Synopsis of Guidelines for the Clinical Management of Cerebral Cavernous Malformations: Consensus Recommendations based on Systematic Literature Review by the Angioma Alliance Scientific Advisory Board Clinical Experts Panel

BackgroundDespite many publications about cerebral cavernous malformations (CCMs), controversy remains regarding diagnostic and management strategies.ObjectiveTo develop guidelines for CCM management.MethodsThe Angioma Alliance ( www.angioma.org ), the patient support group in the United States advocating on behalf of patients and research in CCM, convened a multidisciplinary writing group comprising expert CCM clinicians to help summarize the existing literature related to the clinical care of CCM, focusing on 5 topics: (1) epidemiology and natural history, (2) genetic testing and counseling, (3) diagnostic criteria and radiology standards, (4) neurosurgical considerations, and (5) neurological considerations. The group reviewed literature, rated evidence, developed recommendations, and established consensus, controversies, and knowledge gaps according to a prespecified protocol.ResultsOf 1270 publications published between January 1, 1983 and September 31, 2014, we selected 98 based on methodological criteria, and identified 38 additional recent or relevant publications. Topic authors used these publications to summarize current knowledge and arrive at 23 consensus management recommendations, which we rated by class (size of effect) and level (estimate of certainty) according to the American Heart Association/American Stroke Association criteria. No recommendation was level A (because of the absence of randomized controlled trials), 11 (48%) were level B, and 12 (52%) were level C. Recommendations were class I in 8 (35%), class II in 10 (43%), and class III in 5 (22%).ConclusionCurrent evidence supports recommendations for the management of CCM, but their generally low levels and classes mandate further research to better inform clinical practice and update these recommendations. The complete recommendations document, including the criteria for selecting reference citations, a more detailed justification of the respective recommendations, and a summary of controversies and knowledge gaps, was similarly peer reviewed and is available on line www.angioma.org/CCMGuidelines

Surgical clipping of a non-ruptured ophthalmic aneurysm through an extradural micropterional keyhole approach

Background Clipping continues to be one of the treatment strategies for ophthalmic artery aneurysms not amenable for stenting or coiling, or when long-term treatment durability is a concern. However, crescent development of endovascular techniques demands minimal invasiveness in the transcranial approaches while ensuring satisfactory results. Methods We describe an extradural micropterional keyhole approach (eMKA) to the paraclinoid region and highlight the key anatomical elements of this surgical approach. Conclusion The eMKA is a minimally invasive approach that provides access to the paraclinoid region using an extradural corridor. Therefore, it is suitable for clipping of ophthalmic artery aneurysms and other paraclinoid aneurysms

Radiation-induced meningiomas: A case-control study at single center institution

Our understanding of radiation induced meningiomas (RIM) is limited. It has been suggested that RIM harbor more aggressive cellular pathology and must be observed vigilantly. However, the actual recurrence rates of RIM compared to the sporadic meningiomas has yet to be defined. We employ a single center case-control study to retrospectively assess recurrence rates between RIM (n = 12) and sporadic meningiomas (n = 118). The criteria for the RIM group included the following: 1) History of intracranial clinical-dose radiation 2) Initial pathology other than meningioma, 3) Radiation administered greater than 5 years prior to meningioma onset. Recurrence rates, extent of resection and outcomes were analyzed. There was a significant difference in recurrence rates between the RIM group and sporadic meningioma: 50% vs. 5% respectively, p = 0.004. There was no significant difference in race, preoperative tumor volume, extent of resection, Ki67, or age between the two groups. Multivariate analysis demonstrated that size (OR 0.95 95%CI (0.92-0.99)), extent of resection (OR 1.08 95%CI (1.01-1.14)), WHO grade (OR 160.24 95% CI (6.32-74509)) and history of previous radiation (OR 1.28 95%CI (1.01-1.62)) were independent risk factors for recurrence. RIM patients had significantly higher proportion of atypical or malignant histology compared to sporadic patients (p < 0.0001). RIM patients may have a higher predisposition for tumor recurrence than patients with sporadic RIM. The use of Ki67 indices may help identify patients with a higher risk of tumor recurrence. Prospective studies focusing on newly diagnosed patients with RIM may help identify an optimal surveillance and treatment plan

Alzheimer’s disease pathology and shunt surgery outcome in normal pressure hydrocephalus

