Serum Biomarkers for Risk Assessment of Intrahospital Transports in Mechanically Ventilated Neurosurgical Intensive Care Unit Patients.

OBJECTIVE: Intrahospital transports (IHTs) of neurosurgical intensive care unit (NICU) patients can be hazardous. Increasing intracranial pressure (ICP) and/or decreasing cerebral perfusion pressure (CPP) as well as cardiopulmonary alterations are common complications of an IHTs, which can lead to secondary brain injury. This study was performed to assess several serum biomarkers concerning their potential to improve safety of IHTs in mechanically ventilated NICU patients. METHODS: All IHTs of mechanically ventilated and sedated NICU patients from 03/2017 to 01/2018 were retrospectively analyzed. Intracranial pressure and CPP measurements were performed in all patients. Serum hemoglobin, hematocrit, and serum sodium were defined as serum biomarkers. Demographic data, computed tomography scan on admission, Simplified Acute Physiology Score and Acute Physiology and Chronic Health Evaluation II, modified Rankin Scale, indication and consequence of IHTs were analyzed. Alteration of ICP/CPP, hemodynamic and pulmonary events were defined as complications. The study population was stratified into patients with the occurrence of a complication and absence of a complication. RESULTS: We analyzed a total number of 184 IHTs in 70 NICU patients with an overall complication rate of 57.6%. Of all, 32.1% IHTs had no direct therapeutic consequence. In patients with higher hemoglobin values prior to IHT less complications occurred, concerning ICP (P = .001), CPP (P = .001), hemodynamic (P = .005), and pulmonary (P < .0001) events. In addition, complications concerning ICP (P = .001), CPP (P = .001), hemodynamic (P = .005), and pulmonary problems (P = .002) were significantly lower in patients with higher hematocrit values before IHT. CONCLUSION: Intrahospital transports of mechanically ventilated NICU patients carry a high risk of increased ICP and hemodynamic complications and should be performed restrictively. Higher values of hemoglobin and hematocrit prior to IHT were associated with less complications with regard to ICP, CPP as well as hemodynamic and pulmonary events and could be helpful to assess the potential risk of complications prior to IHTs.

Microvasospasms After Experimental Subarachnoid Hemorrhage Do Not Depend on Endothelin A Receptors.

BACKGROUND AND PURPOSE: Perturbations in cerebral microcirculation (eg, microvasospasms) and reduced neurovascular communication determine outcome after subarachnoid hemorrhage (SAH). ET-1 (endothelin-1) and its receptors have been implicated in the pathophysiology of large artery spasms after SAH; however, their role in the development of microvascular dysfunction is currently unknown. Here, we investigated whether inhibiting ETA (endothelin A) receptors can reduce microvasospasms after experimentally induced SAH. METHODS: SAH was induced in male C57BL/6 mice by filament perforation of the middle cerebral artery. Three hours after SAH, a cranial window was prepared and the pial and parenchymal cerebral microcirculation was measured in vivo using two-photon microscopy before, during, and after administration of the ETA receptor inhibitor clazosentan. In separate experiments, the effect of clazosentan treatment on neurological outcome was measured 3 days after SAH. RESULTS: Clazosentan treatment had no effect on the number or severity of SAH-induced cerebral microvasospasms nor did it affect neurological outcome. CONCLUSIONS: Our results indicate that ETA receptors, which mediate large artery spasms after SAH, do not seem to play a role in the development of microarterial spasms, suggesting that posthemorrhagic spasms are mediated by distinct mechanisms in large and small cerebral vessels. Given that cerebral microvessel dysfunction is a key factor for outcome after SAH, further research into the mechanisms that underlie posthemorrhagic microvasospasms is urgently needed.

Microsurgical unilateral laminotomy for decompression of lumbar spinal stenosis: long-term results and predictive factors.

