Flemming, Kelly D.

Incidental vascular lesions are being discovered at an increasing frequency due to widespread noninvasive brain imaging studies. One of these lesions has recently been termed a “pure arterial malformation” (PAM), which is defined as dilated, overlapping, and tortuous arteries forming a mass of arterial loops with a coil-like appearance in the absence of arteriovenous shunting. The pathogenesis of these lesions is not known, but a congenital etiology is suspected. The authors report the case of a 17-year-old female who was found to have a PAM of the posterior inferior cerebellar artery with adipose tissue interspersed within the arterial loops. The authors believe that this abnormal intracranial association between blood vessel and adipose tissue lends further support to the theory that PAMs are the result of a congenital malformation and are therefore safe to manage conservatively given their presumed benign natural history. Far from offering conclusive evidence, this unique case report adds to the growing body of PAM literature and strengthens an increasingly supported congenital theory of genesis.

Abstract BACKGROUND Brain cavernous angiomas with symptomatic hemorrhage (CASH) are uncommon but exact a heavy burden of neurological disability from recurrent bleeding, for which there is no proven therapy. Candidate drugs to stabilize the CASH lesion and prevent rebleeding will ultimately require testing of safety and efficacy in multisite clinical trials. Much progress has been made in understanding the epidemiology of CASH, and novel biomarkers have been linked to the biological mechanisms and clinical activity in lesions. Yet, the ability to enroll and risk-stratify CASH subjects has never been assessed prospectively at multiple sites. Biomarkers and other outcomes have not been evaluated for their sensitivity and reliability, nor have they been harmonized across sites. OBJECTIVE To address knowledge gaps and establish a research network as infrastructure for future clinical trials, through the Trial Readiness grant mechanism, funded by National Institute of Neurological Disorders and Stroke/National Institutes of Health. METHODS This project includes an observational cohort study to assess (1) the feasibility of screening, enrollment rates, baseline disease categorization, and follow-up of CASH using common data elements at multiple sites, (2) the reliability of imaging biomarkers including quantitative susceptibility mapping and permeability measures that have been shown to correlate with lesion activity, and (3) the rates of recurrent hemorrhage and change in functional status and biomarker measurements during prospective follow-up. EXPECTED OUTCOMES We propose a harmonized multisite assessment of enrollment rates of CASH, baseline features relevant to stratification in clinical trials, and follow-up assessments of functional outcomes in relation to clinical bleeds. We introduce novel biomarkers of vascular leak and hemorrhage, with firm mechanistic foundations, which have been linked to clinical disease activity. We shall test their reliability and validity at multiple sites, and assess their changes over time, with and without clinical rebleeds, hence their fitness as outcome instruments in clinical trials. DISCUSSION The timing cannot be more opportune, with therapeutic targets identified, exceptional collaboration among researchers and the patient community, along with several drugs ready to benefit from development of a path to clinical testing using this network in the next 5 years.

Background and Purpose— Superficial siderosis (SS) is characterized by hemosiderin deposition in the superficial layers of the central nervous system and can be seen during postmortem examination or with iron-sensitive magnetic resonance imaging techniques. The distribution of SS may predict the probable underlying cause. This study aimed to report the prevalence and natural history of SS in a population-based study. Methods— Brain magnetic resonance imaging scans from the MCSA (Mayo Clinic Study of Aging), a population-based study of residents 50 to 89 years of age in Olmsted County, Minnesota, were reviewed. Participants with imaging consistent with SS were identified from 2011 through 2016. An inverse probability weighting approach was used to convert our observed frequencies to population prevalence of SS. Additional data abstracted included amyloid positron emission tomography, Apolipoprotein E genotype, coexisting cerebral microbleeds, and extent of SS. Results— A total of 1412 participants had eligible magnetic resonance imaging scans. Two participants had infratentorial SS, restricted to the posterior fossa. Thirteen participants had cortical SS involving the cerebral convexities (7 focal and 6 disseminated). Only 3 of the participants with cortical SS (23%) also had cerebral microbleeds. The population prevalence of SS was 0.21% (95% confidence interval, 0–0.45) in those 50 to 69 years old and 1.43% (confidence interval, 0.53–2.34) in those over 69 years old. Apolipoprotein E ε2 allele was more common in those with SS (57.1% versus 15.0%; P <0.001). Compared with participants without SS, those with SS were also more likely to have a positive amyloid positron emission tomographic scan (76.9% versus 29.8%; P <0.001). Conclusions— SS may be encountered in the general elderly population. The association with increased amyloid burden and Apolipoprotein E ε2 genotype supports cerebral amyloid angiopathy as the most common mechanism. Longitudinal follow-up is needed to evaluate the risk of subsequent hemorrhage in cases of incidentally discovered SS.

