Bradley A. Gross

The natural history of intracranial cavernous malformations

Literature reports on the natural history of cerebral cavernous malformations (CMs) are numerous, with considerable variability in lesion epidemiology, hemorrhage rates, and risk factors for hemorrhage. In this review, the authors performed a meta-analysis of 11 natural history studies. The overall male-to-female ratio was 1:1, and the mean age at presentation was 30.6 years. Overall, 37% of patients presented with seizures, 36% with hemorrhage, 23% with headaches, 22% with focal neurological deficits, and 10% were asymptomatic. Some patients had more than one symptom. Seizure presentation was most prevalent among supratentorial CMs, while focal neurological deficits were common in patients with infratentorial CMs. By location, CMs were in the cerebral hemispheres (66%), brainstem (18%), basal ganglia or thalamus (8%), cerebellum (6%), and other (2.5% [combined supra- and infratentorial, callosal or insular]). Overall, 19% of patients harbored multiple intracranial CMs, and 9% had radiographically apparent associated developmental venous anomalies. An overall annual hemorrhage rate of 2.4% per patient-year (range 1.6%-3.1%) was identified across 3 studies. Prior hemorrhage and female sex were risk factors for bleeding, while CM size and multiplicity did not affect hemorrhage rates. Although not impacting the hemorrhage rate itself, deep location was a risk factor for increased clinical aggressiveness.

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 ones 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.

Differences in simple morphological variables in ruptured and unruptured middle cerebral artery aneurysms

OBJECTnManagement of unruptured intracranial aneurysms remains controversial in neurosurgery. The contribution of morphological parameters has not been included in the treatment paradigm in a systematic manner or for any particular aneurysm location. The authors present a large sample of middle cerebral artery (MCA) aneurysms that were assessed using morphological variables to determine the parameters associated with aneurysm rupture.nnnMETHODSnPreoperative CT angiography (CTA) studies were evaluated using Slicer software to generate 3D models of the aneurysms and their surrounding vascular architecture. Morphological parameters examined in each model included 5 variables already defined in the literature (aneurysm size, aspect ratio, aneurysm angle, vessel angle, and size ratio) and 3 novel variables (flow angle, distance to the genu, and parent-daughter angle). Univariate and multivariate statistical analyses were performed to determine statistical significance.nnnRESULTSnBetween 2005 and 2008, 132 MCA aneurysms were treated at a single institution, and CTA studies of 79 aneurysms (40 ruptured and 39 unruptured) were analyzed. Fifty-three aneurysms were excluded because of reoperation (4), associated AVM (2), or lack of preoperative CTA studies (47). Ruptured aneurysms were associated with larger size, greater aspect ratio, larger aneurysm and flow angles, and smaller parent-daughter angle. Multivariate logistic regression revealed that aspect ratio, flow angle, and parent-daughter angle were the strongest factors associated with ruptured aneurysms.nnnCONCLUSIONSnAspect ratio, flow angle, and parent-daughter angle are more strongly associated with ruptured MCA aneurysms than size. The association of parameters independent of aneurysm morphology with ruptured aneurysms suggests that these parameters may be associated with an increased risk of aneurysm rupture. These factors are readily applied in clinical practice and should be considered in addition to aneurysm size when assessing the risk of aneurysm rupture specific to the MCA location.

Intramedullary spinal cord cavernous malformations

Although originally the subject of rare case reports, intramedullary spinal cord cavernous malformations (CMs) have recently surfaced in an increasing number of case series and natural history reports in the literature. The authors reviewed 27 publications with 352 patients to consolidate modern epidemiological, natural history, and clinical and surgical data to facilitate decision making when managing these challenging vascular malformations. The mean age at presentation was 42 years without a sex predilection. Thirty-eight percent of the cases were cervical, 57% thoracic, 4% lumbar, and 1% unspecified location. Nine percent of the patients had a family history of CNS CMs. Twenty-seven percent of the patients had an associated cranial CM. On presentation 63% of the patients had motor deficits, 65% had sensory deficits, 27% had pain, and 11% had bowel or bladder dysfunction. Presentation was acute in 30%, recurrent in 16%, and progressive in 54% of cases. An overall annual hemorrhage rate was calculated as 2.5% for 92 patients followed up for a total of 2571 patient-years. Across 24 reviewed surgical series, a 91% complete resection rate was found. Transient morbidity was seen in 36% of cases. Sixty-one percent of patients improved, 27% were unchanged, and 12% were worse at the long-term follow-up. Using this information, the authors review surgical nuances in treating these lesions and propose a management algorithm.

The impact of aspirin and anticoagulant usage on outcomes after aneurysmal subarachnoid hemorrhage: a Nationwide Inpatient Sample analysis.

