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Background:  All brain surgery requires some degree of iatrogenic trauma to healthy tissue. Minimally invasive approaches to brain tumors offer the potential of decreasing this trauma compared with conventional approaches. However, there are no validated radiologic models to examine axonal damage after minimally invasive entry into the brain., Objective:  To present a cadaveric model of brain cannulation using fractional anisotropy measurements obtained from diffusion tensor magnetic resonance imaging (MRI). Two different methods of access are compared., Methods:  Freshly harvested unfixed cadaveric brains were cannulated using both direct and indirect (i.e., dilation followed by cannulation) methods. Specimens were subjected to 68-direction diffusion tensor imaging scans and proton-density imaging. Fractional anisotropy (FA) data from a region of interest surrounding the entry zone was extracted from scans using imaging software and analyzed., Results:  FA values were significantly higher following indirect cannulation (less invasive method) than they were following direct cannulation. FA values for undisturbed brain were significantly higher than in either of the cannulated groups, suggesting an inverse relationship between FA values and brain injury., Conclusion:  Axonal damage following brain cannulation can potentially be evaluated by FA analysis in a cadaveric model. These data may lead to an MRI-based model of iatrogenic brain injury following tumor surgery. Future studies will focus on histologic analysis and clinical validation in live tissues., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart · New York.)

Traumatic clival fractures in the pediatric population are associated with high mortality rates. In our previously reported series, a subset of clival fractures were associated with traumatic diastasis of the surrounding clival synchondroses. Herein, we describe a pediatric case of an isolated traumatic diastasis of the clival synchondroses without clival fracture with significant injury to neurovascular structures. To our knowledge this is the first report to describe this entity. Careful radiological attention should be made towards the clival synchondroses in crushing head injuries to best tailor screening for cerebrovascular injury even in the absence of clival fractures., (© 2018 S. Karger AG, Basel.)

Background: Spontaneous intracerebral hemorrhages (ICHs) cause significant morbidity and mortality. Traditional open surgical management strategies offer limited benefit except for the most superficial hemorrhages in select patients. Recent reports suggest that endoscopic approaches may improve outcomes, particularly for deep subcortical hemorrhages. However, the management of these patients remains controversial. We reviewed our experience using endoscopic port surgery to identify characteristics that may predict acceptable outcomes., Materials and Methods: We completed a retrospective chart and imaging review of patients who underwent endoscopic port surgery for evacuation of spontaneous ICH at a single center. Data were gathered regarding patient demographics, hemorrhage locations, operative findings, and clinical outcomes., Results: From 2007 to 2011, 18 patients underwent evacuation of spontaneous intracerebral hematomas using an endoscopic port. The mean age in years was 62 years (range, 43-84 years). Six of 18 patients (33%) died before discharge, and 2 others (11%) died after at least 1 month of survival. Of 12 initial survivors, all were discharged to a rehabilitation or nursing facility. Complete hematoma evacuation was achieved in 7 of 18 patients, with the remaining 11 having a partial evacuation. The patients who died (n = 6) before discharge were statistically more likely to have a left-sided hemorrhage, partial evacuation, or older age than the survivors; death at least 1  month after evacuation was additionally associated with greater preoperative hematoma volumes., Conclusions: Our series demonstrates that endoscopic port surgery for acute intracerebral hematoma evacuation has the ability to achieve significant decompression of large and deep-seated hematomas. Patient age, extent of evacuation, laterality, and preoperative hematoma volume appear to influence patient outcome. Most overall outcomes remain poor. Future studies are necessary to determine if surgical evacuation is in fact superior to best medical treatment and if so, to validate, refute, or further identify characteristics that define surgical candidates., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Mass lesions of the inferior, middle, and superior cerebellar peduncles (cerebellar peduncle complex [CPC]) present numerous surgical pitfalls when resection or debulking is warranted. Success has been achieved through multiple approaches, but complications can be severe., Objective: To report the surgical technique for and clinical results of the treatment of lesions in the CPC with an endoscopic port via a lateral transcerebellar corridor., Methods: Three patients underwent resection of intrinsic lesions of the CPC via a lateral transcerebellar approach with an endoscopic port. Deployment of the port was performed with frameless image-guided placement into the area of interest. Resection was performed using bimanual microsurgical technique under parallel endoscopic visualization., Results: Three patients 43, 27, and 13 years of age underwent successful resection of lesion in the CPC. Histopathological diagnosis consisted of cavernous malformation, glioblastoma multiforme, and a juvenile pilocytic astrocytoma. All had complete gross total resection except for the patient with a high-grade glioma. Clinically, all had excellent outcomes, with 1 patient suffering postoperative facial palsy after resection of her high-grade glioma., Conclusion: The lateral transcerebellar approach to the CPC with an endoscopic port may be a feasible alternative to standard microsurgical resection in such difficult cases. Careful patient selection is critical to identify those who may be suitable for endoscopic port surgery on the basis of clinical, radiographic, and anatomical considerations.

