Fluid dynamics in aging-related dementias.

Recent human and animal model experimental studies revealed novel pathways for fluid movement, immune cell trafficking and metabolic waste clearance in CNS. These studies raise the intriguing possibility that the newly discovered pathways, including the glymphatic system, lymphatic meningeal vessels and skull-brain communication channels, are impaired in aging and neurovascular and neurodegenerative diseases associated with dementia, including Alzheimer's disease (AD) and AD-related dementia. We provide an overview of the glymphatic and dural meningeal lymphatic systems, review current methods and approaches used to study glymphatic flow in humans and animals, and discuss current evidence and controversies related to its role in CNS flow homeostasis under physiological and pathophysiological conditions. Non-invasive imaging approaches are needed to fully understand the mechanisms and pathways driving fluid movement in CNS and their roles across lifespan including healthy aging and aging-related dementia.

Pituitary society expert Delphi consensus: operative workflow in endoscopic transsphenoidal pituitary adenoma resection.

PURPOSE: Surgical workflow analysis seeks to systematically break down operations into hierarchal components. It facilitates education, training, and understanding of surgical variations. There are known educational demands and variations in surgical practice in endoscopic transsphenoidal approaches to pituitary adenomas. Through an iterative consensus process, we generated a surgical workflow reflective of contemporary surgical practice. METHODS: A mixed-methods consensus process composed of a literature review and iterative Delphi surveys was carried out within the Pituitary Society. Each round of the survey was repeated until data saturation and > 90% consensus was reached. RESULTS: There was a 100% response rate and no attrition across both Delphi rounds. Eighteen international expert panel members participated. An extensive workflow of 4 phases (nasal, sphenoid, sellar and closure) and 40 steps, with associated technical errors and adverse events, were agreed upon by 100% of panel members across rounds. Both core and case-specific or surgeon-specific variations in operative steps were captured. CONCLUSIONS: Through an international expert panel consensus, a workflow for the performance of endoscopic transsphenoidal pituitary adenoma resection has been generated. This workflow captures a wide range of contemporary operative practice. The agreed "core" steps will serve as a foundation for education, training, assessment and technological development (e.g. models and simulators). The "optional" steps highlight areas of heterogeneity of practice that will benefit from further research (e.g. methods of skull base repair). Further adjustments could be made to increase applicability around the world.

Cystic appearance on magnetic resonance imaging in bihormonal growth hormone and prolactin tumors in acromegaly.

PURPOSE: To investigate demographic, imaging and laboratory characteristics, and treatment outcomes of acromegaly patients who have bihormonal (BA) growth hormone (GH) and prolactin (PRL) immunoreactive adenomas compared to patients who have densely granulated GH adenomas (DGA) and sparsely granulated GH adenomas (SGA). METHODS: Retrospective review of single-center surgically treated acromegaly patients; pathology was analyzed by a single neuropathologist using 2017 WHO criteria. Preoperative magnetic resonance imaging was assessed to evaluate tumor size, cystic component, invasion and T2 signal intensity. RESULTS: Seventy-seven patients; 19 BA (9 mammosomatotroph and 10 mixed GH and PRL adenomas) were compared with 30 DGA, and 28 SGA. Patients with BA were older than SGA (49.6 vs 38.5 years, p = 0.035), had a higher IGF-1 index (3.3 vs 2.3, p = 0.040) and tumors were less frequently invasive (15.8% vs 57.1%, p = 0.005). BA more frequently had a cystic component on MRI than both SGA and DGA (52.6% vs 14.3%, and 22%, p = 0.005 and 0.033, respectively). When all histological types were combined, biochemical remission postoperatively was more common in non-cystic than cystic tumors (50% vs 22.5%, p = 0.042). Somatostatin receptor ligand response rate was 66.7%, 90.9% and 37.5% in BA, DGA and SGA patients, respectively (p = 0.053). CONCLUSION: Imaging characteristics are an increasingly important adenoma behavior determinant. An adenoma cystic component may suggest that a GH adenoma is a BA. Cystic tumors exhibited lower rates of surgical remission in this series; therefore, optimized individual patient treatment is needed, as patients could be candidates for primary medical treatment.