BACKGROUND: The microsurgical unilateral laminotomy (MUL) technique for bilateral decompression of lumbar spinal stenosis (LSS) is a less destabilizing alternative to laminectomy and leads to good short-term outcomes. However, little is known about the long-term results including predictive factors. METHODS: Medical records of patients who underwent MUL for LSS decompression between 2005 and 2010 were reviewed, and a questionnaire was distributed to complement the long-term outcome data. The study population consisted of 176 patients including 17 patients with stable grade I spondylolisthesis. Complications and reoperations were meticulously analyzed. Clinical outcome was measured using a modified Prolo scale and was further dichotomized in good vs. poor outcome. Predictive factors were obtained from uni- and multivariate analyses. RESULTS: The median age of the cohort was 70.0 years and the follow-up 71.7 months. Complications occurred in 5.1 % of the patients. The overall reoperation rate was 17.0 %, including surgery, which was exclusively performed at other levels in 4.0 %. The reoperation rate for fusion was 4.5 %. Good neurogenic claudication outcome faded from 98.3 % at hospital discharge to 47.2 % at 6 years. Multivariate analysis identified previous lumbar operation as a potential independent predictor of a reoperation; potential independent predictors of poor long-term claudication outcome were older age, female gender, higher body mass index (BMI) and tobacco smoking. CONCLUSIONS: In our experience, the long-term reoperation rate after MUL for LSS is not negligible and higher in previously operated patients. It seems like the good initial clinical results after MUL may fade over time, and several patient-related predictive factors including potentially modifiable obesity and tobacco smoking seem to play an important role.

Microsurgical fenestration of idiopathic intramedullary cysts in adult patients.

PURPOSE: The aim of this study is to describe the findings in one of the largest series of microsurgically treated intramedullary cysts investigated by magnetic resonance imaging (MRI), focusing on the peri- and intraoperative setup including detailed neurological and radiological outcome analyses. METHODS: Retrospective analysis of patients with intramedullary cyst who had undergone microsurgical fenestration at our department between 2006 and 2011. Preoperative three-dimensional constructive interference of steady-state MRI was conducted to optimize surgical planning. Intraoperative electrophysiological monitoring included motor-evoked potentials, somatosensory-evoked potentials, and electromyogram. Clinical outcome as well as pre-, postoperative and long-term MRI scans were evaluated. RESULTS: Eight female patients (median age 58.0 years, range 32-72 years) with a median clinical follow-up of 48.0 months (range 2-69 months) were included. Seven cysts were located in the conus medullaris, one in the cervical spine. Overall, 25.0% (2/8) showed complete remission of preoperative symptoms, 62.5% (5/8) improved, and 12.5% (1/8) asymptomatic patients remained unchanged. Pain syndromes (4/4) as well as motor deficits (2/2) improved in all affected patients and bladder dysfunction (3/4) displayed a high tendency for improvement. Postoperative MRI scans showed permanently decreased cyst volumes by ~80%. CONCLUSION: Microsurgical fenestration of intramedullary cysts using preoperative high-resolution imaging and intraoperative electrophysiological monitoring is a safe and effective treatment option for symptomatic patients.

Structure of Neurosurgical Care in Germany in Comparison to Countries Organized in the European Association of Neurosurgical Societies: A Need to Reorganize Neurosurgical Training and Care in Germany.

BACKGROUND: Although the world is experiencing a deficit in the neurosurgical workforce, the number of neurosurgeons in Germany has increased within the last two decades. The aim of the present study was to assess the neurosurgical workforce in Germany, compare it to European countries, and assess structures in neurosurgical departments in Germany. METHODS: Data regarding the number of neurosurgeons in Germany as well as the number of departments, beds, cases, and neurosurgical procedures were gathered. A survey among German neurosurgical departments was performed to assess the structure of neurosurgical care. Furthermore, another survey among European countries was performed to acquire information regarding the number of surgeons and the regulation of training. RESULTS: From 2000 to 2019, the number of board-certified neurosurgeons in Germany increased by 151% from 973 to 2,446. During the same period, the German population increased by only 1% from 82.26 million to 83.17 million. Thus, the number of neurosurgeons per 100,000 inhabitants increased from 1.18 to 2.94. The increase of neurosurgeons is not paralleled by an increase in departments or an increase in neurosurgical procedures within the active neurosurgical departments. In comparison to the participating European countries, where the number of neurosurgeons per 100,000 inhabitants ranged from 0.45 to 2.94, with Germany shows the highest number. CONCLUSIONS: German institutions of medical administration urgently need to consider regulation of neurosurgical specialist training to prevent a further uncontrolled increase in neurosurgeons in a manner that is not adapted to the needs of neurosurgical care for the German population. Actions might include a regulation of entry to the training and of the number of training sites. Furthermore, an integration of non-physician assistant health care professionals and delegation of non-surgical workload from neurosurgeons is necessary. A further increase in neurosurgeons would be associated with a decrease in the surgical caseload per surgeons during training and after board certification, which might compromise the quality of neurosurgical care.