Object: Fractures of the clivus and traumatic diastases of the clival synchondroses are rare in the pediatric population. The incidence, outcome, and biomechanics associated with these fractures have been difficult to ascertain secondary to the lack of literature pertaining to their occurrence., Methods: A Boolean search of the electronic medical record database at the Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, was performed to identify patients with fractures of the clivus that were diagnosed using CT of the head. A retrospective review of the chart and radiographic imaging was then performed to assess data regarding patient demographics, mechanism of injury, and skull and brain parenchymal injuries, as well as outcomes., Results: Between May 2002 and November 2007, 16 patients with fractures of the clivus were identified. The mean age of these patients was 9 years (range 1-16 years). Eleven (68.8%) of the 16 patients had an associated traumatic diastasis of the central skull base. Five (31.3%) of the 16 patients died. However, of the 11 patients who survived, all had a good outcome with a Glasgow Outcome Scale score of 4 or 5 at the time of discharge. The incidence of clival fractures among patients with head injuries was 0.33%., Conclusions: Clival fractures occur with a similar incidence in both the pediatric and adult trauma population. Outcome is not correlated directly with the extent of clival fracture, but rather with the presenting Glasgow Coma Scale score and concomitant brain parenchymal injuries. The identification of traumatic diastases in patients with clival fractures suggests that static loading forces are a significant factor in the biomechanics producing these types of fractures.

Background: Intraventricular lesions are challenging entities that may be difficult to resect completely and safely, especially larger lesions with high vascularity or firm consistency., Objective: To assess the results of stereotactically guided endoscopic port (SEP) surgery for resection of colloid cysts and intraventricular tumors., Methods: The authors developed a minimally invasive microsurgical technique for intraventricular surgery using parallel endoscopy to visualize the lesion. Surgical resection was performed via an 11.5-mm transparent conduit (Neuroendoport) deployed under stereotactic guidance. Forty-seven consecutive cases were performed, and all had a minimum 1-year follow-up to assess the efficacy of the technique., Results: For colloid cysts, gross total resection was achieved in 31 (96.9%) of the 32 cases. The transient neurologic morbidity rate was 9.4%; no permanent neurologic morbidity occurred. For intraventricular tumors, gross or near total resection was achieved in 80% of cases. The transient neurological morbidity rate was 6.7%, and no permanent neurological morbidity occurred., Conclusion: SEP surgery for colloid cysts and intraventricular tumors proved to be a safe and effective alternative to conventional microsurgical resection. This technique was not limited by the vascularity, friability, or size of any of the lesions.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft-tissue neoplasm that most commonly appears in the limbs, typically affecting children and young adults. The tumor has a propensity for local recurrence and recurrent hemorrhage but rarely for remote metastasis. To date, only 2 reports have documented an intracranial occurrence of the tumor (1 of which was believed to be metastatic disease). This is the second report of primary intracranial AFH. Additionally, hemorrhage from an intracranial AFH lesion has yet to be reported, and little is known about the radiographic characteristics and biological behavior of these lesions. In this report, the authors describe the case of a patient with recurrent hemorrhage due to primary multifocal intracranial AFH. Initially misdiagnosed as a cavernous malformation and then an unusual meningioma, the tumor was finally correctly identified when there was a large enough intact resection specimen to reveal the characteristic histological pattern. The diagnosis was confirmed using immunohistochemical and molecular studies.

