Pemetrexed in the treatment of relapsed/refractory primary central nervous system lymphoma.

BACKGROUND: Despite initial treatment with high-dose methotrexate-based regimens, many patients with primary central nervous system lymphoma (PCNSL) relapse and die from their disease. No standard of care exists at progression or relapse, but chemotherapy and in some cases radiation are usually used. Pemetrexed is a multitargeted antifolate, similar to methotrexate, but with a broader spectrum of activity. Because methotrexate is an integral part of PCSNL treatment, the authors assessed the antitumor activity and safety of pemetrexed in recurrent PCNSL. METHODS: Patients with relapsed/refractory PCNSL were enrolled in this trial. Treatment consisted of pemetrexed 900 mg/m(2) given every 3 weeks with low-dose dexamethasone, folate, and B12 supplementation. Each cycle was 6 weeks, and follow-up imaging was done before each new cycle. Treatment was continued until complete remission, progression, or toxicity. RESULTS: Eleven patients were treated, with a median age of 69.8 years and Karnofsky performance status of 70%; 10 of 11 patients had failed prior high-dose methotrexate. The median number of pemetrexed cycles given was 5, with an associated overall response rate of 55% and disease control rate of 91%. The 6-month progression-free survival (PFS) was 45%, median PFS was 5.7 months, and median overall survival was 10.1 months. Toxicities were primarily hematologic and infectious. CONCLUSIONS: Pemetrexed has single-agent activity in relapsed/refractory PCNSL. Toxicities were seen likely because of the higher than standard dose used. Further investigation of this agent or other multitargeted antifolates in PCNSL is warranted to determine optimal dose and efficacy in a more homogeneous population.

A national fundamentals curriculum for neurosurgery PGY1 residents: the 2010 Society of Neurological Surgeons boot camp courses.

BACKGROUND: In July 2009, the Accreditation Council for Graduate Medical Education (ACGME) incorporated postgraduate year 1 (PGY1 intern) level training into all U.S. neurosurgery residency programs. OBJECTIVE: To provide a fundamentals curriculum for all incoming neurosurgery PGY1 residents in ACGME-accredited programs, including skills, knowledge, and attitudes that promote quality, patient safety, and professionalism. METHODS: The Society of Neurological Surgeons organized 6 regional "boot camp" courses for incoming neurosurgery PGY1 residents in July 2010 that consisted of 9 lectures on clinical and nonclinical competencies plus 10 procedural and 6 surgical skills stations. Resident and faculty participants were surveyed to assess knowledge and course effectiveness. RESULTS: A total of 186 of 197 U.S. neurosurgical PGY1 residents (94%) and 75 neurosurgical faculty from 36 of 99 programs (36%) participated in the inaugural boot camp courses. All residents and 83% of faculty participants completed course surveys. All resident and faculty respondents thought that the boot camp courses fulfilled their purpose and objectives and imparted skills and knowledge that would improve patient care. PGY1 residents' knowledge of information taught in the courses improved significantly in postcourse testing (P < .0001). Residents and faculty particularly valued simulated and other hands-on skills training. CONCLUSION: Regional organization facilitated an unprecedented degree of participation in a national fundamental skills program for entering neurosurgery residents. One hundred percent of resident and faculty respondents positively reviewed the courses. The boot camp courses may provide a model for enhanced learning, professionalism, and safety at the inception of training in other procedural specialties.

True aneurysm on the posterior meningeal artery associated with a dural arteriovenous fistula: case report.

BACKGROUND: We report an unusual case of a true dural aneurysm arising from the posterior meningeal artery that fed a symptomatic dural arteriovenous fistula located at the right transverse-sigmoid sinus junction. CLINICAL PRESENTATION: A 29-year-old right-handed white woman presented with aneurysmal dilatation of hypertrophied posterior meningeal artery feeding a partially treated dural arteriovenous fistula. INTERVENTION: The aneurysm, which measured approximately 3 mm in width and 5 mm in length, was located in the intracranial space with a thin-walled dome projecting toward the cerebellum. Its afferent and efferent vessels were identified, secured, and the lesion was excised en bloc. CONCLUSION: A thorough evaluation of all diagnostic studies should be performed for patients with vascular malformations to help identify these or other unusual lesions that may aid in the risk stratification process and management plan.

