Cerebrospinal Fluid Leakage and Cerebral Venous Sinus Thrombosis: A Case Report

Cerebrovascular venous thrombosis is an uncommon entity that may occur in the sinuses of the dura, the cortical veins, or the deep venous system. Common etiologies include states of hypercoagulability, such as oral contraceptives intake, malignancy, and trauma. Additional causes include inherent thrombophilic states, such as those caused by systemic lupus erythematosus, protein C or S deficiency, and antithrombin III deficiency. The pathogenesis of cerebral venous sinus thrombosis stems from the obstruction of venous outflow. Consequently, venous engorgement occurs, leading to decreased effective blood flow and white matter edema. Infarction or hemorrhage are not uncommon in the setting of venous thrombosis. Intracranial pressure also rises. The most common presenting symptom is headache.2,3 The impact of intracranial hypotension due to cerebrospinal fluid (CSF) leak on venous flow and thrombosis is not clear.1, 4-8, 10, 11 We present the case and treatment course of a patient who initially presented with an acute venous sinus thrombosis and in was later found to have a CSF leak and intracranial hypotension

Moyamoya: A Review of the Disease and Current Treatments

INTRODUCTION Moyamoya disease is a rare progressive cerebrovascular disease characterized by bilateral stenosis of vasculature of the Circle of Willis, specifically the distal internal carotid arteries, that leads to extensive collateral circulation. These dilated collateral vessels are described as having a hazy “puff of smoke” appearance on angiography. “Moyamoya” is the Japanese word for this characteristic appearance. The disease was originally described in Japan in 1957 1 and introduced to the English literature in 1969.2 The disease is most known for its distribution in Asian populations, but recently there has been more research and attention given to moyamoya in Europe and North American Moyamoya disease presents clinically due to the ischemic and hemorrhagic complications of abnormal cerebral vascularity.3,4 Epidemiology Moyamoya disease was originally described in Japanese populations but is present in a variety of ethnicities.3,5,6 In Japan, the incidence per 100,000 patient years is between 0.35 to 0.943 with a male: female ratio of 1:1.87. In the US, incidence ranged from 0.05 to 0.17 per 100,000 patient years with a similar gender distribution.3,6 Other population studies have not been as robust but European studies show moyamoya statistics that are more similar to American findings than those of Asian moyamoya findings.4 There is a bimodal distribution of incidence: in early childhood and adulthood, but the doublepeaked incidence is less dramatic in the US and Europe.4,8 Children typically present with the ischemic symptoms and adults can present with either ischemic or hemorrhagic type, with the ischemic type predominating.5,9 Overall, the hemorrhagic type is more common in Asia than the U.S.9 The incidence has been increasing with time, which may be due to increased awareness.

Comparison of Outcomes in Level I vs Level II Trauma Centers in Patients Undergoing Craniotomy or Craniectomy for Severe Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) carries a devastatingly high rate of morbidity and mortality. OBJECTIVE: To assess whether patients undergoing craniotomy/craniectomy for severe TBI fare better at level I than level II trauma centers in a mature trauma system. METHODS: The data were extracted from the Pennsylvania Trauma Outcome Study database. Inclusion criteria were patients \u3e 18 yr with severe TBI (Glasgow Coma Scale [GCS] score less than 9) undergoing craniotomy or craniectomy in the state of Pennsylvania from January 1, 2002 through September 30, 2017. RESULTS: Of 3980 patients, 2568 (64.5%) were treated at level I trauma centers and 1412 (35.5%) at level II centers. Baseline characteristics were similar between the 2 groups except for significantly worse GCS scores at admission in level I centers (P = .002). The rate of in-hospital mortality was 37.6% in level I centers vs 40.4% in level II centers (P = .08). Mean Functional Independence Measure (FIM) scores at discharge were significantly higher in level I (10.9 ± 5.5) than level II centers (9.8 ± 5.3; P \u3c .005). In multivariate analysis, treatment at level II trauma centers was significantly associated with in-hospital mortality (odds ratio, 1.2; 95% confidence interval, 1.03-1.37; P = .01) and worse FIM scores (odds ratio, 1.4; 95% confidence interval, 1.1-1.7; P = .001). Mean hospital and ICU length of stay were significantly longer in level I centers (P \u3c .005). CONCLUSION: This study showed superior functional outcomes and lower mortality rates in patients undergoing a neurosurgical procedure for severe TBI in level I trauma centers

The ARUBA Trial: How Should We Manage Brain AVMs?

