Multiple intracranial aneurysms in a patient with type I Gaucher disease: a case report and literature review.

Multiple intracranial aneurysms (IAs) have never been reported in a patient with Gaucher disease (GD). A 69-year-old-female with type I GD presented with a left sixth nerve palsy due to a large posterior inferior cerebellar artery (PICA) aneurysm. Cerebral angiography demonstrated fifteen unruptured IAs (UIAs).

Evaluation of a fixed, weight-based dose of 3-factor prothrombin complex concentrate without adjunctive plasma following warfarin-associated intracranial hemorrhage.

INTRODUCTION: Data regarding use of prothrombin complex concentrate (PCC) for international normalization ratio (INR) reversal in warfarin-associated intracranial hemorrhage (wICH) is variable with regards to dosages, adjunctive agents, and product choice. In 2012, we implemented a fixed, weight-based [30 IU/kg] dosing protocol of 3-factor PCC (3PCC) utilizing a rapid infusion rate and no requirement for fresh frozen plasma (FFP) following factor product administration. We aimed to evaluate the impact of this protocol on immediate and delayed INR reversal in patients admitted with wICH in the absence of FFP co-administration. METHODS: We conducted a retrospective review of patients receiving 3PCC following wICH between January 1, 2012 and December 10, 2013. The primary objective was to determine the percentage of patients achieving goal INR (≤1.4) following 3PCC administration. Patients were excluded if their bleed was not intracranial in origin, received a dose outside of the specified protocol, or were given FFP as an adjunctive agent. RESULTS: We included 35 patients with a mean presenting INR of 3.2 ± 1.3. Thirty patients (85.7%) achieved goal INR (≤1.4) following one dose of 3PCC. The mean INR after infusion of 3PCC was 1.3 ± 0.2. The median duration between 3PCC infusion and subsequent INR was 48.0 min (30-70.1 min). Vitamin K was utilized in 33 (94.3%) patients. No patient experienced a thromboembolic event within 7 days of 3PCC administration. CONCLUSIONS: Fixed, weight-based dosing of 3PCC without adjunctive FFP resulted in high rates of complete INR reversal without significant adverse events.

The STAT3-Regulated Autophagy Pathway in Glioblastoma.

Glioblastoma (GBM) is the most common primary brain malignancy in adults with a dismal prognosis. Despite advances in genomic analysis and surgical technique and the development of targeted therapeutics, most treatment options are ineffective and mainly palliative. Autophagy is a form of cellular self-digestion with the goal of recycling intracellular components to maintain cell metabolism. Here, we describe some recent findings that suggest GBM tumors are more sensitive to the excessive overactivation of autophagy leading to autophagy-dependent cell death. GBM cancer stem cells (GSCs) are a subset of the GBM tumor population that play critical roles in tumor formation and progression, metastasis, and relapse, and they are inherently resistant to most therapeutic strategies. Evidence suggests that GSCs are able to adapt to a tumor microenvironment of hypoxia, acidosis, and lack of nutrients. These findings have suggested that autophagy may promote and maintain the stem-like state of GSCs as well as their resistance to cancer treatment. However, autophagy is a double-edged sword and may have anti-tumor properties under certain conditions. The role of the STAT3 transcription factor in autophagy is also described. These findings provide the basis for future research aimed at targeting the autophagy-dependent pathway to overcome the inherent therapeutic resistance of GBM in general and to specifically target the highly therapy-resistant GSC population through autophagy regulation.

Cushing Disease: Medical and Surgical Considerations.

Cushing disease is a disorder of hypercortisolemia caused by hypersecretion of adrenocorticotropic hormone by a pituitary adenoma and is a rare diagnosis. Cushing disease presents with characteristic clinical signs and symptoms associated with excess cortisol, but diagnosis is difficult and often relies on repeated and varied endocrinologic assays and neuroradiologic investigations. Gold standard treatment is surgical resection of adrenocorticotropic hormone-secreting pituitary adenoma, which is curative. Patients require close endocrinologic follow-up for maintenance of associated neuroendocrine deficiencies and surveillance for potential recurrence. Medications, radiation therapy, and bilateral adrenalectomy are alternative treatments for residual or recurrent disease.

High-Grade Sarcoma Arising within a Previously Irradiated Vestibular Schwannoma: A Case Report and Literature Review.

