Endovascular Management of a Ruptured Basilar Perforator Artery Aneurysm Associated with a Pontine Arteriovenous Malformation: Case Report and Review of the Literature.

BACKGROUND: Arteriovenous malformation (AVM)-associated aneurysms are common, reported in 15% of cases. Regarding the ruptured posterior fossa AVMs, associated aneurysms are present in 48% of cases and are the cause of the bleed in 37%. We present a 75-year-old female who presented with a subarachnoid hemorrhage secondary to a ruptured aneurysm arising from a flow-related basilar perforator artery feeder of an anterior pontine AVM. We report the successful treatment of the aneurysm with coil embolization. CASE DESCRIPTION: A 75-year-old female presented with subarachnoid hemorrhage primarily contained within the posterior fossa. Angiography demonstrated a 2 × 3-mm fusiform aneurysm arising from a basilar perforator feeding pedicle of an anterior 1 × 2-cm pontine AVM. Venous drainage from the AVM was predominantly to the superior petrosal vein. Under roadmap guidance, super-selective catheterization of the basilar perforator aneurysm was performed. Three HydroSoft 3D coils were deployed within the aneurysm, resulting in complete obliteration. The patient was discharged on postbleed day 15 to an inpatient rehabilitation facility. Follow-up angiography at 5 months demonstrated stable complete obliteration. The patient made a complete recovery and was living independently at the time of this report. CONCLUSIONS: Basilar trunk perforator aneurysms are rare lesions, particularly in the setting of brainstem AVMs. We report successful endovascular treatment of a flow-related ruptured basilar perforator aneurysm associated with an anterior pontine AVM. To the best of our knowledge, this is the second report addressing this scenario. We hope that the information presented here serves to guide future surgical decision making and management.

Endovascular Management of Multiple Dysplastic Aneurysms in a Young Man with an Unknown Underlying Cause: A Case Report and Review of the Literature.

BACKGROUND: Intracranial aneurysms are the leading cause of nontraumatic subarachnoid hemorrhage and are most commonly associated with the anterior cerebral artery (ACA) and anterior communicating artery complex. We describe the presentation and management of a 27-year-old man with concurrent bilateral A1-2 junction aneurysms and fusiform intraorbital ophthalmic artery (OA) aneurysms. CASE DESCRIPTION: A 27-year-old man with no past medical history presented with 3 months of headaches. Imaging showed a large dysplastic left A1-2 junction aneurysm and a smaller saccular right A1-2 junction aneurysm, with potentially adherent domes. Two fusiform aneurysms of the intraorbital segment of the left OA were also identified. The patient underwent coil-assisted pipeline embolization of the left A1-A2 aneurysm, with complete obliteration and reconstitution of the normal parent vessel. The patient underwent coil embolization of the right A1-2 aneurysm 3 weeks later, which was found to have grown significantly at the time of treatment. Three-month follow-up showed spontaneous resolution of the OA aneurysms, persistent obliteration of the left aneurysm, and significant recurrence of the right aneurysm, which was treated with stent-assisted coil embolization. A second recurrence 3 months later was successfully treated with repeat coiling. At the time of this treatment, the patient was also found to have 2 de novo distal middle cerebral artery and ACA dysplastic aneurysms, which were not treated. Follow-up angiography 6 weeks later showed stable complete obliteration of the right A1-2 aneurysm and interval complete resolution of the dysplastic middle cerebral artery aneurysm. The distal ACA aneurysm was observed to have minimally increased in size; however, the parent vessel showed signs of interval partial thrombosis with contrast stasis within the aneurysm. This final aneurysm is being followed with serial imaging. The patient remains neurologically intact with complete resolution of his headaches. CONCLUSIONS: We report the case of a young man with no past medical history who presented with multiple dysplastic aneurysms. Successful staged endovascular intervention resulted in obliteration of aneurysms with spontaneous obliteration of the intraorbital OA aneurysms observed at 3 months. We present this case to review the multiple challenges of managing complex ACA aneurysms and to highlight the usefulness of endovascular intervention in their treatment.

Inflammatory mediators in vascular disease: identifying promising targets for intracranial aneurysm research.