BACKGROUND Brain arteriovenous malformations (bAVMs) are abnormal shunts that bypass the capillary bed and directly divert blood from the arterial to the venous circulation, without exchanging nutrients or dissipating the arterial blood pressure. They are thought to be congenital vascular lesions that occur during the late stages of fetal development, however the exact pathogenesis has not been elucidated yet.1 History of hemorrhage, small AVM size, high arterial feeding blood pressure, and deep venous drainage are the main risk factors that increase the likelihood of AVM rupture. According to the American Stroke Association, 1 in 200-500 people have an AVM, while 25% of AVM patients experience seizures and 50% of patients suffer intracranial hemorrhage (ICH) at some point in their lives.2 Also, 5-15% of AVM patients experience severe headaches because of the increased intracranial pressure and a similar percentage of patients exhibit neurological deficits.1 With the advent of noninvasive imaging, AVMs are being detected at an early, unruptured stage, but the optimal course of action for preventing future complications still remains uncertain. The ARUBA trial strove to determine whether medical management or interventional therapy has a better long-term outcome for patients with unruptured AVMs. While it provides important data, limitations in its study design raise doubts concerning the generalizability of its findings. The study planned to include 800 patients who were to be followed for a minimum of five and a maximum of seven years.3 They were randomly assigned to one of two groups, the interventional therapy and medical management group. Patients in the medical management group received only pharmacological therapy for the medical symptoms that they experienced (unless they developed hemorrhage or infarction, in which case they were switched into the other group). Patients in the interventional therapy group received endovascular surgery, microsurgery, or radiosurgery, with or without pharmacological therapy depending on their concurrent medical conditions. The primary hypothesis was that medical management is more effective in the treatment of patients with unruptured bAVMs, the primary endpoint was death or stroke, the secondary endpoint was the quality of life, while the functional outcome status was measured using the Rankin scale.3 Previous studies had shown that early interventional treatment in patients with ruptured bAVMs is necessary and patients did not have major future clinical problems.3 Interventional therapy includes endovascular surgery, which aims to occlude the nidus by delivering liquid embolics or embolic coils via a catheter, microsurgical resection of the AVM, or radiosurgery that induces a vascular injury response resulting in AVM obliteration within 1 or 2 years.1 A multimodal therapy that involves more than one of these interventional procedures can also be performed on certain patients. Furthermore, medical management was shown to be very effective in treating unruptured bAVMs as indicated by the very low rate of future hemorrhage. Yet, based on data from the Columbia University Medical Center, interventional treatment of ruptured AVMs had a significantly greater likelihood of hemorrhage and/or clinical impairment (Rankin score ≥2) than medical management of unruptured AVMs. It is thus imperative to compare the effectiveness of the two methods of treatment only on patients with unruptured bAVMs, since patients who present with an ICH have an already much higher risk of experiencing a subsequent ICH (hazard ratio of 3.6).4 The ARUBA trial is the first study comparing medical management to surgical care on patients with unruptured bAVMs and a Rankin score less than two.

Comparison of neurologic and radiographic outcomes with Solitaire versus Merci/Penumbra systems for acute stroke intervention.

BACKGROUND AND PURPOSE: The Solitaire Flow Restoration was approved by the FDA in 2012 for mechanical thrombolysis of proximal occlusion of intracranial arteries. To compare the Solitaire FR device and the Merci/Penumbra (previously FDA approved) systems in terms of safety, clinical outcomes, and efficacy including radiographic brain parenchymal salvage. METHODS: Thirty-one consecutive patients treated with the Solitaire and 20 patients with comparable baseline characteristics treated with Merci or Penumbra systems were included in the study. Primary outcome measures included recanalization rate and modified Rankin Scale score at followup. Secondary outcomes included length of procedure, incidence of symptomatic intracranial hemorrhage, 90-day mortality, and radiographic analysis of percentage area salvage. RESULTS: Compared with the Merci/Penumbra group, the Solitaire group showed a statistically significant improvement in favorable outcomes (mRS ≤ 2) (69% versus 35%, P = 0.03) and symptomatic ICH rate (0 versus 15%, P = 0.05) with a trend towards higher recanalization rates (93.5% versus 75%, P = 0.096) and shorter length of procedure (58.5 min versus 70.8 min, P = 0.08). Radiographic comparison also showed a significantly larger area of salvage in the Solitaire group (81.9% versus 71.9%, P = 0.05). CONCLUSION: Our study suggests that the Solitaire system allows faster, safer, and more efficient thrombectomy than Merci or Penumbra systems

Sphenopalatine ganglion stimulation upregulates transport of temozolomide across the blood-brain barrier