Posterior fossa arteriovenous malformations.

Arteriovenous malformations (AVMs) of the posterior fossa are complex neurovascular lesions that are less common than their supratentorial counterparts, accounting for < 15% of all AVMs. The majority of patients with these lesions present with intracranial hemorrhage, a factor that has been consistently shown to increase one's risk for subsequent bleeding. Studies have additionally shown a posterior fossa or deep AVM location to portend a more aggressive natural history. The authors reviewed the literature on posterior fossa AVMs, finding their annual rupture rates to be as high as 11.6%, an important factor that underscores the importance of aggressive treatment of lesions amenable to intervention as therapeutic options and results continue to improve.

Genomics of human intracranial aneurysm wall.

BACKGROUND AND PURPOSE: The pathogenesis of intracranial aneurysms (IAs) remains elusive. Most studies have focused on individual genes, or a few interrelated genes or products, at a time in human IA. However, a broad view of pathologic mechanisms has not been investigated by identifying pathogenic genes and their interaction in networks. Our study aimed to analyze global gene expression patterns in the IA wall. METHODS: To our knowledge, our group was the first to perform Illumina microarray analysis on human IA via comparison of aneurysm wall and superficial temporal artery tissues from 6 consecutive patients. We adopted stringent statistical criteria to the individual genes; genes with a false discovery rate <0.01 and >2-fold change were selected as differentially expressed. To identify the overrepresented biologic pathways with the differentially expressed genes, we performed hypergeometric testing of the genes selected by relaxed criteria of P<0.01 and fold change >1.5. RESULTS: There are 326 distinct differentially expressed genes between IA and superficial temporal artery tissues (>2-fold change) with a false discovery rate <0.01. Analysis of the Kyoto Encyclopedia of Genes and Genomes pathways revealed the most impacted functional pathways: focal adhesion, extracellular matrix receptor interaction, and cell communication. Analysis of the Gene Ontology also supported the involvement of another 2 potentially important pathways: inflammatory response and apoptosis. CONCLUSIONS: The differentially expressed genes in the aneurysm wall may shed light on aneurysm pathobiology and provide novel targets for therapeutic intervention. These data will help generate hypotheses for future studies.

Acute symptomatic cerebellar tonsillar herniation following intraoperative lumbar drainage.

Complications of tonsillar herniation associated with lumbar drainage have been reported in the literature. However, acutely symptomatic tonsillar herniation after intraoperative lumbar drainage is rare. The following case illustrates the risk associated with cerebrospinal fluid (CSF) drainage in the setting of tonsillar herniation. The use of lumbar drainage during cranial surgery is a common practice for reducing intracranial pressure and enhancing exposure, but is not without complications. In addition to the complications of the insertion procedure itself, the change in pressure gradient between the intracranial and the suboccipital compartments is of key importance. The authors present the case of a patient who underwent a subtemporal craniotomy for resection of mesial temporal cavernous malformation with intraoperative lumbar drainage. The patient had a preexisting, asymptomatic 4-mm Chiari malformation and progressive neurological deficits resulting from further cerebellar tonsillar herniation in the early postoperative period developed, which required a lumbar blood patch, decompressive suboccipital craniectomy, and C-1 laminectomy with duroplasty. After placement of the lumbar drain and subsequent CSF drainage, the change in CSF pressure gradient above and below the foramen magnum probably led to the herniation. Unfortunately, the patient has lasting neuropathic pain and cervical cord signal changes on MR images.

Current updates in perioperative management of intracerebral hemorrhage.