Inflammatory processes are implicated in many diseases of the vasculature and have been shown to play a key role in the formation of intracranial aneurysms (IAs). Although the specific mechanisms underlying these processes have been thoroughly investigated in related pathologies, such as atherosclerosis, there remains a paucity of information regarding the immunopathology of IA. Cells such as macrophages and lymphocytes and their effector molecules have been suggested to be players in IA, but their specific interactions and the role of other components of the inflammatory response have yet to be determined. Drawing parallels between the pathogenesis of IA and other vascular disorders could provide a roadmap for developing a mechanistic understanding of the immunopathology of IA and uncovering useful targets for therapeutic intervention. Future research should address the presence and function of leukocyte subsets, mechanisms of leukocyte recruitment and activation, and the role of damage-associated molecular patterns in IA.

Single-center experience with a dual microcatheter technique for the endovascular treatment of wide-necked aneurysms.

OBJECT: The endovascular treatment of wide-necked aneurysms can be technically challenging due to distal coil migration or impingement of the parent vessel. In this paper, the authors illustrate an alternative method for the treatment of wide-necked intracranial aneurysms using a dual microcatheter technique. METHODS: The authors' first 100 consecutive patients who underwent coil embolization of a wide-necked aneurysm using a dual microcatheter technique are reported. With this technique, 2 microcatheters are used to introduce coils into the aneurysm. The coils are deployed either sequentially or concurrently to form a stable construct and prevent coil herniation or migration. Angiographic and clinical outcomes are reported. RESULTS: The technical success rate of the dual microcatheter technique is 91% with a morbidity and mortality of 1% and 2%, respectively. Clinical outcomes are excellent with 93% of patients demonstrating a modified Rankin Scale score of 0-2 at long-term follow-up regardless of their score at presentation. Retreatment rates are 18%. CONCLUSIONS: The dual microcatheter technique may be a safe and efficacious first line of treatment for widenecked aneurysms.

Therapeutic implications of estrogen for cerebral vasospasm and delayed cerebral ischemia induced by aneurysmal subarachnoid hemorrhage.

Cerebral vasospasm (CV) remains the leading cause of delayed morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). However, increasing evidence supports etiologies of delayed cerebral ischemia (DCI) other than CV. Estrogen, specifically 17 ß -estradiol (E2), has potential therapeutic implications for ameliorating the delayed neurological deterioration which follows aneurysmal SAH. We review the causes of CV and DCI and examine the evidence for E2-mediated vasodilation and neuroprotection. E2 potentiates vasodilation by activating endothelial nitric oxide synthase (eNOS), preventing increased inducible NOS (iNOS) activity caused by SAH, and decreasing endothelin-1 production. E2 provides neuroprotection by increasing thioredoxin expression, decreasing c-Jun N-terminal kinase activity, increasing neuroglobin levels, preventing SAH-induced suppression of the Akt signaling pathway, and upregulating the expression of adenosine A2a receptor. The net effect of E2 modulation of these various effectors is the promotion of neuronal survival, inhibition of apoptosis, and decreased oxidative damage and inflammation. E2 is a potentially potent therapeutic tool for improving outcomes related to post-SAH CV and DCI. However, clinical evidence supporting its benefits remains lacking. Given the promising preclinical data available, further studies utilizing E2 for the treatment of patients with ruptured intracranial aneurysms appear warranted.

External lumbar drain: A pragmatic test for prediction of shunt outcomes in idiopathic normal pressure hydrocephalus.