OBJECTIVE Although aspirin usage may be associated with a decreased risk of rupture of cerebral aneurysms, any potential therapeutic benefit from aspirin must be weighed against the theoretical risk of greater hemorrhage volume if subarachnoid hemorrhage (SAH) occurs. However, few studies have evaluated the association between prehemorrhage aspirin use and outcomes. This is the first nationwide analysis to evaluate the impact of long-term aspirin and anticoagulant use on outcomes after SAH. METHODS Data from the Nationwide Inpatient Sample (NIS; 2006-2011) were extracted. Patients with a primary diagnosis of SAH who underwent microsurgical or endovascular aneurysm repair were included; those with a diagnosis of an arteriovenous malformation were excluded. Multivariable logistic regression was performed to calculate the adjusted odds of in-hospital mortality, a nonroutine discharge (any discharge other than to home), or a poor outcome (death, discharge to institutional care, tracheostomy, or gastrostomy) for patients with long-term aspirin or anticoagulant use. Multivariable linear regression was used to evaluate length of hospital stay. Covariates included patient age, sex, comorbidities, primary payer, NIS-SAH severity scale, intracerebral hemorrhage, cerebral edema, herniation, modality of aneurysm repair, hospital bed size, and whether the hospital was a teaching hospital. Subgroup analyses exclusively evaluated patients treated surgically or endovascularly. RESULTS The study examined 11,549 hospital admissions. Both aspirin (2.1%, n = 245) and anticoagulant users (0.9%, n = 108) were significantly older and had a greater burden of comorbid disease (p < 0.001); severity of SAH was slightly lower in those with long-term aspirin use (p = 0.03). Neither in-hospital mortality (13.5% vs 12.6%) nor total complication rates (79.6% vs 80.0%) differed significantly by long-term aspirin use. Additionally, aspirin use was associated with decreased odds of a cardiac complication (OR 0.57, 95% CI 0.36%-0.91%, p = 0.02) or of venous thromboembolic events (OR 0.53, 95% CI 0.30%-0.94%, p = 0.03). Length of stay was significantly shorter (15 days vs 17 days [12.73%], 95% CI 5.22%-20.24%, p = 0.001), and the odds of a nonroutine discharge were lower (OR 0.63, 95% CI 0.48%-0.83%, p = 0.001) for aspirin users. In subgroup analyses, the benefits of aspirin were primarily noted in patients who underwent coil embolization; likewise, among patients treated endovascularly, the adjusted odds of a poor outcome were lower among long-term aspirin users (31.8% vs 37.4%, OR 0.63, 95% CI 0.42%-0.94%, p = 0.03). Although the crude rates of in-hospital mortality (19.4% vs 12.6%) and poor outcome (53.6% vs 37.6%) were higher for long-term anticoagulant users, in multivariable logistic regression models these variations were not significantly different (mortality: OR 1.36, 95% CI 0.89%-2.07%, p = 0.16; poor outcome: OR 1.09, 95% CI 0.69%-1.73%, p = 0.72). CONCLUSIONS In this nationwide study, neither long-term aspirin nor anticoagulant use were associated with differential mortality or complication rates after SAH. Aspirin use was associated with a shorter hospital stay and lower rates of nonroutine discharge, with these benefits primarily observed in patients treated endovascularly.

Intracranial Aneurysms in the Youngest Patients: Characteristics and Treatment Challenges

Background: Characteristics and treatment challenges of aneurysms in young children differ from those in older pediatric patients. Methods: Records of children undergoing cerebral or spinal angiography by the senior neurointerventionalist (D.B.O.) from October 2006 to January 2014 were reviewed to identify patients with digital subtraction angiography-confirmed intracranial aneurysms. Demographics, presentation, subtype of aneurysm, treatment strategy, and outcome were evaluated. Results: Of 763 pediatric cases, 33 were of children harboring cerebral aneurysms. Overall, 48% were male, 24% presented with hemorrhage and 67% harbored fusiform/dissecting aneurysms. Patients aged 0-10 years were significantly more likely to harbor nonsaccular, dissecting/fusiform aneurysms (84 vs. 43%, p = 0.02). A total of 13/22 pediatric patients harboring dissecting/fusiform aneurysms were male (59%) compared to 3/11 with saccular aneurysms (27%, p = 0.14). Overall, 15 patients underwent endovascular treatment (45%) and 8 underwent microsurgical treatment (24%). There was no significant difference in treatment approach based on patient age or aneurysm morphology. Overall, 19/23 aneurysms were occluded after initial treatment (83%); there were 2 procedure-related complications with neurological sequelae (9%). Conclusion: We demonstrate that the youngest patients (10 years and under) have aneurysms even more distinct and less similar to adult aneurysms than those in the larger pediatric cohort.

Addressing challenges in 4 F and 5 F arterial access for neurointerventional procedures in infants and young children

Background Among the technical challenges involved in safely performing neuroendovascular procedures in infants are limitations on the size of femoral arterial access catheters. Restricting groin access to 4 F and 5 F systems constrains the range of procedures that can potentially be performed. Methods and Results We present here a consecutive series of transfemoral angiographic procedures in children with no permanent and one transient case of groin morbidity related to femoral access. We illustrate two strategies for using 4 F and 5 F systems for interventions in a manner that enables such techniques as balloon assisted coil embolization and the deployment of triaxial catheter systems to be used. Conclusions Extremely low groin morbidity is achievable using rigorous parameters around femoral catheterization in children. With creative approaches to working within the limitations of the access vessel size, complex endovascular neurointerventions are possible, even in the youngest infants.