Vasopressin V(1a) receptors mediate posthemorrhagic systemic hypertension thereby determining rebleeding rate and outcome after experimental subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Arginine vasopressin V(1) receptors have been suggested to be involved in the pathophysiology of acute brain injury. Therefore, we aimed to determine the role of arginine vasopressin V(1) receptors after experimental subarachnoid hemorrhage (SAH). METHODS: Sprague-Dawley rats subjected to SAH by endovascular puncture received either vehicle or a V(1) receptor antagonist intravenously from 1 minute before until 3 hours after SAH. Intracranial pressure, cerebral blood flow, and mean arterial blood pressure were monitored until 60 minutes after SAH. Brain water content was quantified 24 hours after SAH and neurological function and mortality were assessed daily for 7 days after hemorrhage. RESULTS: In control rats, SAH induced high intracranial pressure, a brief increase in plasma arginine vasopressin, a subsequent increase in systemic blood pressure (Cushing response), a high rebleeding rate (30%), severe neurological deficits, and a 7-day mortality rate of 50%. V(1) receptor antagonist-treated animals exhibited a far less pronounced Cushing response, a less severe increase of intracranial pressure, did not exhibit rebleedings, had less severe brain edema formation and neurological deficits, and a mortality rate of only 20% (all P<0.05 versus vehicle). CONCLUSIONS: Inhibition of arginine vasopressin V(1a) receptors reduces the severity of SAH and prevents rebleedings by blunting the posthemorrhagic hypertonic response (Cushing reflex), thereby reducing mortality and secondary brain damage after experimental SAH. Because the severity of the initial bleeding and rebleedings are major factors contributing to an unfavorable outcome after SAH, inhibition of V(1a) receptors may represent a novel strategy to treat SAH.

The effects of lumbar fusion and non-fusion surgery on the development of Modic changes.

BACKGROUND: The aim of this study was to investigate the influence of lumbar fusion and non-fusion surgery on the postoperative development of Modic changes (MCs). METHODS: A total of 270 patients who underwent lumbar fusion, microsequestrectomy, microdiscectomy, and microdecompression, and who were examined by pre- and postoperative magnetic resonance imaging during the period of January 2012 to December 2018, were included in this retrospective study. The incidence of new postoperative MCs and the change of volume of preexisting MCs after surgery were investigated. RESULTS: The total incidence of new MCs following lumbar surgical procedures was 36.3%. Lumbar fusion showed a tendency towards a lower postoperative incidence of new MCs than the other three lumbar surgical procedures. The first postoperative year seems to be the most active phase for the development of new MCs. The postoperative volumes of MCs in patients who underwent lumbar non-fusion procedures were significantly greater than those before surgery (P < 0.01). However, no significant difference was detected between pre- and postoperative volumes of MCs in patients with lumbar fusion (P > 0.05). CONCLUSION: Lumbar surgical procedures contribute to the development of new MCs, particularly non-fusion surgeries. However, further studies are needed to confirm the clinical relevance of these findings.

Contribution of matrix metalloproteinase-9 to cerebral edema and functional outcome following experimental subarachnoid hemorrhage.

