Liu KC, Starke RM, Durst CR, et al. Venous sinus stenting for reduction of intracranial pressure in IIH: a prospective pilot study. J Neurosurg. 2017;127(5):1126-1133. doi:10.3171/2016.8.JNS16879.
Although many cases of IIH are idiopathic, a number of patients have been found to have venous sinus stenosis as a potential underlying mechanism. During cerebral venography, manometry has demonstrated significant pressure gradients across the stenotic segments with elevated venous pressures most frequently proximally in the superior sagittal sinus. Currently, it is unclear whether this stenosis is the cause of IIH or the result of elevated ICP as a secondary disease process. Although stenting of the venous sinus stenosis has been shown in select cases to resolve the pressure gradient, the effect on ICP remains unclear. Additionally, the effects on visual and neurological outcomes remain incompletely defined.
The purpose of this pilot study was to assess the effects of venous sinus stenting on ICP in a small group of patients with IIH.
Ten patients for whom medical therapy had failed were prospectively followed. Ophthalmological examinations were assessed, and patients with venous sinus stenosis on MR angiography proceeded to catheter angiography, venography with assessment of pressure gradient, and ICP monitoring. Patients with elevated ICP measurements and an elevated pressure gradient across the stenosis were treated with stent placement.
All patients had elevated venous pressure (mean 39.5 mm Hg), an elevated gradient across the venous sinus stenosis (30.0 mm Hg), and elevated ICP (42.2 mm Hg). Following stent placement, all patients had resolution of the stenosis and gradient (1 mm Hg). The ICP values showed an immediate decrease (to a mean of 17.0 mm Hg), and further decreased overnight (to a mean of 8 mm Hg). All patients had subjective and objective improvement, and all but one improved during follow-up.
The novel findings of this study are that in patients with IIH, elevated ICP, and venous stenosis with an elevated pressure gradient, venous sinus stenting resulted in 1) immediate resolution of the venous pressure gradient across the stenosis; 2) significant decrease in ICP values to the normal range; 3) improvements in functional outcomes and neurological examinations; and 4) improvements in ophthalmological examination findings. Specifically, patients presenting with papilledema had resolution as demonstrated on funduscopic imaging and OCT and improvement on visual field testing, and patients presenting with optic atrophy had optic nerve thinning on follow-up optical coherence tomography (OCT), but improvement in visual field testing.
They conclude that for selected patients with IIH and venous sinus stenosis with an elevated pressure gradient and elevated ICP, venous sinus stenting results in resolution of the venous pressure gradient, reduction in ICP, and functional, neurological, and ophthalmological improvement. As patients are at risk for stent-adjacent stenosis, further follow-up is necessary to determine long-term outcomes.
5 figures, 2 Tables
Mokin M, Primiani CT, Ren Z, et al. Endovascular Treatment of Middle Cerebral Artery M2 Occlusion Strokes: Clinical and Procedural Predictors of Outcomes. Neurosurgery. 2017;81(5):795-802. doi:10.1093/neuros/nyx060.
American Heart Association 2015 guidelines recommend stent retriever thrombectomy for patients with acute occlusion of the internal carotid artery (ICA) or the middle cerebral artery (MCA) M1 segment (class I; level of evidence A). The number of patients with isolated occlusion of more distal MCA branches included in those trials was small, as the trials were not designed to evaluate the safety and efficacy of thrombectomy for more distal lesions, such as MCA M2 occlusions. Furthermore, there are no randomized trials that have specifically evaluated the benefits of thrombectomy in the setting of distal MCA occlusions as a primary outcome measure. These facts are reflected in the AHA guidelines, which state distal MCA thrombectomy is reasonable but of uncertain benefit when initiated within the first 6 h of symptom onset (class IIb; level of evidence C).
The authors performed a multicenter retrospective analysis of consecutive patients with acute MCA M2 segment occlusion who underwent thrombectomy with stent retrievers or primary aspiration thrombectomy (including A Direct Aspiration First Pass Technique approach). They correlated clinical and radiographic outcomes with demographic, clinical, and technical characteristics.
One hundred and seventeen patients were included in analysis (median admission National Institutes of Health stroke scale [NIHSS] score 15, mean age 67.0, 42% females). Good clinical outcome at 3 months (modified Rankin scale [mRS] ≤ 2) was achieved in 56% of patients. Treatment beyond 6 h of symptoms onset and age over 80 were not predictive of poor outcome. NIHSS > 15 was a strong predictor of clinical outcome, based on mRS distribution at 3 months. Direct aspiration and primary stent retriever thrombectomy approaches showed similar radiographic and clinical success rates.