BACKGROUND: Vestibular schwannomas are benign tumors of the cerebellopontine angle that are often treated with radiation therapy. Radiation therapy maintains good tumor control rates but involves a small risk of radiation-induced malignancies. We present a case of high-grade sarcoma arising within a previously irradiated vestibular schwannoma and a literature review of this rare but important clinical entity. METHODS: A 66-year-old woman presented with rapid clinical and radiographic deterioration 17 years after receiving stereotactic radiosurgery for vestibular schwannoma. After resection, pathology revealed a high-grade sarcoma arising within a conventional schwannoma. After further decline and tumor growth, the patient died of her disease 7 months postoperatively. Literature review was performed using PubMed and EMBASE databases and key words "vestibular schwannoma," "acoustic," "triton," "malignant," "sarcoma," "malignant peripheral nerve sheath tumor," "radiation," and "radiosurgery." All previous cases and the clinical circumstances related to these radiation-induced malignancies were assessed and quantified. RESULTS: The systematic review yielded 20 prior cases of radiation-induced malignant transformation of a vestibular schwannoma in patients without neurofibromatosis. Most tumors (60%) transformed into malignant nerve sheath tumors. At the time of presentation, 70% of patients had new cranial neuropathies, and all had evidence of tumor growth with brainstem compression. Prognosis was poor with mean time to death of 7.6 months. CONCLUSIONS: Radiation-induced malignant transformation of vestibular schwannomas is a rare but important clinical entity. Given its scarcity, the risk of malignancy should not sway initial management, but rapid clinical deterioration and radiographic growth during follow-up should prompt consideration of malignant transformation.

Fusiform dilatation of the internal carotid artery following childhood craniopharyngioma resection treated by endovascular flow diversion-A case report and literature review.

Fusiform dilatation of the internal carotid artery (FDICA) is a well-described radiographic finding following resection of childhood craniopharyngioma (CP). A 39-year-old woman with right-sided FDICA was successfully treated for lesion enlargement with endovascular flow diversion, which has not been described in the literature.

The Role of Intraoperative Cerebral Angiography in Transorbital Intracranial Penetrating Trauma: A Case Report and Literature Review.

BACKGROUND: Transorbital intracranial penetrating trauma with a retained intracranial foreign body is a rare event lacking a widely accepted diagnostic and therapeutic algorithm. Intraoperative catheter angiography (IOA) has been advocated by some authorities to rule out cerebrovascular injury before and/or after removal of the object, but no standard of care currently exists. CASE DESCRIPTION: A 19-year-old man was involved in a construction site accident whereby a framing nail penetrated the left globe, traversed the lateral bony orbit, and terminated in the midtemporal lobe. No hematoma or injury to the middle cerebral arteries (MCAs) was apparent on noncontrast head computed tomography (CT) or CT angiography, respectively. The foreign body was removed in the operating room under direct visualization after a frontotemporal craniotomy without incident. No significant venous or arterial bleeding was encountered. All visualized MCA branches appeared intact. Indocyanine green videoangiography performed immediately after object removal showed adequate filling of the MCA branches. Given these uneventful clinical and radiographic findings, IOA was not performed. Postoperative head CT and CT angiography showed no obvious neurovascular injury. On postoperative day 2, the patient was noted to have an expressive aphasia. Cerebral angiography showed absent antegrade filling of the angular artery with some retrograde perfusion. Magnetic resonance imaging confirmed an ischemic infarction in the midtemporal lobe. The patient's expressive aphasia improved to near baseline during his hospitalization and he made an excellent clinical recovery. CONCLUSIONS: In transorbital intracranial penetrating trauma with a retained intracranial object, we advocate microsurgical removal of the object under direct visualization followed immediately by IOA. IOA should be strongly considered even in the setting of minimal intraoperative bleeding and normal findings on videoangiography (a course of action that was not followed in the present case). Given that CT angiography and intraoperative videoangiography may miss a potentially treatable traumatic arterial injury, IOA can help determine whether cerebral revascularization may be necessary.

Subacute Posttraumatic Ascending Myelopathy After an Incomplete Spinal Cord Injury from a Gunshot Wound to the Spine: Case Report and Review of the Literature.

BACKGROUND: Subacute posttraumatic ascending myelopathy (SPAM) is a rare event that occurs after spinal cord trauma or ischemia. SPAM is defined as progressive loss of spinal cord or nerve root function days to weeks after the initial trauma that cannot be attributed to mechanical instability. Because of the rarity of this condition, there is no clear understanding of its cause, natural history, or treatment guidelines for patient management. CASE DESCRIPTION: Here, we present the first reported case of SPAM after a gunshot wound to the spine. In this case, the patient presented with a mild spinal cord injury that recovered after surgery but then progressed to a more severe spinal cord injury many days later. Magnetic resonance imaging before and after his new symptoms supported the diagnosis of SPAM. CONCLUSIONS: This case demonstrates that spinal cord injury is a dynamic lesion, both in the immediate postinjury stage and in the subacute time interval as well. This is the first reported case of SPAM that occurred after the resolution of incomplete SCI and only the second that occurred after a gunshot wound.

Dietary habits and leisure-time physical activity in relation to adiposity, dyslipidemia, and incident dysglycemia in the pathobiology of prediabetes in a biracial cohort study.