Pituitary society guidance: pituitary disease management and patient care recommendations during the COVID-19 pandemic-an international perspective.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the viral strain that has caused the coronavirus disease 2019 (COVID-19) pandemic, has presented healthcare systems around the world with an unprecedented challenge. In locations with significant rates of viral transmission, social distancing measures and enforced 'lockdowns' are the new 'norm' as governments try to prevent healthcare services from being overwhelmed. However, with these measures have come important challenges for the delivery of existing services for other diseases and conditions. The clinical care of patients with pituitary disorders typically involves a multidisciplinary team, working in concert to deliver timely, often complex, disease investigation and management, including pituitary surgery. COVID-19 has brought about major disruption to such services, limiting access to care and opportunities for testing (both laboratory and radiological), and dramatically reducing the ability to safely undertake transsphenoidal surgery. In the absence of clinical trials to guide management of patients with pituitary disease during the COVID-19 pandemic, herein the Professional Education Committee of the Pituitary Society proposes guidance for continued safe management and care of this population.

Subarachnoid Hemorrhage Pattern Predicts Acute Cerebral Blood Flow Response in the Rat.

There is considerable variability in the presentation of patients with acute subarachnoid hemorrhage (aSAH). Evidence suggests that a thick, diffuse clot better predicts the development of delayed cerebral ischemia and poor outcomes. In a rodent model of acute SAH, we directly measured the effects of the volume of blood injected versus the pattern of distribution of hemorrhage in the subarachnoid space on markers of early brain injury, namely, cerebral blood flow (CBF), cerebrospinal fluid (CSF) concentrations of P450 eicosanoids and catecholamines, and cortical spreading depolarizations (CSDs). There is a significant decrease in CBF, an increase in CSF biomarkers, and a trend toward increasing frequency and severity of CSDs when grouped by severity of hemorrhage but not by volume of blood injected. In severe hemorrhage grade animals, there was a progressive decrease in CBF after successive CSD events. These results suggest that the pattern of SAH (thick diffuse clots) correlates with the "clinical" severity of SAH.

Silent somatotroph pituitary adenomas: an update.

Silent growth hormone adenomas (SGHA) are a rare entity of non-functioning pituitary neuroendocrine tumors. Diagnosis is invariably made post-operatively of a tumor immunopositive for GH (and Pit-1 in selected cases) but without clinical acromegaly. Mainly young females are affected, and tumors are often uncovered by investigation for headaches or oligoamenorrhea. Integration of clinical, pathological and biochemical data is required for proper diagnosis. Beside normal IGF-1 levels, a third of SGHAs displays elevated GH levels and some will eventually progress to acromegaly. Almost two-thirds will be mixed GH-prolactin tumors and sparsely-granulated monohormonal GH tumors seems the more aggressive subtype. Recurrence and need for radiation is higher than other non-functioning tumors so close follow-up is warranted.

Clinical outcomes in male patients with lactotroph adenomas who required pituitary surgery: a retrospective single center study.

PURPOSE: Lactotroph adenomas (LA) are the most frequently encountered pituitary tumors. Although more frequently observed in women, LAs in men were recently included in a more aggressive category regardless of histological grading, by the WHO. We aimed to perform a rigorous retrospective review of a single center's pre-operative evaluation, patient characteristics and outcomes of male LAs patients requiring pituitary surgery. METHODS: A retrospective review, over 11 years, of patients who underwent resection of a pituitary adenoma at a single center was conducted. Predictors of persistent disease in male LAs patients along with a comparison to predictors of silent corticotroph adenomas (SCAs) patients who also underwent surgery at the center was also conducted. RESULTS: Thirty-one male patients with LAs were identified. When compared to SCAs patients, LAs male patients were younger (41 vs. 50 years of age, p = 0.01). Men with LAs had more invasive tumors (75% vs. 44.7% p = 0.02). More LAs in men had residual tumor after surgery than patients with SCA (92.6% vs. 42.1%, p < 0.001). Male patients with LAs and patients with SCA had similar rates of requiring additional surgery (28.9% vs. 24.1%, p = NS) and radiation therapy (18.4% vs. 19.4%, p = NS). CONCLUSIONS: High rates of DA resistance, invasive tumors and postoperative residual disease in male patients with LA who required surgery are shown. Surgery improved optic chiasm compression, PRL level and central hypogonadism but, not surprisingly, failed to normalize other pituitary hormones and/or eliminate need for DA therapy.