BACKGROUND: Cerebral edema is an important risk factor for death and poor outcome following subarachnoid hemorrhage (SAH). However, underlying mechanisms are still poorly understood. Matrix metalloproteinase (MMP)-9 is held responsible for the degradation of microvascular basal lamina proteins leading to blood-brain barrier dysfunction and, thus, formation of vasogenic cerebral edema. The current study was conducted to clarify the role of MMP-9 for the development of cerebral edema and for functional outcome after SAH. METHODS: SAH was induced in FVB/N wild-type (WT) or MMP-9 knockout (MMP-9(-/-)) mice by endovascular puncture. Intracranial pressure (ICP), regional cerebral blood flow (rCBF), and mean arterial blood pressure (MABP) were continuously monitored up to 30 min after SAH. Mortality was quantified for 7 days after SAH. In an additional series neurological function and body weight were assessed for 3 days after SAH. Subsequently, ICP and brain water content were quantified. RESULTS: Acute ICP, rCBF, and MABP did not differ between WT and MMP-9(-/-) mice, while 7 days' mortality was lower in MMP-9(-/-) mice (p = 0.03; 20 vs. 60%). MMP-9(-/-) mice also exhibited better neurological recovery, less brain edema formation, and lower chronic ICP. CONCLUSIONS: The results of the current study suggest that MMP-9 contributes to the development of early brain damage after SAH by promoting cerebral edema formation. Hence, MMP- 9 may represent a novel molecular target for the treatment of SAH.

Correlation of Modic Changes with Sagittal Lumbopelvic Parameters.

PURPOSE: The main aim of this retrospective study was to analyze lumbopelvic sagittal parameters among the three different types of Modic changes (MCs). Furthermore, correlations between the sizes of MCs and the number of involved lumbar levels with lumbopelvic parameters are investigated. METHODS: A total of 263 adult subjects with MCs at a single institution from September 2015 to October 2020 who underwent lumbar x-ray examinations and magnetic resonance imaging were included in this retrospective study. Types of MCs, sizes of MCs, lumbar levels involved by MCs as well as lumbopelvic sagittal parameters from each subject were evaluated by two authors. RESULTS: Lumbar lordosis (LL), sacral slope (SS), and pelvic incidence (PI) in subjects with MC grade 1 were significantly smaller than in those with MC grade 2 and grade 3 (p<0.05). Lumbopelvic sagittal parameters decreased significantly as the sizes aggravated (p<0.01). Triple lumbar levels with MCs showed a significant increase in PI-LL (p<0.05) and decrease in LL (p<0.01), SS (p<0.01), and PI (p<0.01) when compared to MCs at single and double lumbar levels. CONCLUSION: MC grade 1, severe MCs, and lumbar multi-segmental MCs were significantly linked to lumbar sagittal imbalance.

Diffusion Tensor Imaging for Surgical Planning in Patients with Cervical Spondylotic Myelopathy.

BACKGROUND AND STUDY AIMS/OBJECTIVE: Despite its invasiveness, computed tomography myelography (CTM) is still considered an important supplement to conventional magnetic resonance imaging (MRI) for preoperative evaluation of multilevel cervical spondylotic myelopathy (CSM). We analyzed if diffusion tensor imaging (DTI) could be a less invasive alternative for this purpose. MATERIAL AND METHODS: In 20 patients with CSM and an indication for decompression of at least one level, CTM was performed preoperatively to determine the extent of spinal canal/cerebrospinal fluid (CSF) space and cord compression (Naganawa score) for a decision on the number of levels to be decompressed. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were correlated with these parameters and with MRI-based increased signal intensity (ISI). Receiver operating characteristic analysis was performed to determine the sensitivity to discriminate levels requiring decompression surgery. European Myelopathy Score (EMS) and neck/radicular visual analog scale (VAS-N/R) were used for clinical evaluation. RESULTS: According to preoperative CTM, 20 levels of maximum and 16 levels of relevant additional stenosis were defined and decompressed. Preoperative FA and particularly ADC showed a significant correlation with the CTM Naganawa score but also with the ISI grade. Furthermore, both FA and ADC facilitated a good discrimination between stenotic and nonstenotic levels with cutoff values < 0.49 for FA and > 1.15 × 10-9 m2/s for ADC. FA and especially ADC revealed a considerably higher sensitivity (79% and 82%, respectively) in discriminating levels requiring decompression surgery compared with ISI (55%). EMS and VAS-N/R were significantly improved at 14 months compared with preoperative values. CONCLUSION: DTI parameters are highly sensitive at distinguishing surgical from nonsurgical levels in CSM patients and might therefore represent a less invasive alternative to CTM for surgical planning.