In this multicenter retrospective study of patients who underwent mechanical thrombectomy for isolated acute M2 occlusions with moderate–severe stroke severities, 56% of patients achieved a good clinical outcome at 3 months with a low rate of periprocedural complications. Good outcomes in this study are comparable to the outcomes observed in the endovascular arm of the ESCAPE and SWIFT PRIME trials (53% and 60%, respectively). The high rates of successful recanalization (85%), good clinical outcomes (56%), and low complication rate further support the role of mechanical thrombectomy in patients presenting with symptomatic acute M2 segment occlusions.
They conclude that advanced age and time to treatment beyond 6 h from symptom onset were not predictive of clinical outcome with thrombectomy. NIHSS score above 15 was a strong predictor of outcome. Direct aspiration and primary stent retriever thrombectomy showed similar efficacy.
6 Tables
Nurmonen HJ, Huttunen T, Huttunen J, et al. Polycystic kidney disease among 4,436 intracranial aneurysm patients from a defined population. Neurology. 2017;89(18):1852-1859. doi:10.1212/WNL.0000000000004597.
Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disease with a prevalence of 1:400–1,000 live births. It is caused by mutations in either PKD1 (85%) or PKD2 (15%). Together they are essential to vascular wall integrity and shear stress endurance. The main feature of ADPKD is formation of cysts in the tubular epithelium of the nephron, resulting in loss of functional renal tissue, enlargement of the kidneys, and terminal uremia. Symptoms of ADPKD include hypertension, back pain, hematuria, and infections of the urinary tract and singular cysts. Extrarenal manifestations of the disease include intracranial aneurysms (IAs).
The authors fused data from the Kuopio Intracranial Aneurysm database (n= 4,436 IA patients) and Finnish nationwide registries into a population-based series of 53 IA patients with ADPKD to compare the aneurysm- and patient-specific characteristics of IA disease in ADPKD and in the general IA population, and to identify risks for de novo IA formation.
There were 33 patients with ADPKD with aSAH and 20 patients with ADPKD with unruptured IAs. The median size of ruptured IAs in ADPKD was significantly smaller than in the general population (6.00 vs 8.00 mm) and the proportion of small ruptured IAs was significantly higher (31%vs 18%). Median age at aSAH was 42.8 years, 10 years younger than in the general IA population. Multiple IAs were present in 45% of patients with ADPKD compared to 28% in the general IA population. Cumulative risk of de novo IA formation was 1.3% per patient-year (vs 0.2% in the general IA population). Hazard for de novo aneurysm formation was significantly elevated in patients with ADPKD.
They conclude that subarachnoid hemorrhage occurs at younger age and from smaller IAs in patients with ADPKD and risk for de novo IAs is higher than in the general Eastern Finnish population. ADPKD should be considered as an indicator for long-term angiographic follow-up in patients with diagnosed IAs (CTA, MRA, DSA).
2 Figures, 3 Tables
Jain A, Hassanzadeh H, Puvanesarajah V, et al. Incidence of perioperative medical complications and mortality among elderly patients undergoing surgery for spinal deformity: analysis of 3519 patients. J Neurosurg Spine. 2017;27(5):534-539. doi:10.3171/2017.3.SPINE161011.
High perioperative complication rates have been reported in elderly patients (aged 65 years or older) surgically treated for adult spinal deformity and range from 37% to 71%. A large proportion of the morbidity in the elderly is caused by serious medical complications such as myocardial infarction (MI) and cerebrovascular accidents (CVAs), which become more prevalent with older age. Despite high complication rates, several studies have found that elderly patients may achieve equal or greater improvements in self-reported outcomes compared with younger patients (aged 64 years or younger). However, no study has comprehensively assessed the rates of major medical complications among elderly patients surgically treated for adult spinal deformity (ASD). The authors queried a multicenter, prospective, surgeon-maintained database (SMD) to identify patients 65 years or older who underwent surgical correction of ASD from 2008 through 2014 and had a minimum 2 years of follow-up (n = 153). They also queried a Centers for Medicare & Medicaid Services claims database (MCD) for patients 65 years or older who underwent fusion of 8 or more vertebral levels from 2005 through 2012 (n = 3366). They calculated cumulative rates of the following complications during the first 6 weeks after surgery: cerebrovascular accident, congestive heart failure, deep venous thrombosis, myocardial infarction, pneumonia, and pulmonary embolism. Significance was set at p < 0.05.