Minimally invasive endoscopic repair of refractory lateral skull base cerebrospinal fluid rhinorrhea: case report and review of the literature.

Cerebrospinal fluid (CSF) leaks occur in approximately 10% of patients undergoing a translabyrinthine, retrosigmoid, or middle fossa approach for vestibular schwannoma resection. Cerebrospinal fluid rhinorrhea also results from trauma, neoplasms, and congenital defects. A high degree of difficulty in repair sometimes requires repetitive microsurgical revisions-a rate of 10% of cases is often cited. This can not only lead to morbidity but is also costly and burdensome to the health care system. In this case-based theoretical analysis, the authors summarize the literature regarding endoscopic endonasal techniques to obliterate the eustachian tube (ET) as well as compare endoscopic endonasal versus open approaches for repair. Given the results of their analysis, they recommend endoscopic endonasal ET obliteration (EEETO) as a first- or second-line technique for the repair of CSF rhinorrhea from a lateral skull base source refractory to spontaneous healing and CSF diversion. They present a case in which EEETO resolved refractory CSF rhinorrhea over a 10-month follow-up after CSF diversions, wound reexploration, revised packing of the ET via a lateral microscopic translabyrinthine approach, and the use of a vascularized flap had failed. They further summarize the literature regarding studies that describe various iterations of EEETO. By its minimally invasive nature, EEETO imposes less morbidity as well as less risk to the patient. It can be readily implemented into algorithms once CSF diversion (for example, lumbar drain) has failed, prior to considering open surgery for repair. Additional studies are warranted to further demonstrate the outcome and cost-saving benefits of EEETO as the data until now have been largely empirical yet very hopeful. The summaries and technical notes described in this paper may serve as a resource for those skull base teams faced with similar challenging and otherwise refractory CSF leaks from a lateral skull base source.

Current and potential imaging applications of ferumoxytol for magnetic resonance imaging.

Contrast-enhanced magnetic resonance imaging is a commonly used diagnostic tool. Compared with standard gadolinium-based contrast agents, ferumoxytol (Feraheme, AMAG Pharmaceuticals, Waltham, MA), used as an alternative contrast medium, is feasible in patients with impaired renal function. Other attractive imaging features of i.v. ferumoxytol include a prolonged blood pool phase and delayed intracellular uptake. With its unique pharmacologic, metabolic, and imaging properties, ferumoxytol may play a crucial role in future magnetic resonance imaging of the central nervous system, various organs outside the central nervous system, and the cardiovascular system. Preclinical and clinical studies have demonstrated the overall safety and effectiveness of this novel contrast agent, with rarely occurring anaphylactoid reactions. The purpose of this review is to describe the general and organ-specific properties of ferumoxytol, as well as the advantages and potential pitfalls associated with its use in magnetic resonance imaging. To more fully demonstrate the applications of ferumoxytol throughout the body, an imaging atlas was created and is available online as supplementary material.

Hibernation, Hypothermia and a Possible Therapeutic "Shifted Homeostasis" Induced by Central Activation of A1 Adenosine Receptor (A1AR).

The positive outcome that hypothermia contributes to brain and cardiac protection following ischemia has stimulated research in the development of pharmacological approaches to induce a hypothermic/hypometabolic state. Pharmacological manipulation of central autonomic thermoregulatory circuits could represent a potential target for the induction of a hypothermic state. Here we present a brief description of the CNS thermoregulatory centers and how the manipulation of these circuits can be useful in the treatment of pathological conditions such as stroke or brain hemorrhage.