Spontaneous intracerebral hemorrhages (ICH) account for 10% to 30% of all strokes and are a result of acute bleeding into the brain by rupturing of small penetrating arteries. Despite major advancements during the past several decades in the management of ischemic strokes and other causes of hemorrhagic strokes, such as ruptured aneurysm, arteriovenous malformations (AVMs), or cavernous angioma, there has been limited progress made in the treatment of ICH. The prognosis for patients who suffer intracerebral hemorrhage remains poor. The societal impact of these hemorrhagic strokes is magnified by the fact that affected patients typically are a decade younger than those afflicted with ischemic strokes.

Challenging traditional beliefs: microsurgery for arteriovenous malformations of the basal ganglia and thalamus.

OBJECTIVE: Arteriovenous malformations of the basal ganglia and thalamus are often managed with radiosurgery or observation, without consideration of microsurgery. Given the devastating effects of hemorrhage from these lesions, the accumulating evidence that they bleed more frequently than their lobar counterparts should prompt more creative thinking regarding their management. METHODS: A review of the endovascular, microsurgical, and radiosurgical literature for arteriovenous malformations of the basal ganglia and thalamus was performed, with close attention to surgical approaches, obliteration rates, and procedure-related complications. RESULTS: A complete resection rate of 91% and a mortality rate of 2.4% were found across surgical series of these lesions. These contrast with a 69% rate of complete obliteration and a 5.3% mortality rate (from latency-period hemorrhage) found when compiling results across the radiosurgical literature. CONCLUSION: Given an appropriate surgical corridor of access, often afforded by incident hemorrhage, arteriovenous malformations of the basal ganglia and thalamus should be considered for microsurgical extirpation with preoperative embolization. In experienced hands, this approach presents an expeditious and definitive opportunity to eliminate the risk of subsequent hemorrhage and resultant morbidity and mortality.

Surgical and endovascular treatments for intracranial aneurysms.

The goals of microsurgical and endovascular treatment of intracranial aneurysms are to prevent subarachnoid hemorrhage and/or eliminate mass effect symptoms. Debate has raged regarding which aneurysms to treat and with which technique or combination of techniques. It is our impression that studies that have assessed aneurysm natural history and treatment options are compromised by the inherent limitations of clinical trials, with many natural history studies likely underestimating rupture risk over long-term follow-up. Endovascular therapy and open neurosurgery should both be used strategically, and our current interest is in integrating these techniques in a fashion extending beyond the simplistic clip-versus-coil debate.

Advances in the radiosurgical treatment of large inoperable arteriovenous malformations.

Radiosurgery has proven useful in the treatment of small arteriovenous malformations (AVMs) of the brain. However, the volume of healthy tissue irradiated around large lesions is rather significant, necessitating reduced radiation doses to avoid complications. As a consequence, this can produce poorer obliteration rates. Several strategies have been developed in the past decade to circumvent dose-volume problems with large AVMs, including repeated treatments as well as dose, and volume fractionation schemes. Although success on par with that achieved in lesions smaller than 3 ml remains elusive, improvements over the obliteration rate, the complication rate or both have been reported after conventional single-dose stereotactic radiosurgery (SRS). Radiosurgery with a marginal dose or peripheral dose < 15 Gy rarely obliterates AVMs, yet most lesions diminish in size posttreatment. Higher doses may then be reapplied to any residual nidi after an appropriate follow-up period. Volume fractionation divides AVMs into smaller segments to be treated on separate occasions. Doses > 15 Gy irradiate target volumes of only 5-15 ml, thereby minimizing the radiation delivered to the surrounding brain tissue. Fewer adverse radiological effects with the use of fractionated radiosurgery over standard radiosurgery have been reported. Advances in AVM localization, dose delivery, and dosimetry have revived interest in hypofractionated SRS. Investigators dispensing >or= 7 Gy per fraction minimum doses have achieved occlusion with an acceptable number of complications in 53-70% of patients. The extended latency period between treatment and occlusion, about 5 years for emerging techniques (such as salvage, staged volume, and hypofractionated radiotherapy), exposes the patient to the risk of hemorrhage during that period. Nevertheless, improvements in dose planning and target delineation will continue to improve the prognosis in patients harboring inoperable AVMs.

