Cavernous malformations of the central nervous system: An international consensus statement.

Introduction: Cavernous malformations (CM) of the central nervous system constitute rare vascular lesions. They are usually asymptomatic, which has allowed their management to become quite debatable. Even when they become symptomatic their optimal mode and timing of treatment remains controversial. Research question: A consensus may navigate neurosurgeons through the decision-making process of selecting the optimal treatment for asymptomatic and symptomatic CMs. Material and methods: A 17-item questionnaire was developed to address controversial issues in relation to aspects of the treatment, surgical planning, optimal surgical strategy for specific age groups, the role of stereotactic radiosurgery, as well as a follow-up pattern. Consequently, a three-stage Delphi process was ran through 19 invited experts with the goal of reaching a consensus. The agreement rate for reaching a consensus was set at 70%. Results: A consensus for surgical intervention was reached on the importance of the patient's age, symptomatology, and hemorrhagic recurrence; and the CM's location and size. The employment of advanced MRI techniques is considered of value for surgical planning. Observation for asymptomatic eloquent or deep-seated CMs represents the commonest practice among our panel. Surgical resection is considered when a deep-seated CM becomes symptomatic or after a second bleeding episode. Asymptomatic, image-proven hemorrhages constituted no indication for surgical resection for our panelists. Consensus was also reached on not resecting any developmental venous anomalies, and on resecting the associated hemosiderin rim only in epilepsy cases. Discussion and conclusion: Our Delphi consensus provides an expert common practice for specific controversial issues of CM patient management.

Sellar/Suprasellar Ganglioglioma: Clinical Image.

BACKGROUND: This report presents a rare presentation of a ganglioglioma in the sellar/suprasellar region. On the basis of the patient's presentation and imaging characteristics, the initial diagnosis was craniopharyngioma. While gangliogliomas are already rare brain tumors that are usually found in the frontal and temporal lobes of young patients, the presentation of this tumor in the sellar region is exceedingly rare. CASE DESCRIPTION: A 25-year-old male presented to the emergency department with headache, agitation, and combativeness. A head computed tomography scan showed a sellar/suprasellar mass with mixed solid and cystic components and peripheral calcifications. The mass compressed the third ventricle and cerebral aqueduct, resulting in obstructive hydrocephalus. The patient was intubated for decline in mental status and combativeness. A ventricular drain was placed emergently. A pituitary function panel did not show endocrine dysfunction. Magnetic resonance imaging showed a 3.6 cm × 4.2 cm solid mass in the sellar/suprasellar region with a cystic component. The mass displaced the adenohypophysis and extended into the prepontine and interpedicular cisterns. The clinical presentation and radiologic characteristics led to an initial diagnosis of craniopharyngioma. The patient underwent a right pterional craniotomy and transsylvian approach for resection of mass without complication, although a subtotal resection was achieved due to adherence of the tumor to optic nerves and carotid arteries. The resected specimen was diagnosed as ganglioglioma. CONCLUSIONS: This case is a reminder of how much the field of neurosurgery relies on imaging modalities but also emphasizes the importance of histopathology in the field of brain tumors.

A Retrospective Cohort Analysis of Hemorrhagic Arteriovenous Malformations Treated with Combined Endovascular Embolization and Gamma Knife Stereotactic Radiosurgery.

BACKGROUND: The management of brain arteriovenous malformations (AVMs) remains a controversial topic. Given the relatively low incidence, high heterogeneity, and high morbidity and mortality of these lesions, consensus on treatment strategies is an issue of concern to organized neurosurgery. The present retrospective analysis examined and quantified the outcomes of patients with an initial presentation of intracranial hemorrhage from a Spetzler-Martin grade III or IV AVM, later ruled out as surgical candidates. METHODS: A total of 16 patients (5 females; 11 males) had presented with symptomatic hemorrhage confirmed by non-contrast-enhanced computed tomography and were deemed to not be surgical candidates owing to AVM location and/or architecture. The patients underwent combined endovascular embolization and gamma knife stereotactic radiosurgery (SRS). The modified Rankin scale was used to measure the clinical outcomes, comparing the scores at presentation, gamma knife treatment, and the last known follow-up examination. A radiographic evaluation was used to determine the level of AVM nidus involution after the procedure. RESULTS: The present study identified 16 patients with ruptured high-grade AVMs of high surgical risk. All the patients had undergone immediate embolization with delayed SRS for treatment of the hemorrhage and nidus of the AVM. A statistically significant proportion of patients showed marked improvement in the modified Rankin scale scores. No subsequent repeat hemorrhage or any associated complications after embolization occurred in any patient. CONCLUSION: These findings warrant consideration of endovascular embolization with adjuvant SRS as a powerful treatment option for cases with high surgical morbidity due to AVM characteristics.