Soluble Epoxide Hydrolase in Hydrocephalus, Cerebral Edema, and Vascular Inflammation After Subarachnoid Hemorrhage.

BACKGROUND AND PURPOSE: Acute communicating hydrocephalus and cerebral edema are common and serious complications of subarachnoid hemorrhage (SAH), whose causes are poorly understood. Using a mouse model of SAH, we determined whether soluble epoxide hydrolase (sEH) gene deletion protects against SAH-induced hydrocephalus and edema by increasing levels of vasoprotective eicosanoids and suppressing vascular inflammation. METHODS: SAH was induced via endovascular puncture in wild-type and sEH knockout mice. Hydrocephalus and tissue edema were assessed by T2-weighted magnetic resonance imaging. Endothelial activation was assessed in vivo using T2*-weighted magnetic resonance imaging after intravenous administration of iron oxide particles linked to anti-vascular cell adhesion molecule-1 antibody 24 hours after SAH. Behavioral outcome was assessed at 96 hours after SAH with the open field and accelerated rotarod tests. RESULTS: SAH induced an acute sustained communicating hydrocephalus within 6 hours of endovascular puncture in both wild-type and sEH knockout mice. This was followed by tissue edema, which peaked at 24 hours after SAH and was limited to white matter fiber tracts. sEH knockout mice had reduced edema, less vascular cell adhesion molecule-1 uptake, and improved outcome compared with wild-type mice. CONCLUSIONS: Genetic deletion of sEH reduces vascular inflammation and edema and improves outcome after SAH. sEH inhibition may serve as a novel therapy for SAH.

Protective role of p450 epoxyeicosanoids in subarachnoid hemorrhage.

BACKGROUND: Patients recovering from aneurysmal subarachnoid hemorrhage (SAH) are at risk for developing delayed cerebral ischemia (DCI). Experimental and human studies implicate the vasoconstrictor P450 eicosanoid 20-hydroxyeicosatetraenoic acid (20-HETE) in the pathogenesis of DCI. To date, no studies have evaluated the role of vasodilator epoxyeicosatrienoic acids (EETs) in DCI. METHODS: Using mass spectrometry, we measured P450 eicosanoids in cerebrospinal fluid (CSF) from 34 SAH patients from 1 to 14 days after admission. CSF eicosanoid levels were compared in patients who experienced DCI versus those who did not. We then studied the effect of EETs in a model of SAH using mice lacking the enzyme soluble epoxide hydrolase (sEH), which catabolizes EETs into their inactive diol. To assess changes in vessel morphology and cortical perfusion in the mouse brain, we used optical microangiography, a non-invasive coherence-based imaging technique. RESULTS: Along with increases in 20-HETE, we found that CSF levels of 14,15-EET were elevated in SAH patients compared to control CSF, and levels were significantly higher in patients who experienced DCI compared to those who did not. Mice lacking sEH had elevated 14,15-EET and were protected from the delayed decrease in microvascular cortical perfusion after SAH, compared to wild type mice. CONCLUSIONS: Our findings suggest that P450 eicosanoids play an important role in the pathogenesis of DCI. While 20-HETE may contribute to the development of DCI, 14,15-EET may afford protection against DCI. Strategies to enhance 14,15-EET, including sEH inhibition, should be considered as part of a comprehensive approach to prevent DCI.

Response to Preoperative Dexamethasone Predicts Postoperative Neurological Improvement of Focal Neurological Deficits in Patients With Brain Metastases.