Pituitary Dysfunction After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis.

BACKGROUNDnThe prevalence of hypothalamic-pituitary dysfunction after aneurysmal subarachnoid hemorrhage has not been precisely determined, and conflicting results have been reported in the literature.nnnOBJECTIVEnTo perform a systematic review and meta-analysis investigating the prevalence of pituitary insufficiency after aneurysmal subarachnoid hemorrhage and to focus on basal serum and dynamic test differences.nnnMETHODSnThe prevalence of pituitary dysfunction was quantified at 3 to 6 months and >6 months after aneurysmal subarachnoid hemorrhage. Proportions were transformed with the logit transformation. A subgroup analysis was performed focusing on the differences in outcome between basal serum and dynamic tests for the diagnosis of growth hormone deficiency (GHD) and secondary adrenal insufficiency.nnnRESULTSnOverall prevalence of hypopituitarism differed considerably between studies, ranging from 0.05 to 0.45 in studies performed between 3 and 6 months after the event and from 0 to 0.55 in long-term studies (>6 months), with pooled frequencies of 0.31 (95% confidence interval [CI]: 0.22-0.43) and 0.25 (95% CI: 0.16-0.36), respectively. Pooled frequency of GHD at 3 to 6 months was 0.14 (95% CI: 0.08-0.24). At >6 months, GHD prevalence was 0.19 (95% CI: 0.13-0.26) overall, but ranged from 0.15 (95% CI: 0.06-0.33) with the insulin tolerance test to 0.25 (95% CI: 0.15-0.36) using the growth hormone releasing hormone + arginine test.nnnCONCLUSIONnHypopituitarism is a common complication in patients with aneurysmal subarachnoid hemorrhage, with GHD being the most prevalent diagnosis. We showed that variations in prevalence rates in the literature are partly due to methodological differences among pituitary function tests.nnnABBREVIATIONSnACTH, adrenocorticotropic hormoneaSAH, aneurysmal subarachnoid hemorrhageGHD, growth hormone deficiencyGHRH, growth hormone-releasing hormoneGST, glucagon stimulation testIGF, insulin-like growth factor 1ITT, insulin tolerance testSAH, subarachnoid hemorrhage.

Time to re-assess the treatment of idiopathic intracranial hypertension

Patients with idiopathic intracranial hypertension (IIH) have debilitating headaches and, in severe cases, life-altering papilledema and visual loss.1 The time-honored approach of cerebrospinal fluid (CSF) diversion for medically refractory IIH is often complicated by patient body habitus and a small ventricular system.2 ,3 The majority of patients with IIH have demonstrable venous sinus stenosis, potentially producing intracranial hypertension as a result of impaired CSF absorption.4 ,5nnPreliminary evidence suggests that venous sinus stenting (VSS) may be beneficial.3 ,6 Our own experience shows symptomatic improvement in 70% of patients after stenting with a high rate of stent patency and a low incidence of neurological complications.7 In addition, a follow-up study, a mean of 3u2005years after treatment, found continued patency and normal drainage of the vein of Labbe in all cases in which it had been covered by a stent.8nnRecently, Satti et al 3 performed a unique meta-analysis of interventional/surgical procedures performed for the treatment of medically refractory IIH. Results illustrated comparable or superior results for both headache and visual symptoms after VSS in comparison with optic nerve sheath fenestration and CSF diversion. The authors found 18 clinical studies with 712 …

Cerebrovascular neurosurgery in 2012.

Considerable advances in our understanding of the natural history and treatment of cerebrovascular disease were made in 2012. The landmark Unruptured Cerebral Aneurysm Study in Japan was published, illustrating a significantly greater rupture risk than previously reported for small anterior and posterior communicating artery aneurysms, those with daughter domes, and giant aneurysms. Results from the Cerecyte (DePuy Synthes, West Chester, PN, USA) coil trial did not demonstrate a statistically significant positive impact of these bioactive coils on angiographic occlusion rates or outcome. The Clazosentan to Overcome Neurological Ischemia and Infarct Occurring after Subarachnoid Hemorrhage study was also published and unfortunately did not demonstrate an overall favorable long-term functional outcome rate for patients with aneurysmal subarachnoid hemorrhage receiving clazosentan. Studies furthering our understanding of the natural history and treatment of vascular malformations were also published, including large prospective natural history studies of cavernous malformations from the Mayo Clinic and the Scottish Audit of Intracranial Vascular Malformations database. Although pregnancy was found to be a significant risk factor for arteriovenous malformation hemorrhage, several studies did not demonstrate pregnancy as a significant risk factor for cavernous malformation hemorrhage. Finally, prospective randomized control trials illustrated significantly improved angiographic and clinical outcome results for both the Solitaire (ev3 Endovascular, Plymouth, MN, USA; SWIFT trial) and Trevo (Concentric Medical, Mountainview, CA, USA; TREVO 2 trial) stent retrievers as compared to the Merci (Concentric Medical) clot retriever.