar epilepsy.

Cerebellar lesional epilepsy is rare, commonly manifesting in early life and posing diagnostic and treatment challenges. Seizure semiology may be subtle, with repetitive eye blinking, face twitching, and irregular breathing, while EEG commonly remains unremarkable. Pharmacoresistance is the rule, and surgical intervention is the only treatment with the potential for cure. Novel minimally invasive techniques, such as laser interstitial thermal therapy (LITT), are emerging for surgically less accessible, deep-seated epileptogenic lesions. We report the case of a patient who presented with peculiar eye and face movements occurring episodically and stereotypically since the first weeks of life and was later diagnosed with cerebellar epilepsy related to a hamartoma. Refractory daily seizures, unresponsive to antiseizure medication, were followed by increasingly prominent gait ataxia and delayed speech development. Staged LITT was performed in two consecutive sessions at 3 and 4 years, leading to seizure cessation, neurological improvement, and developmental gains over a postsurgical follow-up period of 8 months. Our case highlights cerebellar lesional epilepsy as a rare but important differential diagnosis in children with paroxysmal disorders predominantly involving the face. Furthermore, we illustrate the radiological correlates of neurocognitive deficit related to the cerebellar lesion, manifesting as cerebello-cerebral diaschisis. Most importantly, our observations showcase LITT as a safe and effective therapeutic approach in cerebellar lesional epilepsy and an attractive alternative to open brain surgery, especially for deep-seated lesions in the pediatric population.

Gait pattern analysis in the home environment as a key factor for the reliable assessment of shunt responsiveness in patients with idiopathic normal pressure hydrocephalus.

Background: The identification of patients with gait disturbance associated with idiopathic normal pressure hydrocephalus (iNPH) is challenging. This is due to the multifactorial causes of gait disturbance in elderly people and the single moment examination of laboratory tests. Objective: We aimed to assess whether the use of gait sensors in a patient's home environment could help establish a reliable diagnostic tool to identify patients with iNPH by differentiating them from elderly healthy controls (EHC). Methods: Five wearable inertial measurement units were used in 11 patients with iNPH and 20 matched EHCs. Data were collected in the home environment for 72 h. Fifteen spatio-temporal gait parameters were analyzed. Patients were examined preoperatively and postoperatively. We performed an iNPH sub-group analysis to assess differences between responders vs. non-responders. We aimed to identify parameters that are able to predict a reliable response to VP-shunt placement. Results: Nine gait parameters significantly differ between EHC and patients with iNPH preoperatively. Postoperatively, patients with iNPH showed an improvement in the swing phase (p = 0.042), and compared to the EHC group, there was no significant difference regarding the cadence and traveled arm distance. Patients with a good VP-shunt response (NPH recovery rate of ≥5) significantly differ from the non-responders regarding cycle time, cycle time deviation, number of steps, gait velocity, straight length, stance phase, and stance to swing ratio. A receiver operating characteristic analysis showed good sensitivity for a preoperative stride length of ≥0.44 m and gait velocity of ≥0.39 m/s. Conclusion: There was a significant difference in 60% of the analyzed gait parameters between EHC and patients with iNPH, with a clear improvement toward the normalization of the cadence and traveled arm distance postoperatively, and a clear improvement of the swing phase. Patients with iNPH with a good response to VP-shunt significantly differ from the non-responders with an ameliorated gait pattern.

Venous dynamics in anesthetized sheep govern postural-induced changes in cerebrospinal fluid pressure comparable to those in humans.

Sheep are popular large animals in which to model human disorders and to study physiological processes such as cerebrospinal fluid dynamics. However, little is known about vascular compensatory mechanisms affecting cerebrospinal fluid pressures during acute postural changes in sheep. Six female white Alpine sheep were anesthetized to investigate the interactions of the vascular and cerebrospinal fluid system by acquiring measurements of intracranial pressure and central and jugular venous pressure during passive postural changes induced by a tilt table. The cross-sectional area of the common jugular vein and venous blood flow velocity was recorded. Anesthetized sheep showed bi-phasic effects of postural changes on intracranial pressure during tilting. A marked collapse of the jugular vein was observed during head-over-body tilting; this is in accordance with findings in humans. Active regulatory effects of the arterial system on maintaining cerebral perfusion pressure were observed independent of tilting direction. Conclusion: Anesthetized sheep show venous dynamics in response to posture-induced changes in intracranial pressure that are comparable with those in humans.

[Trigeminal Neuralgia - What Do We Know about the Causes, Diagnosis and Treatment?] / Trigeminusneuralgie ­ was wissen wir über die Ursachen, Diagnostik und Therapie?