Remote ischemic post-conditioning promotes hematoma resolution via AMPK-dependent immune regulation.

Spontaneous intracerebral hemorrhage (ICH) produces the highest acute mortality and worst outcomes of all stroke subtypes. Hematoma volume is an independent determinant of ICH patient outcomes, making clot resolution a primary goal of clinical management. Herein, remote-limb ischemic post-conditioning (RIC), the repetitive inflation-deflation of a blood pressure cuff on a limb, accelerated hematoma resolution and improved neurological outcomes after ICH in mice. Parabiosis studies revealed RIC accelerated clot resolution via a humoral-mediated mechanism. Whereas RIC increased anti-inflammatory macrophage activation, myeloid cell depletion eliminated the beneficial effects of RIC after ICH. Myeloid-specific inactivation of the metabolic regulator, AMPKα1, attenuated RIC-induced anti-inflammatory macrophage polarization and delayed hematoma resolution, providing a molecular link between RIC and immune activation. Finally, chimera studies implicated myeloid CD36 expression in RIC-mediated neurological recovery after ICH. Thus, RIC, a clinically well-tolerated therapy, noninvasively modulates innate immune responses to improve ICH outcomes. Moreover, immunometabolic changes may provide pharmacodynamic blood biomarkers to clinically monitor the therapeutic efficacy of RIC.

Acute spontaneous intracranial epidural haematoma and disseminated intravascular coagulation in a paediatric sickle cell patient.

An African American teenage boy during an acute sickle cell crisis spontaneously developed acute bifrontal epidural haematomas (EDHs) in addition to disseminated intravascular coagulation (DIC). The successfully evacuated EDH reaccumulated postoperatively. After multiple transfusions, the patient underwent repeat surgery. Subsequent maximal medical therapy was unable to significantly improve the patient's neurological status, and due to family wishes, care was withdrawn. EDH are the most common emergent neurosurgical complication of sickle cell disease (SCD). Twenty-two such cases have been previously reported. We present one further complicated by DIC leading to reaccumulation of the patient's EDH. An understanding of the mechanisms of EDH formation in SCD and their associated radiological findings could help clinicians identify when a patient is at high risk of EDH formation and thus offer the potential for early intervention prior to the development of an emergency.

Cephalad Migration of Intradural Bullet from Thoracic Spine to Cervical Spine.

BACKGROUND: There are few reported instances of intraspinal migration of a bullet fragment. The majority of these migrations occur caudally, typically below the level of T10. Even fewer cases demonstrate cephalad migration from the sacral spine to the lumbar spine. We report here for the first time a case of a cephalad migration intradurally from the thoracic spine to cervical spine. CASE DESCRIPTION: A 31-year old man presented to the emergency department with a suspected spinal cord injury following a GSW sustained to the left shoulder. A penetrating gunshot injury to the thoracic spine at the level of T2 was observed, and CT angiography revealed a cephalad migration of the bullet fragment to the level of C6. The patient had marked weakness of the bilateral upper extremities, with paraplegia of the lower extremities. There was a sensory deficit beginning at a level 1 cm below the clavicle, as well as a decrease in rectal tone. We performed a laminectomy at C6 with dural incision and removal of the main bullet fragment. Following the surgery, significant improvement in strength and sensation in the bilateral upper extremities was noted, but paraplegia and sensory loss below the level of T2 persisted. CONCLUSIONS: In this report, we review the previously reported cases in which intraspinal migration of bullets have occurred, and discuss the unique finding in this study of cephalad migration of a bullet within the dura. In addition, we detail considerations in the management of such injuries.

Suprasellar Ganglioglioma: Expanding the Differential Diagnosis.

This case study describes a young man with symptoms suggestive of the presence of a space-occupying lesion within the cranial cavity. Imaging studies confirmed a lesion in the suprasellar region and surgical intervention to remove the tumor yielded an unexpected diagnosis. Neuroimaging characteristics and histopathology including immunohistochemistry are described. Gangliogliomas are uncommon CNS neoplasms and are most commonly found in the temporal and frontal lobes of young, male adults. They are rarely seen in the suprasellar region and only a handful of cases have been reported to date. The differential diagnoses associated with these suprasellar region lesions can be dependent on the age of the patient and neuroimaging characteristics. The present report highlights the importance of histopathological examination and the need to consider a wide range of diagnostic entities in the differential diagnosis of lesions in this topographic distribution, including rarely encountered tumors such as gangliogliomas.