BACKGROUND: The consensus on most reliable supplemental test to predict the shunt responsiveness in patients with idiopathic normal pressure hydrocephalus (iNPH) is lacking. The aim of this study is to discuss the utility of external lumbar drain (ELD) in evaluation of shunt responsiveness for iNPH patients. METHODS: A retrospective review of 66 patients with iNPH was conducted. All patients underwent 4-day ELD trial. ELD-positive patients were offered ventriculoperitoneal shunt (VPS) surgery. The primary outcome evaluation parameters were gait and mini mental status examination (MMSE) assessment. The family and patient perception of improvement was accounted for in the outcome evaluation. RESULTS: There were 38 male and 28 female with mean age of 74 years (range 45-88 years). ELD trial was positive in 86% (57/66) of patients. No major complications were encountered with the ELD trial. A total of 60 patients (57 ELD-positive, 3 ELD-negative) underwent VPS insertion. The negative ELD trial (P = 0.006) was associated with poor outcomes following shunt insertion. The positive ELD trial predicted shunt responsiveness in 96% patients (P < 0.0001, OR = 96.2, CI = 11.6-795.3). A receiver operating characteristic (ROC) curve analysis revealed that the ELD trial is reasonably accurate in differentiating shunt responder from non-responder in iNPH patients (area under curve = 0.8 ± 0.14, P = 0.02, CI = 0.52-1.0). The mean follow-up period was 12-months (range 0.3-3 years). The significant overall improvement after VPS was seen in 92% (55/60). The improvement was sustained in 76% of patients at mean 3-year follow-up. The number of comorbid conditions (P = 0.034, OR = 4.15, CI = 1.2-9.04), and a history of cerebrovascular accident (CVA) (P = 0.035, OR = 4.4, CI = 1.9-14.6) were the predictors of poor outcome following shunt surgery. CONCLUSION: The positive ELD test predicted shunt responsiveness in 96% of patients. With adequate technique, maximal results with minimal complications can be anticipated. The number of comorbidities, history of CVA and negative ELD test were significantly associated with poor shunt outcomes.

Diagnosis and treatment of arterial dissections.

Dissections of the cervical and intracranial vessels represent an important source of stroke in those less than 50 years of age. This can occur spontaneously or following trauma, minor or major. Rapid diagnosis is essential to limit subsequent sequelae and modern computed tomographic angiography represents an appropriately sensitive modality. Treatment must be individualized to the patient and can consist of an antiplatelet regimen, anticoagulation, or endovascular intervention. No evidence demonstrates superiority of either medical modality and even aspirin alone may be efficacious. Consideration should be given to this in the multi-trauma population in which more aggressive anticoagulation is contraindicated. In addition, thrombolytic administration should not be withheld would it otherwise be indicated. Endovascular intervention is reserved for those with hemodynamically significant narrowing, enlarging pseudoaneurysms, fistulas formation, or subarachnoid hemorrhage.

Intraoperative ultrasound guidance for the placement of permanent ventricular cerebrospinal fluid shunt catheters: a single-center historical cohort study.

OBJECTIVE: Despite the frequency with which ventriculoperitoneal shunts are placed, ventricular catheter revision rates remains as high as 30%-40% at 1 year. Many neurosurgeons place ventricular catheters "blindly" depending on anatomical landmarks and personal experience. To determine whether intraoperative ultrasonography is beneficial for ventricular catheter placement, we performed a historical cohort study comparing shunts placed with intraoperative ultrasound (US) guidance to those placed blindly. METHODS: We reviewed all shunts placed by the Department of Neurosurgery at the University of Virginia from January 2005 to January 2007. During that time 211 patients underwent 242 shunts, with US use determined by surgeon's preference. Ninety-two shunts were placed by the use of US guidance, and 150 were placed without US. Adults received 176 shunts, 56 with US. Children received 66 shunts, 36 with US. Mean follow-up was 21.6 months. The primary end points examined were shunt revision, ventricular catheter revision (VCR), and acute VCR (revision within 1 week for an improperly-placed catheter). RESULTS: The use of US was associated with a statistically significant decrease in shunt revisions (odds ratio 0.492; 95% confidence interval 0.253-0.958). Of the shunts placed with US guidance, 21.7% required revision, compared with 29.3% without US. VCRs and acute VCRs occurred in 9.8% and 2.2%, respectively, for US shunts, compared with 14% and 5.3% without US. Pediatric revision rates were 30.6% with US versus 53.3% without, whereas adult rates were 16.1% and 23.3%, respectively. The benefit of US was more profound for occipital shunts. CONCLUSIONS: The use of US for the placement of permanent cerebrospinal fluid shunt catheters is associated with a decreased risk of shunt revision.

Multi-institutional neurosurgical training initiative at a tertiary referral center in Mwanza, Tanzania: where we are after 2 years.