Troponin I as an early biomarker of cardiopulmonary parameters during the first 24 h of intensive care unit treatment in isolated traumatic brain injury patients.

OBJECTIVE: Cardiopulmonary (CP) complications are well-known phenomena after an isolated traumatic brain injury (iTBI) and they may be associated with an elevated serum troponin I (TnI) value. However, the influence of an elevated TnI level on CP parameters within the first 24 h after an iTBI is still unknown. The current study was conducted to assess the associations between the initial TnI value on admission and CP parameters during the first 24 h of intensive care unit (ICU) treatment in iTBI patients. PATIENTS AND METHODS: A total of 288 patients with iTBIs, who were admitted to our emergency department between January 2010 and November 2016 were retrospectively analyzed. Blood samples were taken on admission to determine TnI value. Each patient's demographic data, treatment regime, computed tomography results, and intra-hospital outcomes were evaluated, as well as several CP parameters, within the first 24 h of ICU treatment. The entire study population was stratified into patients with an initial TnI elevation (TnI positive) and without an initial TnI elevation (TnI negative). RESULTS: Increased TnI values on admission were found in 59 (20.5%) patients. There were significant correlations between an initially elevated TnI value and a lower Glasgow Coma Scale score (p = 0.003), higher head Abbreviated Injury Scale score (p<0.0001), and higher Acute Physiology and Chronic Health Evaluation II score (p = 0.005) on admission, as well as a lower Glasgow Outcome Scale score (p = 0.0002) and higher modified Rankin Scale score (p = 0.0001) at discharge. In addition, a significantly higher norepinephrine application rate (NAR) (p<0.0001) and inspiratory oxygen fraction (FiO2) (p = 0.028) were needed in the TnI positive group. CONCLUSION: Patients with elevated TnI values on admission require more circulation support (NAR and FiO2) within the first 24 h of ICU treatment after an iTBI. Therefore, the TnI may be a useful biomarker to improve ICU treatment of these patients.

Implementation of Transforaminal Endoscopic Lumbar Sequestrectomy in a German University Hospital Setting: A Long and Rocky Road.

OBJECTIVE: Microsurgical diskectomy/sequestrectomy is the standard procedure for the surgical treatment of lumbar disk herniations. The transforaminal endoscopic sequestrectomy technique is a minimally invasive alternative with potential advantages such as minimal blood loss and tissue damage, as well as early mobilization of the patient. We report the implementation of this technique in a German university hospital setting. METHODS: One single surgeon performed transforaminal endoscopic sequestrectomy from February 2013 to July 2016 for lumbar disk herniation in 44 patients. Demographic as well as perioperative, clinical, and radiologic data were analyzed from electronic records. Furthermore, we investigated complications, intraoperative change of the procedure to microsurgery, and reoperations. The postoperative course was analyzed using the Macnab criteria, supplemented by a questionnaire for follow-up. Pre- and postoperative magnetic resonance imaging volumetric analyses were performed to assess the radiologic efficacy of the technique. RESULTS: Our study population had a median age of 52 years. The median follow-up was 15 months, and the median length of hospital stay was 4 days. Median duration of surgery was 100 minutes with a median blood loss of 50 mL. Surgery was most commonly performed at the L4-L5 level (63%) and in caudally migrated disk herniations (44%). In six patients, surgery was performed for recurrent disk herniations. The procedure had to be changed to conventional microsurgery in four patients. We observed no major complications. Minor complications occurred in six patients, and in four patients a reoperation was performed. Furthermore, a significantly lower Oswestry Disability Index score (p = 0.03), a lower Short Form 8 Health Survey (SF-8) score (p = 0.001), a lower visual analog scale (VAS) lower back pain score (p = 0.03) and VAS leg pain score (p = 0.0008) at the 12-month follow-up were observed in comparison with the preoperative examination. In MRI volumetry, we detected a median postoperative volume reduction of the disk herniation of 57.1% (p = 0.02). CONCLUSIONS: The transforaminal endoscopic sequestrectomy can be safely implemented in a university hospital setting in selected patients with primary and recurrent lumbar disk herniations, and it leads to good clinical and radiologic results. However, learning curve, caseload, and residents' microsurgical training requirements clearly affect the implementation process.