BACKGROUND: Steroids are used ubiquitously in the preoperative management of patients with brain tumor. The rate of improvement in focal deficits with steroids and the prognostic value of such a response are not known. OBJECTIVE: To determine the rate at which focal neurological deficits respond to preoperative corticosteroids in patients with brain metastases and whether such an improvement could predict long-term recovery of neurological function after surgery. METHODS: Patients with brain metastases and related deficits in language, visual field, or motor domains who received corticosteroids before surgery were identified. Characteristics between steroid responders and nonresponders were compared. RESULTS: Ninety six patients demonstrated a visual field (13 patients), language (19), or motor (64) deficit and received dexamethasone in the week before surgery (average cumulative dose 43 mg; average duration 2.7 days). 38.5% of patients' deficits improved with steroids before surgery, while 82.3% of patients improved by follow-up. Motor deficits were more likely to improve both preoperatively ( P = .014) and postoperatively ( P = .010). All 37 responders remained improved at follow-up whereas 42 of 59 (71%) of nonresponders ultimately improved ( P < .001). All other clinical characteristics, including dose and duration, were similar between groups. CONCLUSION: A response to steroids before surgery is highly predictive of long-term improvement postoperatively in brain metastasis patients with focal neurological deficits. Lack of a response portends a somewhat less favorable prognosis. Duration and intensity of therapy do not seem to affect the likelihood of response.

Innovative growth and development of a neurological surgery residency cadaveric skull base simulation training program: A single institution experience.

OBJECTIVE: Neurosurgical cadaveric and simulation training is a valuable opportunity for residents and fellows to develop as neurosurgeons, further neuroanatomy knowledge, and develop decision-making and technical expertise. The authors describe the growth and development of Oregon Health & Science University (OHSU) Department of Neurological Surgery (NSG) resident hands-on simulation skull base course and provide details of course layout and setup. METHODS: A three-part surgical simulation series was created to provide training in cadaveric skull base procedures. Course objectives were outlined for participants. Residents participated in NSG hands-on simulation courses (years 2015-2020) and completed annual course curriculum and anonymous course evaluations, which included free text reviews. Courses were evaluated by Likert scale analysis within Python, and free text was quantified using Valence Aware Dictionary for sEntiment Reasoning (VADER). Descriptive statistics were calculated and plotted using Python's Seaborn and Matplotlib library modules. RESULTS: Analysis included 162 skull base (anterior fossa, middle fossa and lateral, and endoscopic endonasal-based) simulation course evaluations. Resident responses were overwhelmingly positive. Likert responses demonstrated high average responses for each question (4.62 ± 0.56 and above). A positive attitude about simulation courses is supported by an average compound sentiment value of 0.558 ± 0.285. CONCLUSION: This is the first time Likert responses and sentiment analysis have been used to demonstrate how neurosurgical residents view a comprehensive, multi-year hands-on simulation training program. We hope the information presented serves as a guide for other institutions to develop their own residency educational curriculum in cadaveric skull base procedures.

Steroid psychosis: a review for neurosurgeons.

Steroids are beneficial in neurological illness, but have many serious side effects. Having observed several patients with severe steroid psychoses, which greatly prolonged their hospitalizations, the authors sought to improve understanding of this entity. A literature review was conducted. The incidence of severe psychiatric symptoms was estimated in a meta-analysis of 2,555 patients to be 5.7 % and the incidence of any psychiatric symptoms was 18.6 % in patients receiving >80 mg/day of prednisone (12 mg/day dexamethasone). Dose is not predictive of time of onset, severity, type, or duration of symptoms. Symptoms can develop rapidly following exposure to even low doses and with oral, epidural, or intra-articular administration. Glucocorticoid effects on the brain fall into three categories: genomic, non-genomic, and neurotrophic/neurotoxic and can be permanent. Excessive glucocorticoid exposure may result in decreased production of endogenous neurosteroid molecules, resulting in unopposed glucocorticoid effects. Treatment includes early recognition, steroid withdrawal when appropriate, reduction in stimulation, and medication. Atypical antipsychotics like olanzapine and risperidone may cause fewer dystonic reactions and extrapyramidal symptoms than typical antipsychotics like haloperidol, and therefore, are often recommended as first line treatment. Steroids are powerful medications with many undesirable side effects. They should be used with caution. More research is needed on their effects on the human central nervous system.

Determinants of survival in sinonasal and skull base chondrosarcoma: An analysis of the National Cancer Database.