Sphenopalatine ganglion (SPG) stimulation has been shown to reversibly alter blood-brainbarrier (BBB) permeability. It is widely used for the treatment of cluster headaches in Europe and iswell tolerated in humans. The therapeutic potential for SPG stimulation in other central nervoussystem (CNS) diseases has yet to be explored. Glioblastoma Multiforme (GBM) remains one of themost difficult primary CNS neoplasms to treat, with an average survival of approximately 18 months atthe time of diagnosis. Since 2004, the gold standard of treatment for GBM in the United States includessurgery followed by treatment with temozolomide (TMZ) and radiation. We sought to determine ifSPG stimulation could increase chemotherapy concentrations in rodent brains with an intact BBB.Here, we show a statistically significant (p=0.0006), five-fold upregulation of TMZ crossing the BBBand reaching brain parenchyma in rats receiving low-frequency (LF, 10 Hz) SPG stimulation. All themeasurements were performed using a highly sensitive liquid chromatography mass spectrometry(LCMS) method that was developed for quantitation of TMZ in plasma and brain tissue. Our treatmentparadigm shows novel delivery route by which we could more effectively and safely deliver TMZ ina targeted manner, to minimize systemic toxicity and maximize action at the target tissue

Microsurgery for cerebral arteriovenous malformations: postoperative outcomes and predictors of complications in 264 cases

Object The authors conducted a study to assess the safety and efficacy of microsurgical resection of arteriovenous malformations (AVMs) and determine predictors of complications. Methods A total of 264 patients with cerebral AVMs were treated with microsurgical resection between 1994 and 2010 at the Jefferson Hospital for Neuroscience. A review of patient data was performed, including initial hemorrhage, clinical presentation, Spetzler-Martin (SM) grade, treatment modalities, clinical outcomes, and obliteration rates. Univariate and multivariate analyses were used to determine predictors of operative complications. Results Of the 264 patients treated with microsurgery, 120 (45%) patients initially presented with hemorrhage. There were 27 SM Grade I lesions (10.2%), 101 Grade II lesions (38.3%), 96 Grade III lesions (36.4%), 31 Grade IV lesions (11.7%), and 9 Grade V lesions (3.4%). Among these patients, 102 (38.6%) had undergone prior endovascular embolization. In all patients, resection resulted in complete obliteration of the AVM. Complications occurred in 19 (7.2%) patients and resulted in permanent neurological deficits in 5 (1.9%). In multivariate analysis, predictors of complications were increasing AVM size (OR 3.2, 95% CI 1.5–6.6; p = 0.001), increasing number of embolizations (OR 1.6, 95% CI 1.1–2.2; p = 0.01), and unruptured AVMs (OR 2.7, 95% CI 1–7.2; p = 0.05). Conclusions Microsurgical resection of AVMs is highly efficient and can be undertaken with low rates of morbidity at high-volume neurovascular centers. Unruptured and larger AVMs were associated with higher complication rates

Endovascular Management of Acute Proximal Internal Carotid Artery Occlusion: the JHN Experience

Stroke is a major cause of serious, long-term disability and the third leading cause of death, accounting for one in every 18 deaths in the United States. Approximately 800,000 strokes occur in the United States each year, leading to an estimated cost of 74 billion dollars in 2010. The severity and prognosis of patients with an acute internal carotid artery (ICA) occlusion is extremely poor. Studies have shown that 16-55% of patients will die from complications related to the infarction, 40-69% will be left with a profound deficit, and only 2-12% will make a reasonable recovery2. In young patients, internal carotid artery dissections presenting as an acute occlusion or thrombotic clot are responsible for approximately 14-20% of ischemic strokes.1 Results from trials utilizing emergent open surgical carotid recanalization or IVtPA have not been encouraging2,3. Recently, there have been small case reports of endovascular stent-assisted thrombolysis as a treatment option for patients with carotid occlusions and near occlusions.4-

Potential Role of Granulocyte–Monocyte Colony-Stimulating Factor in the Progression of Intracranial Aneurysms

Macrophages play a central role in the inflammatory response leading to aneurysm formation, progression, and rupture. The purpose of this study was to determine whether granulocyte–monocyte colony-stimulating factor (GM-CSF) plays a role in the progression of human intracranial aneurysms. Specifically, we investigated whether there was a correlation between the aneurysm size and the concentration of GM-CSF in the lumen of intracranial aneurysms. The concentrations of GM-CSF in blood samples drawn from the lumen of 15 human unruptured saccular intracranial aneurysms of 14 consecutive patients were compared. The aneurysm size was 10.3±9 mm on average. The mean plasma concentration of GM-CSF was 27.9±3.1 pg/mL in the lumen of intracranial aneurysms. The mean plasma concentration of GM-CSF was significantly higher in aneurysms larger than 7 mm (30.1±2.8 pg/mL) compared with aneurysms smaller than 7 mm (26.4±2.4 pg/mL; p=0.02). There was a significant positive correlation between the aneurysm size and the plasma concentration of GM-CSF (Spearman's rho=0.55; p=0.04). There is a significant positive correlation between the aneurysm size and the plasma concentration of GM-CSF in aneurysm lumens. This suggests that GM-CSF, through its stimulatory function on macrophages, may promote aneurysm progression and may be a possible therapeutic target