Evidence suggests that the gamma-aminobutyric acid (GABA)ergic system may be involved in cognitive dysfunction following traumatic brain injury (TBI). We investigated the effect of flumazenil treatment, a benzodiazepine antagonist approved by the U.S. Food and Drug Administration, on learning and memory in the immature rat following experimental brain injury. Post-natal day 17 rats were injured using controlled cortical impact. Systemic treatment with flumazenil at 1, 5, and 10 mg/kg was initiated on post-injury day 1 and administered for 13 days via daily intraperitoneal injections. Morris water maze (MWM) testing was used to measure latency to find a submerged platform and the results from experimental and control animals were compared. We demonstrated a significant dose-dependent improvement in MWM performance in drug-treated animals. This is the first study demonstrating the efficacy of flumazenil in reducing post-TBI cognitive deficits and we propose that these effects may be related to modulation of the GABA(A) receptor.

Objective: We report the morbidity and mortality associated with fractures of the clivus and discuss management approaches specific to this unique diagnostic entity., Methods: We performed a boolean search of our electronic medical record database to identify patients with fractures of the clivus that were diagnosed using computed tomography of the head. A retrospective imaging and chart analysis was completed to further characterize the fractures and to analyze outcomes., Results: Between January 1999 and December 2007, 41 patients were identified with fractures of the clivus. We found a 0.21% overall incidence among all head-injured patients presenting to our institution and a 2.3% incidence among those patients with a cranial fracture. Ten of 41 patients (24.4%) died, and neurological and vascular complications associated with central cranial base fractures were observed in 19 of 41 patients (46%). Furthermore, associated cranial fractures remote from the central cranial base and associated intracranial hemorrhages were observed in 40 of 41 (97.6%) and 33 of 41 (80.5%) patients, respectively. In terms of outcomes, 26 of 41 patients (63.5%) had a Glasgow Coma Scale score of 12 or greater at the time of discharge from the hospital., Conclusion: We demonstrate a lower than previously reported mortality rate in patients with clival fractures. Nevertheless, as a result of location, fractures of the clivus were frequently associated with a high rate of complications and neurological sequelae.

The authors report the safety and efficacy of using a percutaneous minimal-access insertion technique for distal shunt catheter placement in 100 cases. From June 2007 to March 2008, they attempted 100 minimal-access insertions of distal shunt catheters in 91 patients who required ventriculoperitoneal shunting. Using the minimal-access approach, they avoided utilizing laparoscopic assistance or a mini-laparotomy in 91% of the cases. There were no bowel injuries or misplaced distal catheters. Additional outcomes in terms of operative times, cases that required conversion to open or laparoscopically assisted implantation, and infection rates are presented. They conclude that intraperitoneal shunt catheter placement can be safely and effectively accomplished using a simplified percutaneous minimal-access insertion method that does not require direct laparoscopic visualization.

The authors report on a case of successful reversal of sedation with flumazenil, a benzodiazepine antagonist, in a child following a moderate traumatic brain injury and demonstrate the utility of flumazenil to reverse benzodiazepine effects in traumatically injured children.

Palmar hyperhidrosis is a disorder of the autonomic nervous system characterized by excessive perspiration of the palms, but may involve other body parts as well. Traditional posterior approaches have been performed less often in favor of less invasive thoracoscopic sympathectomies, which have a high success rate with low associated morbidity. However, some patients are not candidates for a transthoracic surgery and may need an alternative treatment strategy. In situations in which a posterior approach may be necessary, the authors have developed a minimal access endoscopic-assisted dorsal sympathectomy procedure, applying minimally invasive spine muscle splitting techniques. The authors believe that the development of this technique may help to minimize surgical morbidity associated with the traditional posterior approach by reducing pain, tissue damage, and length of postoperative recovery. This paper is a report on the successful treatment of palmar hyperhidrosis using a minimally invasive posterior technique and describes the surgical approach and outcomes in 2 patients who have been treated in this manner. Two patients underwent minimally invasive endoscopic-assisted posterior thoracic sympathectomy for hyperhidrosis. Both patients experienced relief of their symptoms after surgery with follow-up durations of 32 and 9 months and length of stays of 0.9 and 2.8 days, respectively. One patient suffered a unilateral Horner syndrome and underwent an eyelid lift. The other patient was readmitted to the hospital 2 days after discharge with atelectasis. She was obese and suffered from chronic obstructive pulmonary disease at baseline, which were reasons she opted for a posterior approach. Neither patient suffered a pneumo- or hemothorax. Minimally invasive endoscopic-assisted posterior thoracic sympathectomy can be safely performed for relief of hyperhidrosis. The procedure has risks for the usual complications of sympathectomy. This technique may provide an alternative to thoracoscopic approaches, especially in those patients with pulmonary disease or obesity.