Trigeminal Neuralgia - What Do We Know about the Causes, Diagnosis and Treatment? Abstract. Classical trigeminal neuralgia is typically characterized by a stimulus-evoked, recurrent and intense short-lasting stabbing pain in the innervation area of the trigeminal nerve. Its intensity is among the most severe pain imaginable in humans, and yet it is often misdiagnosed and undertreated. Triggers are common activities of daily life like talking or eating. The classical trigeminal neuralgia is due to a neurovascular compression at the nerve root entry zone. The secondary form is related to an underlying neurological disease (caused for example by multiple sclerosis or compression by a brain tumor); the etiology of the idiopathic trigeminal neuralgia is unknown. Treatment options include both medication (mostly antiepileptic drugs) and escalated interventional approaches (microvascular decompression, neurolesional percutaneous procedures, neuromodulative therapeutic options and radiosurgery).

Nicotine Replacement Therapy for Smokers with Acute Aneurysmal Subarachnoid Hemorrhage: An International Survey.

INTRODUCTION: Smoking prevalence is twice as high among patients admitted to hospital because of the acute condition of aneurysmal subarachnoid hemorrhage (aSAH) as in the general population. Smoking cessation may improve the prognosis of aSAH, but nicotine replacement therapy (NRT) administered at the time of aSAH remains controversial because of potential adverse effects such as cerebral vasospasm. We investigated the international practice of NRT use for aSAH among neurosurgeons. METHODS: The online SurveyMonkey software was used to administer a 15-question, 5-min online questionnaire. An invitation link was sent to those 1425 of 1988 members of the European Association of Neurosurgical Societies (EANS) who agreed to participate in surveys to assess treatment strategies for withdrawal of tobacco smoking during aSAH. Factors contributing to physicians' posture towards NRT were assessed. RESULTS: A total of 158 physicians from 50 nations participated in the survey (response rate 11.1%); 68.4% (108) were affiliated with university hospitals and 67.7% (107) practiced at high-volume neurovascular centers with at least 30 treated aSAH cases per year. Overall, 55.7% (88) of physicians offered NRT to smokers with aSAH, 22.1% (35) offered non-NRT support including non-nicotine medication and counselling, while the remaining 22.1% (35) did not actively support smoking cessation. When smoking was not possible, 42.4% (67) of physicians expected better clinical outcomes when prescribing NRT instead of nicotine deprivation, 36.1% (57) were uncertain, 13.9% (22) assumed unaffected outcomes, and 7.6% (12) assumed worse outcomes. Only 22.8% (36) physicians had access to a local smoking cessation team in their practice, of whom half expected better outcomes with NRT as compared to deprivation. CONCLUSIONS: A small majority of the surveyed physicians of the EANS offered NRT to support smoking cessation in hospitalized patients with aSAH. However, less than half believed that NRT could positively impact clinical outcome as compared to deprivation. This survey demonstrated the lack of consensus regarding use of NRT for hospitalized smokers with aSAH.

The modulatory effect of self-paced and cued motor execution on subthalamic beta-bursts in Parkinson's disease: Evidence from deep brain recordings in humans.

Deep brain stimulation (DBS) electrodes provide an unparalleled window to record and investigate neuronal activity right at the core of pathological brain circuits. In Parkinson's disease (PD), basal ganglia beta-oscillatory activity (13-35 Hz) seems to play an outstanding role. Conventional DBS, which globally suppresses beta-activity, does not meet the requirements of a targeted treatment approach given the intricate interplay of physiological and pathological effects of beta-frequencies. Here, we wanted to characterise the local field potential (LFP) in the subthalamic nucleus (STN) in terms of beta-burst prevalence, amplitude and length between movement and rest as well as during self-paced as compared to goal-directed motor control. Our electrophysiological recordings from externalised DBS-electrodes in nine patients with PD showed a marked decrease in beta-burst durations and prevalence during movement as compared to rest as well as shorter and less frequent beta-bursts during cued as compared to self-paced movements. These results underline the importance of beta-burst modulation in movement generation and are in line with the clinical observation that cued motor control is better preserved than self-paced movements. Furthermore, our findings motivate the use of adaptive DBS based on beta-bursts, which selectively trim longer beta-bursts, as it is more suitable and efficient over a range of motor behaviours than conventional DBS.

Bilateral Focused Ultrasound Pallidotomy for Parkinson-Related Facial Dyskinesia-A Case Report.