OBJECTIVEOver the last half century, there have been isolated case reports of purely arterial malformations. In this study, the authors report a consecutive series of patients with pure arterial malformations, emphasizing the clinical and radiological features of these lesions.METHODSPure arterial malformations were defined as dilated, overlapping, and tortuous arteries with a coil-like appearance and/or a mass of arterial loops without any associated venous component. Demographic characteristics of the patients, cardiovascular risk factors, presentation, radiological characteristics, and follow-up data were collected. Primary outcomes were new neurological symptoms including disability, stroke, and hemorrhage.RESULTSTwelve patients meeting the criteria were identified. Ten patients were female (83.3%) and 2 were male (16.6%). Their mean age at diagnosis was 26.2 ± 11.6 years. The most common imaging indication was headache (7 patients [58.3%]). In 3 cases the pure arterial malformation involved the anterior cerebral arteries (25.0%); in 4 cases the posterior communicating artery/posterior cerebral artery (33.3%); in 2 cases the middle cerebral artery (16.6%); and in 1 case each, the superior cerebellar artery, basilar artery/anterior inferior cerebellar artery, and posterior inferior cerebellar artery. The mean maximum diameter of the malformations was 7.2 ± 5.0 mm (range 3–16 mm). Four lesions had focal aneurysms associated with the pure arterial malformation, and 5 were partially calcified. In no cases was there associated intracranial hemorrhage or infarction. One patient underwent treatment for the pure arterial malformation. All 12 patients had follow-up (mean 29 months, median 19 months), and there were no cases of disability, stroke, or hemorrhage.CONCLUSIONSPure arterial malformations are rare lesions that are often detected incidentally and probably have a benign natural history. These lesions can affect any of the intracranial arteries and are likely best managed conservatively.

The authors report a case of a developmentally normal child with a congenital complex torcular dural arteriovenous fistula (DAVF) who later, in his teenage years, developed several vermian cavernomas within a large cerebellar developmental venous anomaly (DVA). The patient had initially presented with an abnormally large head circumference but no neurological deficits. He underwent several partial embolization procedures in an attempt to decrease the blood supply of the fistula over the course of 8 years. Nine years following initial presentation, he presented with a fourth ventricular hemorrhage, due to development of a new vermian cavernoma adjacent to a previously known vermian DVA and suffered subsequent mild left-sided hemiataxia from which he later recovered. CT angiographic images demonstrated that the vermian DVA drained into the left transverse sinus, which also drained the torcular arteriovenous fistula. A routine follow-up MRI examination 10 years following initial presentation demonstrated interval development of several large cavernomas in the cerebellum, all within the DVA. The patient had no new symptoms at that time and was neurologically intact. This case report highlights the de novo development of multiple cavernous malformations potentially secondary to DAVF-induced venous congestion in a preexisting DVA.

Abstract BACKGROUND: Despite many publications about cerebral cavernous malformations (CCMs), controversy remains regarding diagnostic and management strategies. OBJECTIVE: To develop guidelines for CCM management. METHODS: The 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. RESULTS: Of 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%). CONCLUSION: Current 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.

PurposeEarly identification of ischemic stroke plays a significant role in treatment and potential recovery of damaged brain tissue. In noncontrast CT (ncCT), the differences between ischemic changes and healthy tissue are usually very subtle during the hyperacute phase (< 8 h from the stroke onset). Therefore, visual comparison of both hemispheres is an important step in clinical assessment. A quantitative symmetry‐based analysis of texture features of ischemic lesions in noncontrast CT images may provide an important information for differentiation of ischemic and healthy brain tissue in this phase.MethodsOne hundred thirty‐nine (139) ncCT scans of hyperacute ischemic stroke with follow‐up magnetic resonance diffusion‐weighted (MR‐DW) images were collected. The regions of stroke were identified in the MR‐DW images, which were spatially aligned to corresponding ncCT images. A state‐of‐the‐art symmetric diffeomorphic image registration was utilized for the alignment of CT and MR‐DW, for identification of individual brain hemispheres, and for localization of the region representing healthy tissue contralateral to the stroke cores. Texture analysis included extraction and classification of co‐occurrence and run‐length texture‐based image features in the regions of ischemic stroke and their contralateral regions.ResultsThe classification schemes achieved area under the receiver operating characteristic [Az] ≈ 0.82 for the whole dataset. There was no statistically significant difference in the performance of classifiers for the data sets with time between 2 and 8 hours from symptom onset. The performance of the classifiers did not depend on the size of the stroke regions.ConclusionsThe results provide a set of optimal texture features which are suitable for distinguishing between hyperacute ischemic lesions and their corresponding contralateral brain tissue in noncontrast CT. This work is an initial step toward development of an automated decision support system for detection of hyperacute ischemic stroke lesions on noncontrast CT of the brain.