BACKGROUND: The paucity of neurosurgical care in East Africa remains largely unaddressed. A sustained investment in local health infrastructures and staff training is needed to create an independent surgical capacity. The Madaktari organization has addressed this issue by starting initiatives to train local general surgeons and assistant medical officers in basic neurosurgical procedures. We report illustrative cases since beginning of the program in Mwanza in 2009 and focus on the most recent training period. METHODS: A multi-institutional neurosurgical training program and a surgical database was created at a tertiary referral center in Mwanza, Tanzania. We collected clinical data on consecutive patients who underwent a neurosurgical procedure between September 9th and December 1st, 2011. All procedures were performed by a local surgeon under the supervision of a visiting neurosurgeon. Since the inception of the training initiative, comprehensive multidisciplinary training courses in Tanzania and an annual visiting fellowship for East African surgeons to travel to a major U.S. medical center have been established. RESULTS: At initial visits infrastructure and feasibility of complex case scenarios was assessed. Surgeries for brain tumors and complex spinal cases were performed. During the 3-month training period, 62 patients underwent surgery. Pediatric hydrocephalus comprised 52% of patients, 11% suffered from meningomyelocelia, and 6% presented with an encephalocele. A total of 24% of patients were treated for trauma-related conditions, representing 75% of the adult patients. A total of 10% of patients had surgery because of traumatic spine injury, and 15% of operations were on patients with severe head injury. A total of 6% of patients presented with degenerative spine disease. One patient sustained a fatal perioperative complication. At the end of the training period, the local general surgeon was able to perform all basic neurosurgical cases independently. CONCLUSIONS: Neurosurgical care in Tanzania needs to address a diverse, unique disease burden. We found that local surgeons could be enabled to safely perform basic cranial and spinal neurosurgical procedures through immersive, 1-on-1 on-site collaborations, multidisciplinary courses, and educational visiting fellowships.

Tumor necrosis factor-α modulates cerebral aneurysm formation and rupture.

Inflammation is a critical process behind cerebral aneurysm formation and rupture. Tumor necrosis factor alpha (TNF-α) is a key immune modulator that has been implicated in cerebral aneurysm pathophysiology. This may occur through TNF-α-mediated endothelial injury, smooth muscle cell phenotypic modulation, recruitment of macrophages, activation of chemotactic cytokines, upregulation of matrix remodeling genes, production of free radicals leading to oxidative stress, and ultimately cellular apoptosis. Recent studies have indicated that TNF-α may be a potential target for the development of novel medical therapies, but additional experimental data is needed to clarify the intricacies of TNF-α activation and its critical downstream targets in cerebral aneurysms. This review provides an update on the mechanisms underlying TNF-α-induced molecular modulation in cerebral aneurysms.

Vascular smooth muscle cells in cerebral aneurysm pathogenesis.

Vascular smooth muscle cells (SMC) maintain significant plasticity. Following environmental stimulation, SMC can alter their phenotype from one primarily concerned with contraction to a pro-inflammatory and matrix remodeling phenotype. This is a critical process behind peripheral vascular disease and atherosclerosis, a key element of cerebral aneurysm pathology. Evolving evidence demonstrates that SMCs and phenotypic modulation play a significant role in cerebral aneurysm formation and rupture. Pharmacological alteration of smooth muscle cell function and phenotypic modulation could provide a promising medical therapy to inhibit cerebral aneurysm progression. This study reviews vascular SMC function and its contribution to cerebral aneurysm pathophysiology.

Safety and pharmacokinetics of sodium nitrite in patients with subarachnoid hemorrhage: a phase IIa study.

OBJECT: Intravenous sodium nitrite has been shown to prevent and reverse cerebral vasospasm in a primate model of subarachnoid hemorrhage (SAH). The present Phase IIA dose-escalation study of sodium nitrite was conducted to determine the compound's safety in humans with aneurysmal SAH and to establish its pharmacokinetics during a 14-day infusion. Methods In 18 patients (3 cohorts of 6 patients each) with SAH from a ruptured cerebral aneurysm, nitrite (3 patients) or saline (3 patients) was infused. Sodium nitrite and saline were delivered intravenously for 14 days, and a dose-escalation scheme was used for the nitrite, with a maximum dose of 64 nmol/kg/min. Sodium nitrite blood levels were frequently sampled and measured using mass spectroscopy, and blood methemoglobin levels were continuously monitored using a pulse oximeter. RESULTS: In the 14-day infusions in critically ill patients with SAH, there was no toxicity or systemic hypotension, and blood methemoglobin levels remained at 3.3% or less in all patients. Nitrite levels increased rapidly during intravenous infusion and reached steady-state levels by 12 hours after the start of infusion on Day 1. The nitrite plasma half-life was less than 1 hour across all dose levels evaluated after stopping nitrite infusions on Day 14. CONCLUSIONS: Previous preclinical investigations of sodium nitrite for the prevention and reversal of vasospasm in a primate model of SAH were effective using doses similar to the highest dose examined in the current study (64 nmol/kg/min). Results of the current study suggest that safe and potentially therapeutic levels of nitrite can be achieved and sustained in critically ill patients after SAH from a ruptured cerebral aneurysm.