Background: For safety reasons, both magnetic resonance-guided high-intensity focused ultrasound (MRgHiFUS) thalamotomy and pallidotomy are currently approved exclusively for unilateral treatment, but axial symptoms like levodopa-induced orofacial dyskinesia require a bilateral approach. Objectives: We report the first case of successful bilateral MRgHiFUS pallidotomy for peak-dose dyskinesia in a patient with Parkinson's disease (PD). Methods: The treatment decision was based on the patient's reluctance toward brain implants and pump therapies and the fact that he had limited access to a deep brain stimulation center in his home country. The treatment was planned as staged procedure with an interval of 18 months because of travel restrictions because of the coronavirus disease (COVID)-19 pandemic. Results: After the second treatment, levodopa-induced orofacial dyskinesia remitted and improved bradykinesia and rigidity with stable gait and good postural reflexes. Conclusions: This promising result suggests that in selected PD patients with dyskinesia, staged bilateral MRgHiFUS pallidotomy might be considered.

Air travel with pneumocephalus: a systematic review.

INTRODUCTION: Concerns arise when patients with pneumocephalus engage in air travel. How hypobaric cabin pressure affects intracranial air is largely unclear. A widespread concern is that the intracranial volume could relevantly expand during flight and lead to elevated intracranial pressure. The aim of this systematic review was to identify and summarise models and case reports with confirmed pre-flight pneumocephalus. METHODS: The terms (pneumocephalus OR intracranial air) AND (flying OR fly OR travel OR air transport OR aircraft) were used to search the database PubMed on 30 November 2021. This search returned 144 results. To be included, a paper needed to fulfil each of the following criteria: (i) peer-reviewed publication of case reports, surveys, simulations or laboratory experiments that focussed on air travel with pre-existing pneumocephalus; (ii) available in full text. RESULTS: Thirteen studies met the inclusion criteria after title or abstract screening. We additionally identified five more articles when reviewing the references. A notion that repeatedly surfaced is that any air contained within the neurocranium increases in volume at higher altitude, much like any extracranial gas, potentially resulting in tension pneumocephalus or increased intracranial pressure. DISCUSSION: Relatively conservative thresholds for patients flying with pneumocephalus are suggested based on models where the intracranial air equilibrates with cabin pressure, although intracranial air in a confined space would be surrounded by the intracranial pressure. There is a discrepancy between the models and case presentations in that we found no reports of permanent or transient decompensation secondary to a pre-existing pneumocephalus during air travel. Nevertheless, the quality of examination varies and clinicians might tend to refrain from reporting adverse events. We identified a persistent extracranial to intracranial fistulous process in multiple cases with newly diagnosed pneumocephalus after flight. Finally, we summarised management principles to avoid complications from pneumocephalus during air travel and argue that a patient-specific understanding of the pathophysiology and time course of the pneumocephalus are potentially more important than its volume.

The Sheep as a Comprehensive Animal Model to Investigate Interdependent Physiological Pressure Propagation and Multiparameter Influence on Cerebrospinal Fluid Dynamics.

The present study aims to develop a suitable animal model for evaluating the physiological interactions between cerebrospinal fluid (CSF) dynamics, hemodynamics, and abdominal compartment pressures. We seek to contribute to the enhanced recognition of the pathophysiology of CSF-dependent neurological disorders like hydrocephalus and the improvement of available treatment options. To date, no comprehensive animal model of CSF dynamics exists, and establishing an accurate model will advance our understanding of complex CSF physiology. Persisting knowledge gaps surrounding the communication and pressure propagation between the cerebrospinal space and adjacent anatomical compartments exacerbate the development of novel therapies for neurological diseases. Hence, the need for further investigation of the interactions of vascular, craniospinal, and abdominal pressures remains beyond dispute. Moreover, the results of this animal study support the optimization of in vitro test benches for medical device development, e.g., ventriculoperitoneal shunts. Six female white alpine sheep were surgically equipped with pressure sensors to investigate the physiological values of intracranial, intrathecal, arterial, central venous, jugular venous, vesical pressure, and four differently located abdominal pressures. These values were measured simultaneously during the acute animal trial with sheep under general anesthesia. Both carotid and femoral arterial blood pressure indicate a reliable and comparable representation of the systematic blood pressure. However, the jugular venous pressure and the central venous pressure in sheep in dorsal recumbency do not correlate well under general anesthesia. Furthermore, there is a trend for possible comparability of lateral intraventricular and lumbar intrathecal pressure. Nevertheless, animal body position during measurements must be considered since different body constitutions can alter the horizontal line between the cerebral ventricles and the lumbar subarachnoid space. While intra-abdominal pressure measurement in the four different abdominal quadrants yielded greater inter-individual variability, intra-vesical pressure measurements in our setting delivered comparable values for all sheep. We established a novel and comprehensive ovine animal model to investigate interdependent physiologic pressure propagation and multiparameter influences on CSF dynamics. The results of this study will contribute to further in vitro bench testing, the derivation of novel quantitative models, and the development of a pathologic ovine hydrocephalus model.