BACKGROUND: Dietary and exercise data are frequently recorded in clinical research, but their correlation with metabolic measures needs further evaluation. OBJECTIVE: We examined the association of food and exercise habits with body size, lipid profile, and glycemia in a prospective biracial cohort. METHODS: The Pathobiology of Prediabetes in A Biracial Cohort study followed initially normoglycemic offspring of parents with type 2 diabetes (T2DM) for the occurrence of incident prediabetes, defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). At enrollment, participants underwent a 75-gram OGTT, anthropometry, measurement of fasting lipids, insulin, and body fat (DEXA), and completed the Food Habits Questionnaire (FHQ), and Modifiable Activity Questionnaire (MAQ). We assessed the relationship between FHQ and MAQ scores and adiposity, cardiometabolic measures, and incident dysglycemia. RESULTS: Among our cohort of 338 subjects (188 black, 150 white; mean age {±SD} 45.2±10.2 years, BMI 30.3±7.2 kg/m(2)), FHQ and MAQ scores were individually correlated with BMI (r=0.14, -0.12; P=0.01, 0.03) and waist circumference (r=0.19, -0.11; P=0.004, 0.05). Diet-adjusted leisure activity (MAQ/FHQ) was significantly correlated with total body fat (r=-0.20, P=0.0007), trunk fat (r=-0.20, P=0.0006), and serum triglycerides (r=-0.17, P=0.003) and HDL cholesterol (r=0.11, P=0.04) levels. During 5.5 years of follow-up, 111 subjects (Progressors) developed prediabetes (n=101) or diabetes (n=10) and 227 remained normoglycemic (Non-progressors). Age, BMI, MAQ and MAQ/FHQ values were significant predictors of incident prediabetes/diabetes. Progressors reported similar dietary habits (FHQ score 2.57±0.49 vs. 2.57±0.53) but 30% lower physical activity (MAQ score 15.2±20.5 vs. 22.3±30.5 MET-hr/wk, P=0.015) compared with non-progressors. CONCLUSIONS: Among African-American and Caucasian offspring of parents with T2DM, self-reported dietary and exercise habits correlated with measures of adiposity and dyslipidemia; however, physical activity, but not dietary recall, significantly predicted incident dysglycemia during 5.5 years of follow-up.

The middle fossa approach for the removal of a trochlear schwannoma.

Objectives. Schwannomas originating from the trochlear nerve are extremely rare; only 30 cases have been reported in the literature. Many operative approaches have been utilized for lesion resection, but the advantages of the anterior transpetrosal approach are numerous and include excellent exposure, minimal extradural retraction of the temporal lobe, and minimal cerebrospinal fluid leaks. We report the second case of a trochlear schwannoma resected via the anterior transpetrosal approach. Setting. A 64-year-old male presented with 3-month history of diplopia and headaches. On physical examination, he was found to have a right fourth nerve palsy. Brain magnetic resonance imaging revealed a mass within the right ambient cistern compressing the adjacent midbrain. A right-sided anterior transpetrosal approach was used-which confirmed that the trochlear nerve entered the mass-to achieve gross total resection. Pathological examination confirmed diagnosis of schwannoma. The patient was discharged on postoperative day 3. He experienced a persistent fourth nerve palsy postoperatively with an otherwise normal neurological examination. Follow-up imaging confirmed complete removal of the tumor. Conclusion. The anterior transpetrosal approach is an excellent approach for removal of trochlear schwannomas involving the cisternal course of the trochlear nerve. It affords complete visualization of this anatomical region while introducing minimal morbidity.

Effectiveness of pseudoephedrine as adjunctive therapy for neurogenic shock after acute spinal cord injury: a case series.

STUDY OBJECTIVE: To evaluate the effectiveness of pseudoephedrine as adjunctive therapy for neurogenic shock in patients with acute spinal cord injury (SCI). DESIGN: Case series. SETTING: Academic medical center. PATIENTS: Thirty-eight patients admitted to the trauma intensive care unit between September 2005 and October 2012 with an acute SCI and who received more than 1 day of pseudoephedrine for one or more of the following: treatment of bradycardia (heart rate ≤ 50 beats/min), treatment of hypotension (systolic blood pressure < 90 mm Hg), or were receiving intravenous vasopressor support. MEASUREMENTS AND MAIN RESULTS: The effect of adjunctive pseudoephedrine (PSE) was categorized as a success if vasopressors were discontinued after the initiation of PSE or improvement in the number of episodes of bradycardia was noted after the initiation of PSE as evidenced by decreased use of atropine. The effect of pseudoephedrine was categorized as a failure if it did not meet one of the criteria for success. The effect of pseudoephedrine was categorized as inconclusive if there were confounding factors such as vasopressors being restarted for another indication after initial discontinuation. Pseudoephedrine was successful in 31/38 (82%) patients, failed in 2/38 (5%) patients, and had inconclusive results in 5/38 (13%) patients. The mean ± SD time to successful weaning of intravenous vasopressors was 7 ± 7 days. Daily maximum pseudoephedrine doses ranged from 60-720 mg. Mean ± SD duration of pseudoephedrine therapy was 32 ± 23 days (range 2-135 days), with 64.5% of surviving patients discharged while receiving pseudoephedrine. CONCLUSION: These data suggest that pseudoephedrine is an effective adjunctive therapy in facilitating the discontinuation of intravenous vasopressors and/or atropine in patients with acute SCI with neurogenic shock, although patients will typically require long durations of therapy.