During the perioperative period, rates of major medical complications were 5.9% for pneumonia, 4.1% for deep venous thrombosis, 3.2% for pulmonary embolism, 2.1% for cerebrovascular accident, 1.8% for myocardial infarction, and 1.0% for congestive heart failure. Mortality rates were 0.9% at 6 weeks and 1.8% at 2 years. When comparing the surgeon-maintained database with the Medicare & Medicaid Services claims database, there were no significant differences in the perioperative rates of major medical complications except pneumonia. Furthermore, there were no significant intergroup differences in the mortality rates at 6 weeks or 2 years. The SMD provided greater detail with respect to deformity characteristics and surgical variables than the MCD.
They conclude that the incidence of most major medical complications in the elderly after surgery for ASD was similar between the surgeon-maintained database and the Medicare & Medicaid Services claims database and ranged from 1% for congestive heart failure to 5.9% for pneumonia.
3 Tables
Ho P-R, Koendgen H, Campbell N, Haddock B, Richman S, Chang I. Risk of natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: a retrospective analysis of data from four clinical studies. Lancet Neurol. 2017;16(11):925-933. doi:10.1016/S1474-4422(17)30282-X.
Natalizumab is a highly efficacious and effective therapy for relapsing-remitting multiple sclerosis, as shown in clinical trials and real-world settings. However, natalizumab treatment is associated with a risk of developing progressive multifocal leukoencephalopathy (PML), a rare opportunistic infection caused by the John Cunningham virus (JCV). Three risk factors are known to affect a patient’s risk of developing natalizumab-associated PML: presence of anti-JCV antibodies in serum, immunosuppressant use before initiating natalizumab, and natalizumab treatment duration, especially beyond 2 years. The authors aimed to calculate PML risk estimates from patient-level risk-factor data and to stratify risk by concentrations of anti-JCV antibody in serum (anti-JCV antibody index). Data on natalizumab-treated patients were pooled from four large, observational, open-label studies: STRATIFY-2, STRATA, TOP, and TYGRIS. 156 (<1%) of 37,249 patients in the pooled cohort had PML. For anti-JCV antibody-negative patients (n=13,996), estimated PML risk was less than 0·07 per 1000 patients. In anti-JCV antibody-positive patients (n=21,696), estimated cumulative PML probability over 6 years (72 infusions of natalizumab) was 2·7% in patients with previous immunosuppressant use and 1·7% in those without. In patients without previous immunosuppressant use (n=18 616), estimated annual PML risks per 1000 patients, conditional on having no PML before that year, ranged from 0·01 in year 1 (1–12 infusions) to 0·6 in year 6 (61–72 infusions).
Consistent with previous natalizumab-associated PML risk estimates, this analysis showed that the risk increases with previous immunosuppressant exposure and longer natalizumab treatment. Risk estimates for years 5 and 6 appear to be higher than previous estimates because the life table method takes the higher discontinuation rate in these epochs into account. These new anti-JCV antibody index-stratified risk estimates suggest that PML risk remains low at index values of 0·9 or less and increases substantially at index values of more than 1·5. The results support recent clinical guidelines and consensus recommendations for additional MRI monitoring for natalizumab-treated patients with anti-JCV antibody index values of more than 0·9.
2 Tables, 3 figures
Zeestraten EA, Lawrence AJ, Lambert C, et al. Change in multimodal MRI markers predicts dementia risk in cerebral small vessel disease. Neurology. 2017;89(1526-632X (Electronic)):1-8. doi:10.1212/WNL.0000000000004594.
The purpose of this study was to determine whether MRI markers, including diffusion tensor imaging (DTI), can predict cognitive decline and dementia in patients with cerebral small vessel disease (SVD).
In the prospective St George’s Cognition and Neuroimaging in Stroke study, multimodal MRI was performed annually for 3 years and cognitive assessments annually for 5 years in a cohort of 99 patients with SVD, defined as symptomatic lacunar stroke and confluent white matter hyperintensities (WMH). Progression to dementia was determined in all patients. Progression of WMH, brain volume, lacunes, cerebral microbleeds, and a DTI measure (the normalized peak height of the mean diffusivity histogram distribution) as a marker of white matter microstructural damage were determined.
Over 5 years of follow-up, 18 patients (18.2%) progressed to dementia. A significant change in all MRI markers, representing deterioration, was observed. The presence of new lacunes, and rate of increase in white matter microstructural damage on DTI, correlated with both decline in executive function and global functioning. Growth of WMH and deterioration of white matter microstructure on DTI predicted progression to dementia.
Discriminant analysis in which age, sex, and premorbid IQ and vascular risk factors were entered did not discriminate between dementia converters and nonconverters. In contrast, discriminant analysis including the MRI variables found to be associated with progression to dementia in the previous multivariate Cox regression (i.e., change in mean diffusivity normalized peak height (MD-NP), WMH, and premorbid IQ) and their MRI baseline values was significant. It correctly classified 80.9% of patients with 80.0% sensitivity and 81.0% specificity and achieved an AUC of 0.849.