BACKGROUND: Chondrosarcomas are rare, malignant chondroid tumors that can occur in the sinonasal and skull base regions. Surgery is a mainstay of treatment, but complete resection can be challenging because of the close proximity of critical neurovascular structures. Because of their rarity and relatively indolent nature, optimal treatment regimens are not established. Our objective was to assess determinants of survival for sinonasal and skull base chondrosarcomas utilizing the National Cancer Database (NCDB). METHODS: The NCDB (2004-2017) was queried for cases of sinonasal and skull base chondrosarcoma. Multivariate hazard regression modeling was used to identify significant predictors of 60-month and 120-month overall survival (OS). RESULTS: Seven hundred thirty-six cases met inclusion criteria. OS for all treatment types was 84.7% [SE±0.02] at 60 months and 75.6% [SE±0.02] at 120 months. Surgery with or without adjuvant treatment was found to associate with highest OS at 60 and 120 months. For patients receiving adjuvant radiation during treatment, proton therapy had significantly better OS at 60 months (95.4% [SE±0.03] vs 82.3% [SE±0.03], -2  = 5.27; p = 0.02) and 120 months (85.1% [SE±0.08] vs 72.8% [SE±0.05], -2  = 4.11; p = 0.04) compared with conventional external beam. After adjustment for primary site, multivariate Cox regression modeling (n = 561) identified cofactors significantly associated with variation in mortality risk at 60 and 120 months, including age, Charlson-Deyo total score ≥ 3, insurance provision status, and tumor grade. CONCLUSIONS: Sinonasal and skull base chondrosarcoma are primarily treated with surgery with favorable OS. Adjuvant treatment may be required and proton radiation was associated with improved 60-month and 120-month survival compared with conventional radiation.

Endoscopic Endonasal Eustachian Tube Obliteration as a Treatment for Tension Pneumocephalus After Translabyrinthine Resection of Vestibular Schwannoma.

OBJECTIVE: Cerebrospinal fluid leak and pneumocephalus are rare but potentially devastating complications associated with translabyrinthine resection of cerebellopontine angle masses. Persistent pneumocephalus despite proximal eustachian tube (ET) obliteration is rare. We describe, to our knowledge, the first report of successful management of tension pneumocephalus by endoscopic endonasal ET obliteration using a novel V-loc (Covidien; Medtronic, Minneapolis, MN) suture technique. PATIENTS: A 63-year-old man presented with altered mental status 10 months after translabyrinthine excision of a left cerebellopontine angle vestibular schwannoma measuring 2.8 × 2.9 × 3.3 cm. Computed tomography demonstrated diffuse ventriculomegaly and new pneumocephalus along the right frontal lobe, lateral ventricles, and third ventricle, and air within the left translabyrinthine resection cavity. INTERVENTION: The patient underwent left-sided endoscopic endonasal ET obliteration using 2-0, 9-inch V-loc suture. MAIN OUTCOME MEASURE: Postoperatively, the patient's mental status improved with a decrease in size of the lateral and third ventricles on computed tomography. CONCLUSION: Endoscopic endonasal ET obliteration, a technique previously applied to recalcitrant cerebrospinal fluid leaks, is a safe and reasonable alternative to reentering the original surgical site for patients with pneumocephalus after lateral skull base surgery. Utilizing a V-loc suture for this technique instead of a traditional suture may improve procedural ease and speed.

A technical note on anterolateral mobilization in vertebrobasilar dolichoectasia for relief of brainstem compression.

Vascular compression of neural tissue causing neurological symptoms is a wellknown phenomenon. This is commonly seen in trigeminal neuralgia and, less commonly, in hemifacial spasm by small arteries, which can be treated by microvascular decompression. Rarely, larger arteries, such as the vertebral arteries, may compress the brainstem. This can lead to symptoms of pontine or medullary distress like hemiparesis, dysphagia, or respiratory distress. This is treated by macrovascular decompression. Due to the rare and heterogenous nature of this disease, there is no standardized approach. We describe a novel technique whereby the vertebrobasilar system is mobilized anterolaterally towards the occipital condyle with a sling to decompress the brainstem.
We report two cases of vertebrobasilar dolichoectasia causing brainstem compression. A carotid patch graft sling with anterolateral mobilization to the occipital condyle is described as a surgical nuance to macrovascular decompressive surgery. Briefly, the vertebral artery was identified and dissected away from the brainstem and the bulbar cranial nerves. Bovine pericardium graft was used to create a sling around the artery by suturing the two ends together. The sling was then fixed either to the occipital condyle using cranial plating screws or suturing to the dura of the occipital condyle.
A novel surgical technique for management of vertebrobasilar dolichoectasia causing brainstem compression with progressive neurological deterioration is reported. Anatomical location and the offending vessel should guide neurosurgeons to select the best surgical option to achieve complete decompression of the involved neural structures.