Role of vasopressin V(1a) and V2 receptors for the development of secondary brain damage after traumatic brain injury in mice.

Brain edema is still one of the most deleterious sequels of traumatic brain injury (TBI), and its pathophysiology is not sufficiently understood. The goal of the current study was to investigate the role of arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), an important regulator of tissue water homeostasis, for the formation of post-traumatic brain edema, intracranial pressure (ICP), brain damage, and functional deficits following brain trauma. C57/B16 mice (n=112) were subjected to controlled cortical impact (CCI; 8m/s, 1 mm). At 3 min after trauma, animals received 500 ng of the AVP V(1a)-receptor antogonist (deamino-Pen(1), O-Me-Tyr(2), Arg(8)]-Vasopressin) or 500 ng of the AVP V2-receptor antagonist (adamantaneacetyl(1), O-Et-D-Tyr(2),Val(4), Abu(6),Arg(8,9)]-Vasopressin) by intracerebroventricular injection. After trauma, cerebral water content (24 h), ICP (24 h), contusion volume (24 h and 7 days), and functional outcome (1-7 days) were assessed (n=8 per experimental group). Post-traumatic inhibition of AVP V(1A) receptors reduced ICP by 29% (p < 0.05), brain water content by 45% (p < 0.05), and secondary contusion expansion by 37% (p < 0.05), and it significantly improved motor function 6 and 7 days after trauma (p < 0.05). Inhibition of AVP V2 receptors had no significant effect. The current results demonstrate that vasopressin V(1A) receptors are involved in the pathogenesis of brain edema formation and the subsequent development of secondary brain damage after traumatic brain injury. Accordingly, our study suggests that vasopressin V(1A) receptors may represent a novel therapeutic target for the treatment of post-traumatic brain edema and secondary brain damage.

Three-dimensional constructive interference in steady-state magnetic resonance imaging in obstructive hydrocephalus: relevance for endoscopic third ventriculostomy and clinical results.

OBJECT: Endoscopic third ventriculostomy is the treatment of choice in patients with obstructive hydrocephalus caused by aqueductal stenosis. The authors examined the clinical course and results of surgical treatment for obstructive hydrocephalus with pre- and postoperative refined constructive interference in steady-state (CISS) MR imaging. METHODS: Forty patients with obstructive hydrocephalus underwent pre- and postoperative 3D-CISS imaging and clinical evaluation. Radiological findings were correlated with intraoperative observations of the thickness and transparency of the floor of the third ventricle and the patient's postoperative clinical course. RESULTS: Three-dimensional CISS MR imaging provides precise visualization of the basilar/posterior cerebral artery, its distance to the clivus, the diameter of the foramen of Monro, and the extension of and thickness of the floor of the third ventricle. In 71% of patients a flow void was detectable postoperatively on the ventriculostomy. In this group 81.5% had strong and 14.8% moderate clinical benefit, and 3.7% required secondary shunt placement. In the remaining 29% of the patients without a visible flow void, strong improvement was seen in 54.5%, moderate improvement in 18.2%, and stoma failure occurred in 27.3% (p = 0.094). Radiological measurements of the thickness of the third ventricle floor correlated with intraoperative findings (r = 0.35, p = 0.029). Comparison of outcomes showed a statistically significant tendency for a better outcome in patients with thin and easily perforated third ventricle floors (p = 0.04). CONCLUSIONS: Endoscopic ventriculostomy in patients with obstructive hydrocephalus is safe and mostly successful, and 3D-CISS MR imaging seems to be a valuable diagnostic method for precisely identifying the anatomy of relevant structures. Furthermore, 3D-CISS MR imaging allows judgment of the thickness of the third ventricle floor and display of the ventriculostomy/flow void, which are predictive for intraoperative course and clinical outcome.