Nucleokinesis has recently been suggested as a critical regulator of neuronal migration. Here we show that Disabled 1 (Dab1), which is required for neuronal positioning in mammals, regulates the nuclear position of postmitotic neurons in a phosphorylation-site dependent manner. Dab1 expression in the Drosophila visual system partially rescues nuclear position defects caused by a mutation in the Dynactin subunit Glued. Furthermore, we observed that a loss-of-function allele of amyloid precursor protein (APP)-like, a kinesin cargo receptor, enhanced the severity of a Dab1 overexpression phenotype characterized by misplaced nuclei in the adult retina. In mammalian neurons, overexpression of APP reduced the ability of Reelin to induce Dab1 tyrosine phosphorylation, suggesting an antagonistic relationship between APP family members and Dab1 function. This is the first evidence that signaling which regulates Dab1 tyrosine phosphorylation determines nuclear positioning through Dab1-mediated influences on microtubule motor proteins in a subset of neurons.

Reelin-induced Dab1 tyrosine phosphorylation has been implicated in the regulation of neuronal positioning during brain development. The downstream consequences of Dab1 tyrosine phosphorylation are not fully understood, however. Here we identify CrkII, CrkL and Dock1 in complexes bound to tyrosine-phosphorylated Dab1, through mass spectrometry. The CrkII-Dab1 interaction requires tyrosine phosphorylation of Dab1 at residues 220 or 232 and is promoted by Reelin treatment of embryonic forebrain neurons. Unlike other CrkII binding proteins, such as paxillin and p130Cas, expression of Dab1 interfered with CrkII-dependent cell migration of Nara Bladder Tumor II (NBT-II) cells, in a tyrosine phosphorylation-site dependent manner. Overexpression of CrkIIGFP rescued the migration of these cells, suggesting that Dab1 makes Crk a limiting factor for migration. The Dock1-Dab1 association is indirect and requires CrkII. In organisms such as Drosophila melanogaster and Caenorhabditis elegans, signaling complexes, which contain Crk and Dock1 family members are conserved and act through Rac. We show that a rough-eye phenotype in Drosophila caused by exogenous expression of tyrosine-phosphorylated mouse Dab1RFP is partially rescued by a loss-of-function mutation in myoblast city, a Dock1-like gene in Drosophila. We propose a model that tyrosine-phosphorylated Dab1 engages the conserved Crk-Dock1-Rac signaling cassette, but when bound to Dab1 this signaling complex does not support migration.

The tyrosine phosphorylation sites of the Disabled 1 (Dab1) docking protein are essential for the transmission of the Reelin signal, which regulates neuronal placement. Here we identify Nck beta as a phosphorylation-dependent, Dab1-interacting protein. The SH2 domain of Nck beta but not Nck alpha binds Dab1 phosphorylated on the Reelin-regulated site, Y220, or on Y232. Nck beta is coexpressed with Dab1 in the developing brain and in cultured neurons, where Reelin stimulation leads to the redistribution of Nck beta from the cell soma into neuronal processes. We found that tyrosine-phosphorylated Dab1 in synergy with Nck beta disrupts the actin cytoskeleton in transfected cells. In Drosophila melanogaster, exogenous expression of mouse Dab1 causes tyrosine phosphorylation site-dependent morphological changes in the compound eye. This phenotype is enhanced by overexpression of the Drosophila Nck protein Dock, suggesting a conserved interaction between the Disabled and Nck family members. We suggest a model in which Dab1 phosphorylation leads to the recruitment of Nck beta to the membrane, where it acts to remodel the actin cytoskeleton.