Anterior Gray Matter Pituicytic Heterotopia with Monomorphic Anterior Pituitary Cells: A Variant of Nonsecretory Pituitary Adenoma Neuronal Choristoma? Report of a Rare Case and Review of the Literature.

BACKGROUND: Mixed tumors of adenomatous and neuronal cells in the sellar region are an uncommon finding. The origins of these heterogeneous tumors are unknown, and management remains unsettled. We report a very rare case of anterior gray matter pituicytic heterotopia with monomorphic anterior pituitary cells that likely represents a variant of nonsecreting pituitary adenoma neuronal choristoma (PANCH) with no ganglion cells. We also review the current literature for the various clinical presentations of PANCH. CASE DESCRIPTION: A 49-year-old female complaining of headache, blurred vision, and hair loss was found to have a nonsecretory sellar mass with compression of the optic chiasm on magnetic resonance imaging (MRI). The mass was excised via a transsphenoidal procedure. Histological analysis of tissue sections revealed heterotopic gray matter with reactive gliosis without ganglion cells or Herring bodies. Only 1 smear exhibited characteristics of a pituitary adenoma. CONCLUSIONS: The overall findings were most consistent with a variant of PANCH. At a postoperative follow-up of 4.5 years, there was resolution of visual symptoms, and the residual sellar mass was stable on MRI. Neuronal choristoma is hypothesized to originate from embryonal pituitary or hypothalamus, or by differentiation from pituitary adenoma cells. Surgery is the cornerstone of management, and the clinical course appears to be similar to that of nonfunctioning pituitary adenoma in reported cases.

Overexpression of Nrf2 attenuates Carmustine-induced cytotoxicity in U87MG human glioma cells.

BACKGROUND: Malignant glioma is one of the most devastating tumors in adults with poor patient prognosis. Notably, glioma often exhibits resistance to conventional chemotherapeutic approaches, complicating patient treatments. However, the molecular mediators involved in tumor chemoresistance remain poorly defined, creating a barrier to the successful management of glioma. In the present study, we hypothesized that the antioxidant transcription factor, Nrf2 (nuclear factor erythroid-derived 2 like 2), attenuates glioma cytotoxicity to Carmustine (BCNU), a widely used chemotherapeutic agent known to modulate cellular oxidative balance. METHODS: To test the hypothesis, we employed human malignant glioma cell line, U87MG and overexpression of Nrf2 in glioma cells was achieved using both pharmacological and genetic approaches. RESULTS: Notably, induction of Nrf2 was associated with increased expression of heme oxygenase-1 (HO-1), a stress inducible enzyme involved in anti-oxidant defense. In addition, over expression of Nrf2 in U87MG cells significantly attenuated the cytotoxicity of Carmustine as evidenced by both cellular viability assay and flow cytometry analysis. Consistent with this, antioxidants such as glutathione and N-acetyl cysteine significantly reduced Carmustine mediated glioma cytotoxicity. CONCLUSIONS: Taken together, these data strongly implicate an unexplored role of Nrf2 in glioma resistance to Carmustine and raise the possible use of Nrf2 inhibitors as adjunct to Carmustine for the treatment of malignant glioma.

Neurosurgery at Medical College of Georgia, Georgia Regents University in Augusta (1956-2013).

: The neurosurgery service at the Medical College of Georgia, Georgia Regents University at Augusta has a rich history spanning almost 6 decades. Here, we review the development of neurological surgery as a specialty in Augusta and the history of the Department of Neurosurgery at Georgia Regents University. This article describes some of the early neurosurgeons in the city and those who have contributed to the field and helped to shape the department. Our functional and stereotactic program is emphasized. Our surgical epilepsy program dates back more than a half-century and remains a highly experienced program. We also describe our affiliation with the medical illustration graduate program, which was the first to be accredited and remains 1 of 4 such programs in the world. Finally, we list our alumni, former faculty, and current faculty, as well as the major accomplishments in our first decade as a full department.

Teaching neuroimages: microvascular decompression of the optic nerve.

Vascular compression is a known cause of cranial nerve dysfunction in a variety of disease states including trigeminal neuralgia, hemifacial spasm, and hypoglossal neuralgia.(1,2.)

Bilateral transverse sinus stenosis causing intracranial hypertension.

Idiopathic intracranial hypertension (IIH) has been associated with transverse sinus stenosis in a number of cases. Some authors advocate for stent placement when transverse sinus stenosis is responsible for pseudotumor symptoms. A 19-year-old man with IIH, bilateral transverse sinus stenosis was apparent on a CT venography, with reconstitution of the lateral sinus. MRI was then performed, and transverse sinus stenosis was confirmed. An impressive network of dilated collateral veins became apparent on VENBOLD sequences. Treatment options in this case include cerebrospinal fluid (CSF) shunting, optic nerve fenestrations and transverse sinus stenting. A ventriculoperitoneal shunt was placed in this patient, with prompt resolution of pseudotumor symptoms.