Inhaled Nitric Oxide Treatment for Aneurysmal SAH Patients With Delayed Cerebral Ischemia.

BACKGROUND: We demonstrated experimentally that inhaled nitric oxide (iNO) dilates hypoperfused arterioles, increases tissue perfusion, and improves neurological outcome following subarachnoid hemorrhage (SAH) in mice. We performed a prospective pilot study to evaluate iNO in patients with delayed cerebral ischemia after SAH. METHODS: SAH patients with delayed cerebral ischemia and hypoperfusion despite conservative treatment were included. iNO was administered at a maximum dose of 40 ppm. The response to iNO was considered positive if: cerebral artery diameter increased by 10% in digital subtraction angiography (DSA), or tissue oxygen partial pressure (PtiO2) increased by > 5 mmHg, or transcranial doppler (TCD) values decreased more than 30 cm/sec, or mean transit time (MTT) decreased below 6.5 secs in CT perfusion (CTP). Patient outcome was assessed at 6 months with the modified Rankin Scale (mRS). RESULTS: Seven patients were enrolled between February 2013 and September 2016. Median duration of iNO administration was 23 h. The primary endpoint was reached in all patients (five out of 17 DSA examinations, 19 out of 29 PtiO2 time points, nine out of 26 TCD examinations, three out of five CTP examinations). No adverse events necessitating the cessation of iNO were observed. At 6 months, three patients presented with a mRS score of 0, one patient each with an mRS score of 2 and 3, and two patients had died. CONCLUSION: Administration of iNO in SAH patients is safe. These results call for a larger prospective evaluation.

Intercompartmental communication between the cerebrospinal and adjacent spaces during intrathecal infusions in an acute ovine in-vivo model.

INTRODUCTION: The treatment of hydrocephalus has been a topic of intense research ever since the first clinically successful use of a valved cerebrospinal fluid shunt 72 years ago. While ample studies elucidating different phenomena impacting this treatment exist, there are still gaps to be filled. Specifically, how intracranial, intrathecal, arterial, and venous pressures react and communicate with each other simultaneously. METHODS: An in-vivo sheep trial (n = 6) was conducted to evaluate and quantify the communication existing within the cranio-spinal, arterial, and venous systems (1 kHz sampling frequency). Standardized intrathecal infusion testing was performed using an automated infusion apparatus, including bolus and constant pressure infusions. Bolus infusions entailed six lumbar intrathecal infusions of 2 mL Ringer's solution. Constant pressure infusions were comprised of six regulated pressure steps of 3.75 mmHg for periods of 7 min each. Mean pressure reactions, pulse amplitude reactions, and outflow resistance were calculated. RESULTS: All sheep showed intracranial pressure reactions to acute increases of intrathecal pressure, with four of six sheep showing clear cranio-spinal communication. During bolus infusions, the increases of mean pressure for intrathecal, intracranial, arterial, and venous pressure were 16.6 ± 0.9, 15.4 ± 0.8, 3.9 ± 0.8, and 0.1 ± 0.2 mmHg with corresponding pulse amplitude increases of 2.4 ± 0.3, 1.3 ± 0.3, 1.3 ± 0.3, and 0.2 ± 0.1 mmHg, respectively. During constant pressure infusions, mean increases from baseline were 14.6 ± 3.8, 15.5 ± 4.2, 4.2 ± 8.2, and 3.2 ± 2.4 mmHg with the corresponding pulse amplitude increases of 2.5 ± 3.6, 2.5 ± 3.0, 7.7 ± 4.3, and 0.7 ± 2.0 mmHg for intrathecal, intracranial, arterial, and venous pulse amplitude, respectively. Outflow resistances were calculated as 51.6 ± 7.8 and 77.8 ± 14.5 mmHg/mL/min for the bolus and constant pressure infusion methods, respectively-showing deviations between the two estimation methods. CONCLUSIONS: Standardized infusion tests with multi-compartmental pressure recordings in sheep have helped capture distinct reactions between the intrathecal, intracranial, arterial, and venous systems. Volumetric pressure changes in the intrathecal space have been shown to propagate to the intraventricular and arterial systems in our sample, and to the venous side in individual cases. These results represent an important step into achieving a more complete quantitative understanding of how an acute rise in intrathecal pressure can propagate and influence other systems.