Severe reversible cerebral vasoconstriction syndrome mimicking aneurysmal rupture and vasospasm.

INTRODUCTION: Presenting symptoms of aneurysmal subarachnoid hemorrhage (SAH) and reversible cerebral vasoconstriction syndrome (RCVS) may overlap. Patients with RCVS often harbor unruptured aneurysms. We report a case of RCVS in a patient with an unruptured intracranial aneurysm. The development of diffuse vasoconstriction after aneursym clipping in the absence of any subarachnoid blood was initially confusing, until subtle vasoconstriction before clipping was seen retrospectively. RESULTS: We obtained perfusion and diffusion MRI studies on this patient, which shed light on the pathophysiology of RCVS. CONCLUSION: It is important for physicians who care for patients with aneurysmal SAH to recognize RCVS, as the treatments for these two conditions are different.

Retrograde suction decompression of giant paraclinoid aneurysms using a No. 7 French balloon-containing guide catheter. Technical note.

The treatment of large and giant paraclinoid carotid artery (CA) aneurysms often requires the use of suction decompression for safe and effective occlusion. Both open and endovascular suction decompression techniques have been described previously. In this article the authors describe a revised endovascular suction decompression technique that provides several advantages in the treatment of large and giant paraclinoid and CA aneurysms. A 51-year-old woman presented with a relatively brief history of progressive visual loss in the right eye, nonspecific headache, and an afferent pupillary defect. After angiography studies had been obtained, it was determined that she had a giant right paraclinoid internal CA aneurysm with a dome size of approximately 26 mm on the right and a neck diameter of 10 mm. A modified technique was performed in which suction decompression was used. With the aid of a No. 7 French Concentric balloon guide catheter (Concentric Medical, Inc., Mountain View, CA) and application of a temporary clip distal to the aneurysm, the aneurysm was trapped and decompressed using retrograde suction through the guide catheter when the balloon was inflated. After satisfactory placement of three permanent clips, an intraoperative angiogram obtained through the same guide catheter confirmed CA patency. The aneurysm was then punctured and aspirated, ensuring complete occlusion of the aneurysm sac and reconstruction of the parent vessel. The patient made an excellent recovery and did not suffer any complications. She did not experience worsening in her vision. This technical modification to endovascular suction decompression allows several potential advantages, including higher volume decompression and the ability to deliver endovascular devices to distal arterial locations.

Current updates in perioperative management of intracerebral hemorrhage.

Spontaneous ICH remains a formidable disease that continues to disable and kill the majority of its victims. Treatment of the disease continues to be controversial and without any proved success, such as improvement in the disease mortality or the resulting disability in survivors. Primary prevention is the most effective medical intervention. Nevertheless, as the population continues to age and patients remain undertreated for hypertension, the incidence of ICH likely will increase, resulting in significant socioeconomic impact on society in the coming years. It is imperative that more research be conducted to improve treatment and outcomes of patients who have ICH. Unlike ischemic stokes or other causes of hemorrhagic stroke, such as SAH, where major advancement of treatment has led to improved outcomes, the increased incidence of ICH has not been matched with any considerable improvement in treatment. This burden to improve therapeutic interventions for patients who have ICH should be shared by all neurosurgeons, stroke neurologists, and critical care physicians who care for these patients on a regular basis. It is hoped that early diagnosis and resuscitation, prevention of hematoma growth, selective surgery or minimally invasive clot evacuation, and judicious critical care and rehabilitation will combine to lessen the burden of this disease.

Ruptured traumatic vertebral artery pseudoaneurysm in a child treated with trapping and posterior inferior cerebellar artery reimplantation. Case report and review of the literature.