TNF-alpha receptor antagonist, R-7050, improves neurological outcomes following intracerebral hemorrhage in mice.

Intracerebral hemorrhage (ICH), the most common form of hemorrhagic stroke, exhibits the highest acute mortality and the worst long-term prognosis of all stroke subtypes. Unfortunately, treatment options for ICH are lacking due in part to a lack of feasible therapeutic targets. Inflammatory activation is associated with neurological deficits in pre-clinical ICH models and with patient deterioration after clinical ICH. In the present study, we tested the hypothesis that R-7050, a novel cell permeable triazoloquinoxaline inhibitor of the tumor necrosis factor receptor (TNFR) complex, attenuates neurovascular injury after ICH in mice. Up to 2h post-injury administration of R-7050 significantly reduced blood-brain barrier opening and attenuated edema development at 24h post-ICH. Neurological outcomes were also improved over the first 3 days after injury. In contrast, R-7050 did not reduce hematoma volume, suggesting the beneficial effects of TNFR inhibition were downstream of clot formation/resolution. These data suggest a potential clinical utility for TNFR antagonists as an adjunct therapy to reduce neurological injury and improve patient outcomes after ICH.

Open surgical management of a ruptured intracranial aneurysm in Klippel-Trenaunay-Weber (KTW) syndrome.

A 24-year-old man with a history of Klippel-Trenaunay-Weber syndrome presented with severe headache and neck pain. Work-up revealed subarachnoid hemorrhage and evidence of multiple intracranial aneurysms. The patient was treated with open surgical clipping of his ruptured aneurysm and is currently doing well.

Astrocyte-specific expression of survivin after intracerebral hemorrhage in mice: a possible role in reactive gliosis?

Intracerebral hemorrhage (ICH), the most common form of hemorrhagic stroke, accounts for up to 15% of all strokes. Despite maximal surgical intervention and supportive care, ICH is associated with significant morbidity and mortality, in part due to a lack of viable treatment options. Astrogliosis, a key feature of secondary injury that is characterized by glial proliferation, is a poorly-defined process that may produce both beneficial and detrimental outcomes after brain injury. Using a pre-clinical murine model of collagenase-induced ICH, we demonstrate a delayed upregulation of survivin, a key molecule involved in tumor cell proliferation and survival, by 72 h post-ICH. Notably, this increase in survivin expression was prominent in GFAP-positive astrocytes, but absent in neurons. Survivin was not expressed at detectable levels in the striatum of sham-operated mice. The expression of survivin after ICH was temporally and spatially associated with the expression of proliferating cell nuclear antigen (PCNA), an established marker of cellular proliferation. Moreover, the survivin expression was co-localized in proliferating astrocytes as evidenced by triple-label immunohistochemistry. Finally, shRNA-mediated silencing of survivin expression attenuated PCNA expression and reduced cellular proliferation in human glial cells. Together, these data suggest a potentially novel role for survivin in functionally promoting astrocytic proliferation after ICH.

Unusual case of subarachnoid haemorrhage in patient with Fabry's disease: case report and literature review.

Fabry's disease is a rare, X linked recessive disease affecting 1 in 40 000 persons. The symptoms result from a lack of or a non-functioning enzyme α galactosidase, which leads to globotriaosylceramide accumulation in the walls of blood vessels. Mortality is generally from cardiac or renal complications and death from subarachnoid haemorrhage is distinctly rare. The authors report a man with Fabry's disease who died after subarachnoid haemorrhage from a progressively enlarging fusiform basilar aneurysm.

Rare giant traumatic cervical arteriovenous fistula in neurofibromatosis type 1 patient.

Arteriovenous fistulas can rarely occur in patients with neurofibromatosis type 1. These lesions typically result from traumatic insult to the dysplastic parent artery. The damaged artery forms abnormal connections with nearby paraspinal and epidural venous structures. Surgical treatment of these lesions can be extremely challenging given the proximity to the spinal cord and the ability of the fistula to recruit vessels from adjacent vascular structures. A 29-year-old woman with neurofibromatosis type 1 and a motor vehicle collision 2 years earlier presented with gait difficulty, lower extremity spasticity and neck and arm pain. Her investigation revealed a giant cervical vertebral arteriovenous fistula. The fistula was successfully treated in multiple stages using all endovascular techniques including detachable coils, stents and glue embolisation. Reduction in flow and improvement in symptoms are reasonable goals in this specific rare subgroup of complex cervical arteriovenous fistulae.