Minimally invasive treatment of intracerebral hemorrhage with magnetic resonance-guided focused ultrasound.

OBJECT: Intracerebral hemorrhage (ICH) is a major cause of death and disability throughout the world. Surgical techniques are limited by their invasive nature and the associated disability caused during clot removal. Preliminary data have shown promise for the feasibility of transcranial MR-guided focused ultrasound (MRgFUS) sonothrombolysis in liquefying the clotted blood in ICH and thereby facilitating minimally invasive evacuation of the clot via a twist-drill craniostomy and aspiration tube. METHODS AND RESULTS: In an in vitro model, the following optimum transcranial sonothrombolysis parameters were determined: transducer center frequency 230 kHz, power 3950 W, pulse repetition rate 1 kHz, duty cycle 10%, and sonication duration 30 seconds. Safety studies were performed in swine (n = 20). In a swine model of ICH, MRgFUS sonothrombolysis of 4 ml ICH was performed. Magnetic resonance imaging and histological examination demonstrated complete lysis of the ICH without additional brain injury, blood-brain barrier breakdown, or thermal necrosis due to sonothrombolysis. A novel cadaveric model of ICH was developed with 40-ml clots implanted into fresh cadaveric brains (n = 10). Intracerebral hemorrhages were successfully liquefied (> 95%) with transcranial MRgFUS in a highly accurate fashion, permitting minimally invasive aspiration of the lysate under MRI guidance. CONCLUSIONS: The feasibility of transcranial MRgFUS sonothrombolysis was demonstrated in in vitro and cadaveric models of ICH. Initial in vivo safety data in a swine model of ICH suggest the process to be safe. Minimally invasive treatment of ICH with MRgFUS warrants evaluation in the setting of a clinical trial.

Transcranial magnetic resonance-guided focused ultrasound surgery for trigeminal neuralgia: a cadaveric and laboratory feasibility study.

OBJECT: Transcranial MR-guided focused ultrasound surgery (MRgFUS) is evolving as a treatment modality in neurosurgery. Until now, the trigeminal nerve was believed to be beyond the treatment envelope of existing high-frequency transcranial MRgFUS systems. In this study, the authors explore the feasibility of targeting the trigeminal nerve in a cadaveric model with temperature assessments using computer simulations and an in vitro skull phantom model fitted with thermocouples. METHODS: Six trigeminal nerves from 4 unpreserved cadavers were targeted in the first experiment. Preprocedural CT scanning of the head was performed to allow for a skull correction algorithm. Three-Tesla, volumetric, FIESTA MRI sequences were performed to delineate the trigeminal nerve and any vascular structures of the cisternal segment. The cadaver was positioned in a focused ultrasound transducer (650-kHz system, ExAblate Neuro, InSightec) so that the focus of the transducer was centered at the proximal trigeminal nerve, allowing for targeting of the root entry zone (REZ) and the cisternal segment. Real-time, 2D thermometry was performed during the 10- to 30-second sonication procedures. Post hoc MR thermometry was performed on a computer workstation at the conclusion of the procedure to analyze temperature effects at neuroanatomical areas of interest. Finally, the region of the trigeminal nerve was targeted in a gel phantom encased within a human cranium, and temperature changes in regions of interest in the skull base were measured using thermocouples. RESULTS: The trigeminal nerves were clearly identified in all cadavers for accurate targeting. Sequential sonications of 25-1500 W for 10-30 seconds were successfully performed along the length of the trigeminal nerve starting at the REZ. Real-time MR thermometry confirmed the temperature increase as a narrow focus of heating by a mean of 10°C. Postprocedural thermometry calculations and thermocouple experiments in a phantom skull were performed and confirmed minimal heating of adjacent structures including the skull base, cranial nerves, and cerebral vessels. For targeting, inclusion of no-pass regions through the petrous bone decreased collateral heating in the internal acoustic canal from 16.7°C without blocking to 5.7°C with blocking. Temperature at the REZ target decreased by 3.7°C with blocking. Similarly, for midcisternal targeting, collateral heating at the internal acoustic canal was improved from a 16.3°C increase to a 4.9°C increase. Blocking decreased the target temperature increase by 4.4°C for the same power settings. CONCLUSIONS: This study demonstrates focal heating of up to 18°C in a cadaveric trigeminal nerve at the REZ and along the cisternal segment with transcranial MRgFUS. Significant heating of the skull base and surrounding neural structures did not occur with implementation of no-pass regions. However, in vivo studies are necessary to confirm the safety and efficacy of this potentially new, noninvasive treatment.