The authors present the case report of a pediatric patient with a ruptured traumatic pseudoaneurysm of the intracranial vertebral artery (VA) from which the posterior inferior cerebellar artery (PICA) emerged. After considering multiple therapeutic options, the patient was treated surgically by trapping of the aneurysm segment and direct reimplantation of the PICA distal to the rupture site. In addition to presenting this unique case, the authors discuss the treatment of VA pseudoaneurysms and the various techniques for PICA revascularization. A review of the literature on PICA reimplantation is provided as an adjunct in the treatment of complex VA aneurysms.

Microsurgical resection of infratentorial arteriovenous malformations.

Successful microsurgical resection of an infratentorial arteriovenous malformation (AVM) requires both surgical skill and intraoperative judgment. Extensive practical experience in treating these complex lesions, which is acquired over many years, is of substantial value during each new operation. The authors present the surgical approaches and techniques used for the treatment of posterior fossa AVMs based largely on the strategies acquired and developed by the senior author (H.H.B.). Emphasis is placed on conceptual principles of AVM excision, as well as principles incorporated for the treatment of each specific type of infratentorial malformation.

Late morphological progression of a dissecting basilar artery aneurysm after staged bilateral vertebral artery occlusion: case report.

BACKGROUND: The authors present a patient who experienced late (5-year follow-up) morphological progression of a dissecting aneurysm of the distal basilar artery after treatment with a combined microsurgical and neuroendovascular Hunterian strategy. In addition to postulating about the possible reasons underlying the evolution of this lesion, the role of stenting is discussed. CASE DESCRIPTION: The patient was 37 years old when she suffered a subarachnoid hemorrhage from spontaneous basilar artery dissection. At the time of the hemorrhage, minimal aneurysmal enlargement was noted angiographically, and she was therefore treated nonoperatively. On reimaging 5 months later, massive enlargement of the aneurysm was noted. The patient was treated with staged bilateral vertebral artery sacrifice using a combination of microsurgical and neuroendovascular techniques. The dominant vertebral artery was clip-ligated distal to the posteroinferior cerebellar artery, whereas the contralateral vertebral artery was coil-occluded cervically 1 week later. CONCLUSIONS: Despite the patient remaining asymptomatic, follow-up angiography 5 years after the initial hemorrhage revealed further enlargement of the aneurysm as well as a newly discovered inferiorly projecting daughter sac measuring 5 mm in diameter. Clearly, certain aneurysms exist for which indirect approaches involving hemodynamic attenuation fail to prevent progression. With greater refinements in stent technology, such lesions may be more effectively treated.

Update on current registries and trials of carotid artery angioplasty and stent placement.

Stroke remains the leading cause of disability in adults and the third leading cause of death in the US. Carotid artery (CA) occlusive disease is the primary pathophysiological source of 10 to 20% of all strokes. Carotid endarterectomy (CEA) has been shown to reduce the risk of stroke in patients with both symptomatic and asymptomatic extracranial CA stenosis. Carotid artery angioplasty and stent placement has recently emerged as an alternative to CEA for primary and secondary prevention of stroke related to CA stenosis. With the advent of the embolic protection device, the safety of CA angioplasty and stent placement has approached, if not surpassed, that of CEA. In particular, the former has come to be considered as a first-line therapy in the management of CA stenotic disease in individuals at high risk for complications related to surgical intervention. Preliminary data from multiple registries have demonstrated that CA angioplasty and stent placement is an effective means of treating CA stenosis. The results of the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy trial have demonstrated that this modality has a significant role in the management of CA disease in symptomatic and asymptomatic patients with risk factors for high rates of surgery-related morbidity or mortality. With the completion of the Carotid Revascularization Endarterectomy versus Stent Trial, the role of CA angioplasty and stent placement in the prevention of stroke in all individuals with significant CA stenosis should be better demarcated. This treatment modality promises to assume a central role in stroke prophylaxis in patients with CA disease who are at high risk for complications related to surgery.