In a model of SAH-induced neurogenic fever, BAT thermogenesis is mediated by erythrocytes and blocked by agonism of adenosine A1 receptors.

Neurogenic fever (NF) after subarachnoid hemorrhage (SAH) is a major cause of morbidity that is associated with poor outcomes and prolonged stay in the neurointensive care unit (NICU). Though SAH is a much more common cause of fever than sepsis in the NICU, it is often a diagnosis of exclusion, requiring significant effort to rule out an infectious source. NF does not respond to standard anti-pyretic medications such as COX inhibitors, and lack of good medical therapy has led to the introduction of external cooling systems that have their own associated problems. In a rodent model of SAH, we measured the effects of injecting whole blood, blood plasma, or erythrocytes on the sympathetic nerve activity to brown adipose tissue and on febrile thermogenesis. We demonstrate that following SAH the acute activation of brown adipose tissue leading to NF, is not dependent on PGE2, that subarachnoid space injection of whole blood or erythrocytes, but not plasma alone, is sufficient to trigger brown adipose tissue thermogenesis, and that activation of adenosine A1 receptors in the CNS can block the brown adipose tissue thermogenic component contributing to NF after SAH. These findings point to a distinct thermogenic mechanism for generating NF, compared to those due to infectious causes, and will hopefully lead to new therapies.

Cerebrospinal Fluid Hypovolemia: A Case Report of a Red Herring.

Mild intracranial hypotension can lead to classically recognizable symptoms such as positional headaches, nausea, vomiting, and occasionally blurred vision. Less commonly, severe cerebrospinal fluid (CSF) hypovolemia can lead to a life-threatening condition that mimics intracranial hypertension, including transtentorial herniation and subsequent rapid neurologic decline. In this report we present a unique case of severe intracranial hypotension from a thoracic tumor resection that led to symptoms initially mistaken for intracranial hypertension, however ultimately correctly diagnosed as severe CSF hypovolemia that improved with dural repair. Additionally, we describe a rare angiography finding associated with CSF hypovolemia, kinking of the basilar artery. Here we report a 47-year-old female with neurofibromatosis Type 2 found to have a T3 intradural extramedullary tumor. She initially presented with urinary incontinence and gait/balance difficulty. She underwent thoracic laminectomies at T3 and T4 for the excision of the lesion. She was discharged on postoperative day 4. On postoperative day 9, she was noted to have nausea, vomiting, and decreased consciousness. Head computed tomography (CT) demonstrated acute downward herniation. She was transferred to our institution from a community facility obtunded and was intubated for airway protection. She was placed in the Trendelenburg position with immediate improvement, and declined every time her head was raised. Angiogram showed significant kinking of her basilar artery. A CT myelogram revealed a CSF leak from her recent thoracic surgery. She underwent exploration of her thoracic wound, and a ventral durotomy was repaired. Following this, she began to tolerate the head of bed elevations and recovered back to her neurologic baseline. A postoperative head CT angiography obtained before discharge showed improvement of her basilar kink. Mild intracranial hypotension is a common finding in patients who undergo procedures that enter the CSF space. Severe intracranial hypotension can easily be missed diagnosed as the signs on the exam are similar to patients with signs of intracranial hypertension. It is of paramount importance that the clinician recognizes brain sag, as the treatment algorithms are vastly different from that of intracranial hypertension leading to transtentorial herniation.