Cerebral Alterations Following Experimental Multiple Trauma and Hemorrhagic Shock.

Multiple trauma (MT) associated with hemorrhagic shock (HS) might lead to cerebral hypoperfusion and brain damage. We investigated cerebral alterations using a new porcine MT/HS model without traumatic brain injury (TBI) and assessed the neuroprotective properties of mild therapeutic hypothermia. Male pigs underwent standardized MT with HS (45% or 50% loss of blood volume) and resuscitation after 90/120 min (T90/T120). In additional groups (TH90/TH120) mild hypothermia (33°C) was induced following resuscitation. Normothermic or hypothermic sham animals served as controls. Intracranial pressure, cerebral perfusion pressure (CPP), and cerebral oxygenation (PtiO2) were recorded up to 48.5 h. Serum protein S-100B and neuron-specific enolase (NSE) were measured by ELISA. Cerebral inflammation was quantified on hematoxylin and eosin -stained brain slices; Iba1, S100, and inducible nitric oxide synthase (iNOS) expression was assessed using immunohistochemistry. Directly after MT/HS, CPP and PtiO2 were significantly lower in T90/T120 groups compared with sham. After resuscitation both parameters showed a gradual recovery. Serum protein S-100B and NSE increased temporarily as a result of MT/HS in T90 and T90/T120 groups, respectively. Cerebral inflammation was found in all groups. Iba1-staining showed significant microgliosis in T90 and T120 animals. iNOS-staining indicated a M1 polarization. Mild hypothermia reduced cerebral inflammation in the TH90 group, but resulted in increased iNOS activation. In this porcine long-term model, we did not find evidence of gross cerebral damage when resuscitation was initiated within 120 min after MT/HS without TBI. However, trauma-related microglia activation and M1 microglia polarization might be a consequence of temporary hypoxia/ischemia and further research is warranted to detail underlying mechanisms. Interestingly, mild hypothermia did not exhibit neuroprotective properties when initiated in a delayed fashion.

Neurosurgery in East Africa: Foundations.

This article is the first in a series of 3 articles that seek to provide readers with an understanding of the development of neurosurgery in East Africa (Foundations), the challenges that arise in providing neurosurgical care in developing countries (Challenges), and an overview of traditional and novel approaches to overcoming these challenges to improve healthcare in the region (Innovations). We review the history and evolution of neurosurgery as a clinical specialty in East Africa. We also review Kenya, Uganda, and Tanzania in some detail and highlight contributions of individuals and local and regional organizations that helped to develop and shape neurosurgical care in East Africa. Neurosurgery has developed steadily as advanced techniques have been adopted by local surgeons who trained abroad, and foreign surgeons who have dedicated part of their careers in local hospitals. New medical schools and surgical training programs have been established through regional and international partnerships, and the era of regional specialty surgical training has just begun. As more surgical specialists complete training, a comprehensive estimation of disease burden facing the neurosurgical field is important. We present an overview with specific reference to neurotrauma and neural tube defects, both of which are of epidemiologic importance as they gain not only greater recognition, but increased diagnoses and demands for treatment. Neurosurgery in East Africa is poised to blossom as it seeks to address the growing needs of a growing subspecialty.

The Growth of Neurosurgery in East Africa: Challenges.

As the second of 3 articles in this series, the aim of this article is to provide readers with an understanding of the development of neurosurgery in East Africa (foundations), the challenges that arise in providing neurosurgical care in developing countries (challenges), and an overview of traditional and novel approaches to overcoming these challenges and improving health care in the region (innovations). Recognizing the challenges that need to be addressed is the first step to implementing efficient and qualified surgery delivery systems in low- and middle-income countries. We reviewed the major challenges facing health care in East Africa and grouped them into 5 categories: 1) burden of surgical disease and workforce crisis; 2) global health view of surgery as "the neglected stepchild"; 3) need for recognizing the surgical system as an interdependent network and importance of organizational and equipment deficits; 4) lack of education in the community, failure of primary care systems, and net result of overwhelming tertiary care systems; 5) personal and professional burnout as well as brain drain of promising human resources from low- and middle-income countries in East Africa and similar regions across the world. Each major challenge was detailed and analyzed by authors who have worked or are currently working in the region, providing a personal perspective.