We aimed to determine whether presence of AD neuropathology predicted cognitive, gait and balance measures in patients with idiopathic normal pressure hydrocephalus (iNPH) after shunt surgery. This is a prospective study of gait and balance measured by Timed Up and Go (TUG) and Tinetti tests, and cognitive function measured by Mini Mental Status Exam (MMSE), before and after shunt surgery in participants 65 years and older with iNPH at the Johns Hopkins University. Random effects models were used and adjusted for confounders. 88 participants were included in the analysis with a median (IQR) time of 104 (57–213) days between surgery and follow-up. 23 (25%) participants had neuritic plaques present (NP+) and were significantly older [76.4 (6.0) years], but were otherwise similar in all demographics and outcome measures, when compared to the group without neuritic plaques (NP-). NP- and NP+ participants equally improved on measures of TUG (β = -3.27, 95% CI -6.24, -0.30, p = 0.03; β = -2.37, 95% CI -3.90, -0.86, p = 0.02, respectively), Tinetti-total (β = 1.95, 95% CI 1.11, 2.78, p<0.001; β = 1.72, 95% CI 0.90, 2.53, p<0.001, respectively), -balance (β = 0.81, 95% CI 0.23, 1.38, p = 0.006; β = 0.87, 95% CI 0.40, 1.34, p<0.001, respectively) and -gait (β = 1.03, 95% CI 0.61, 1.45, p<0.001; β = 0.84, 95% CI 0.16, 1.53, p = 0.02, respectively), while neither NP- nor NP+ showed significant improvement on MMSE (β = 0.10, 95% CI -0.27, 0.46, p = 0.61, β = 0.41, 95% CI -0.27, 1.09, p = 0.24, respectively). In summary, 26% of participants with iNPH had coexisting AD pathology, which does not significantly influence the clinical response to shunt surgery

Methodological and analytical considerations for intra-operative microdialysis

Abstract Background Microdialysis is a technique that can be utilized to sample the interstitial fluid of the central nervous system (CNS), including in primary malignant brain tumors known as gliomas. Gliomas are mainly accessible at the time of surgery, but have rarely been analyzed via interstitial fluid collected via microdialysis. To that end, we obtained an investigational device exemption for high molecular weight catheters (HMW, 100 kDa) and a variable flow rate pump to perform microdialysis at flow rates amenable to an intra-operative setting. We herein report on the lessons and insights obtained during our intra-operative HMW microdialysis trial, both in regard to methodological and analytical considerations. Methods Intra-operative HMW microdialysis was performed during 15 clinically indicated glioma resections in fourteen patients, across three radiographically diverse regions in each patient. Microdialysates were analyzed via targeted and untargeted metabolomics via ultra-performance liquid chromatography tandem mass spectrometry. Results Use of albumin and lactate-containing perfusates impacted subsets of metabolites evaluated via global metabolomics. Additionally, focal delivery of lactate via a lactate-containing perfusate, induced local metabolic changes, suggesting the potential for intra-operative pharmacodynamic studies via reverse microdialysis of candidate drugs. Multiple peri-operatively administered drugs, including levetiracetam, cefazolin, caffeine, mannitol and acetaminophen, could be detected from one microdialysate aliquot representing 10 min worth of intra-operative sampling. Moreover, clinical, radiographic, and methodological considerations for performing intra-operative microdialysis are discussed. Conclusions Intra-operative HMW microdialysis can feasibly be utilized to sample the live human CNS microenvironment, including both metabolites and drugs, within one surgery. Certain variables, such as perfusate type, must be considered during and after analysis. Trial registration NCT0404726

ORAL PRESENTATION Open Access

Asymptomatic ventricular dilatation precedes clinical decline in rodent adult chronic communicating hydrocephalu

Random effects analysis for gait scores before and after large volume ELD trial by neuritic plaque status.

<p>Random effects analysis for gait scores before and after large volume ELD trial by neuritic plaque status.</p

Gait and cognitive measures before and after large volume ELD by neuritic plaque status.

<p>Gait and cognitive measures before and after large volume ELD by neuritic plaque status.</p

Random effects for cognitive and gait scores before large volume ELD trial and after surgery by neuritic plaque status.

<p>Random effects for cognitive and gait scores before large volume ELD trial and after surgery by neuritic plaque status.</p