These results provide further support for the validity of MRI measures as surrogate markers in clinical trials evaluating new treatments for SVD. Currently there are few effective treatments for patients with SVD related cognitive decline. A major obstacle to assessing new treatments is the lack of detectable longitudinal change in cognition over short time periods. This has led to the suggestion that MRI measures may be useful to assess new therapies. Using MRI markers could markedly reduce sample sizes required to detect treatment effects.
In conclusion, this longitudinal prospective study provides evidence that change in MRI measures including DTI, over time durations during which cognitive change is not detectable, predicts cognitive decline and progression to dementia. It supports the use of MRI measures, including DTI, as useful surrogate biomarkers to monitor disease and assess therapeutic interventions.
3 Tables, 1 Figure
Natarajan SK, Shallwani H, Fennell VS, et al. Flow Diversion after Aneurysmal Subarachnoid Hemorrhage. Neurosurg Clin N Am. 2017;28(3):375-388. doi:10.1016/j.nec.2017.02.011.
Flow diversion is the placement of a low-porosity, high-mesh-density device in the parent vessel at the aneurysm neck to decrease flow into the aneurysm and redirect the flow to the distal part of the parent vessel. This method facilitates endothelialization of the flow-diverting device and subsequently excludes the aneurysm from the circulation over time. The Pipeline Embolization Device (PED; Medtronic, Minneapolis, MN) has been used for flow diversion in most of our patients because it is the only flow diverter approved by the Food and Drug Administration in the United States. The PED is a 48-wire, mesh-braided stent made of a radiolucent cobalt-chromium alloy, with every fourth strand made of radiopaque platinum-tungsten. Current flow diverters necessitate 3 months of dual antiplatelet therapy and lifelong aspirin to avoid in stent thrombosis.
Flow diversion after aneurysmal SAH is not preferred as the primary modality of treatment because of the risk associated with dual antiplatelet regimens in the setting of acute rupture. Moreover, the performance of invasive procedures in the preprocedural or periprocedural period, which may include the placement of an EVD, central line, shunt, tracheostomy, and/or percutaneous endoscopic gastrostomy tube, as well as a craniotomy for evacuation of hematoma and decompression, carries additional risk for patients who are receiving dual antiplatelet therapy. In addition, flow diversion does not achieve immediate aneurysm occlusion and does not decrease the chances of immediate rerupture compared with primary coiling or clipping.
In the setting of rupture, the authors goal is primarily to protect the dome of the aneurysm and obliterate high-risk regions like daughter sacs or focal outpouchings. A balance should be maintained between achieving packing density with coils that is sufficient to secure the aneurysm and avoiding aneurysm rupture or parent vessel compromise caused by excessive packing.
In summary, the authors consider flow diversion to not be the primary treatment of choice after aneurysmal SAH but is a reasonable last option if other, safer options are not available to treat the aneurysm. In the setting of acute aneurysm rupture, protection of the aneurysm dome followed by delayed flow diversion is a safer choice than primary flow diversion. The authors experience and review of the literature show the feasibility of flow diversion after aneurysmal SAH as primary treatment or in a subacute fashion after dome protection.
Rao G. Intraoperative MRI and Maximizing Extent of Resection. Neurosurg Clin N Am. 2017;28(4):477-485. doi:10.1016/j.nec.2017.05.003.
Nice review article which discusses rationale, history of intraoperative MR, literature review as well as cost and accessibility.
Both prospective and retrospective studies have demonstrated the utility of iMRI in enhancing the extent of resection. These studies have generally shown a benefit of iMRI for increasing the removal of enhancing disease, although there have been exceptions. For glioblastoma there have been 2 prospective studies evaluating the extent of resection in patients undergoing surgery for contrast-enhancing gliomas. In one of these studies (Senft et al) the extent of resection using iMRI was compared with conventional microsurgery as a control group. In this study, patients with contrast-enhancing gliomas were randomized to undergo surgery in the iMRI or a standard operating room. More patients (23/24, 96%) in the MRI group had a complete resection of their enhancing tumor compared with the control group (17/25, 68%). The median residual postoperative enhancing tumor was 0 cm3 in the iMRI group and 0.03 cm3 in the control group, a statistically significant difference. Progression-free survival was significantly longer in the iMRI group (226 days) compared with the control group (98 days). These investigators also showed that patients with a complete resection (regardless of group) had a significantly longer survival than those with an incomplete resection. In another prospective study of glioma resections in the iMRI environment (Hatiboglu et al) additional resection was performed in 21/26 (47%) patients because the intraoperative scan demonstrated residual disease. This additional resection resulted in an increase in the extent of resection from 84% to 99%.