Potential intracranial applications of magnetic resonance-guided focused ultrasound surgery.

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) has the potential to create a shift in the treatment paradigm of several intracranial disorders. High-resolution MRI guidance combined with an accurate method of delivering high doses of transcranial ultrasound energy to a discrete focal point has led to the exploration of noninvasive treatments for diseases traditionally treated by invasive surgical procedures. In this review, the authors examine the current intracranial applications under investigation and explore other potential uses for MRgFUS in the intracranial space based on their initial cadaveric studies.

Magnetic resonance-guided focused ultrasound surgery: Part 2: A review of current and future applications.

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) is a novel combination of technologies that is actively being realized as a noninvasive therapeutic tool for a myriad of conditions. These applications are reviewed with a focus on neurological use. A combined search of PubMed and MEDLINE was performed to identify the key events and current status of MRgFUS, with a focus on neurological applications. MRgFUS signifies a potentially ideal device for the treatment of neurological diseases. As it is nearly real time, it allows monitored provision of treatment location and energy deposition; is noninvasive, thereby limiting or eliminating disruption of normal tissue; provides focal delivery of therapeutic agents; enhances radiation delivery; and permits modulation of neural function. Multiple clinical applications are currently in clinical use and many more are under active preclinical investigation. The therapeutic potential of MRgFUS is expanding rapidly. Although clinically in its infancy, preclinical and early-phase I clinical trials in neurosurgery suggest a promising future for MRgFUS. Further investigation is necessary to define its true potential and impact.

Catheter-tip mass mimicking a spinal epidural hematoma.

As > 95,000 spinal drug-delivery devices have been implanted since their inception in the 1980s, the recognition of associated adverse effects is essential. Since 1985, numerous reports have described the presence of catheter-tip granulomas. In the current case, the authors describe a less frequent complication of epidural bupivacaine precipitation. Regardless of origin, these unusual lesions have been increasingly recognized as a rare but potentially devastating complication of intrathecal infusions. A 34-year-old woman with an intrathecal pain-pump delivering fentanyl, bupivacaine, and clonidine for thoracic outlet syndrome presented with rapidly progressive neurological deficits and increasing neck and upper-extremity pain. Neuroimaging disclosed a C7-T1 mass that was thought to be a hematoma that occurred after a recent epidural steroid injection. On emergency surgical decompression by laminectomy, a chalky mass containing viscous fluid was identified surrounding an epidurally located catheter. Histopathological examination revealed a proteinaceous mass consistent with drug precipitate enveloped by fibrosis and mild inflammation. Postoperatively, the patient recovered with minimal neurological deficit. The presentation and clinical relevance are discussed in conjunction with a review of the pertinent literature. Catheter-tip masses are a rare complication of implantable drug-delivery devices occurring in < 3% of all patients with intrathecal catheters. Regardless of the anatomical site, the most common presenting features are neurological deficits, worsening pain, and increasing requirements for pain medication. Expedient diagnosis and management are essential for physicians treating patients with spinal infusion devices to prevent significant neurological sequelae. Further investigation is warranted regarding the use of bupivacaine as an adjunct in permanent spinal infusion systems.