Neurosurgery in East Africa: Innovations.

In the last 10 years, considerable work has been done to promote and improve neurosurgical care in East Africa with the development of national training programs, expansion of hospitals and creation of new institutions, and the foundation of epidemiologic and cost-effectiveness research. Many of the results have been accomplished through collaboration with partners from abroad. This article is the third in a series of articles that seek to provide readers with an understanding of the development of neurosurgery in East Africa (Foundations), the challenges that arise in providing neurosurgical care in developing countries (Challenges), and an overview of traditional and novel approaches to overcoming these challenges to improve healthcare in the region (Innovations). In this article, we describe the ongoing programs active in East Africa and their current priorities, and we outline lessons learned and what is required to create self-sustained neurosurgical service.

Characterization of microvascular basal lamina damage and blood-brain barrier dysfunction following subarachnoid hemorrhage in rats.

Vasogenic brain edema is one of the major determinants for mortality following subarachnoid hemorrhage (SAH). Although the formation of vasogenic brain edema occurs on the microvascular level by opening of endothelial tight junctions and disruption of the basal lamina, microvascular changes following experimental SAH are poorly characterized. The aim of the present study was therefore to investigate the time course of blood-brain barrier (BBB) dysfunction and basal lamina damage following SAH as a basis for the better understanding of the pathophysiology of SAH. SAH was induced in Sprague-Dawley rats by an endovascular filament. Animals were sacrificed 6, 24, 48, and 72 h thereafter (n=9 per group). Microvascular basal lamina damage was quantified by collagen type IV immunostaining. Western blotting was used to quantify collagen IV protein content and bovine serum albumin (BSA) extravasation as a measure for basal lamina damage and blood-brain barrier disruption, respectively. BSA Western blot revealed significant (p<0.05) BBB opening in the cerebral cortex ipsilateral to the hemorrhage beginning 6 h and peaking 48 h after SAH. Significant (p<0.05) basal lamina damage occurred with gradual increase from 24 to 72 h. Basal lamina damage correlated significantly with BBB dysfunction (r=-0.63; p=0.0001). Microvascular damage as documented by collagen IV degradation and albumin extravasation is a long lasting and ongoing process following SAH. Due to its delayed manner microvascular damage may be prone for therapeutic interventions. However, further investigations are needed to determine the molecular mechanisms responsible for basal lamina degradation and hence damage of the microvasculature following SAH.

Application of a Compact High-Definition Exoscope for Illumination and Magnification in High-Precision Surgical Procedures.

BACKGROUND: The basic necessities for surgical procedures are illumination, exposure, and magnification. These have undergone transformation in par with technology. One of the recent developments is the compact magnifying exoscope system. In this report, we describe the application of this system for surgical operations and discuss its advantages and pitfalls. METHODS: We used the ViTOM exoscope mounted on the mechanical holding arm. The following surgical procedures were conducted: lumbar and cervical spinal canal decompression (n = 5); laminotomy and removal of lumbar migrated disk herniations (n = 4); anterior cervical diskectomy and fusion (n = 1); removal of intraneural schwannomas (n = 2); removal of an acute cerebellar hemorrhage (n = 1); removal of a parafalcine atypical cerebral hematoma caused by a dural arteriovenous fistula (n = 1); and microsutures and anastomoses of a nerve (n = 1), an artery (n = 1), and veins (n = 2). RESULTS: The exoscope offered excellent, magnified, and brilliantly illuminated high-definition images of the surgical field. All surgical operations were successfully completed. The main disadvantage was the adjustment and refocusing using the mechanical holding arm. The time required for the surgical operation under the exoscope was slightly longer than the times required for a similar procedure performed using an operating microscope. CONCLUSIONS: The magnifying exoscope is an effective and nonbulky tool for surgical procedures. In visualization around the corners, the exoscope has better potential than a microscope. With technical and technologic modifications, the exoscope might become the next generation in illumination, visualization, exposure, and magnification for high-precision surgical procedures.