Kumar, Gyanendra

Introduction: The lack of understanding about the genetic and molecular basis of young stroke (<55 years of age) has hindered development of diagnostic, management, and therapeutic approaches. Whole exome sequencing (WES) can be leveraged as a tool for studying etiological processes underlying stroke. At the time of study inception, this is the single largest WES study in this unique young stroke population to uncover elusive stroke etiologies. Methods: The Mayo Clinic TAPESTRY database is a research program conducting whole exome sequencing of 100,000 participants. Of these, 406 participants met the criteria for young stroke (18-54 years of age) based on ICD-9 and ICD-10 diagnostic codes. Controls were TAPESTRY participants without a stroke-related ICD diagnosis. Cases were matched for age, gender, and race for a 1:4 case-control ratio. Ischemic stroke etiology was classified using TOAST classification. To uncover genetic mechanisms, a gene centric approach was used to identify variants in our cohort. A list of 66 genes known to be associated with young stroke was curated based on existing genetic databases. Various filtration strategies were used to identify potentially damaging variants (graphic 1). Results: There were 406 cases (363 ischemic and 43 hemorrhagic; 291 female; age at stroke onset 39.8±10.4; 368 were White) and 3,857 controls. TOAST classification yielded 20 patients with large artery atherosclerosis, 58 cardioembolic, 10 small vessel disease, 148 other determined (58 patent foramen ovale, 50 dissection, 48 hypercoagulable state, 11 Moyamoya, 11 vasculitis, 10 fibromuscular dysplasia), and 165 undetermined etiologies. Several individuals had multiple competing etiologies. Of cerebral hemorrhages, there were 6 aneurysmal, 6 arteriovenous malformation, 5 hypertensive, 2 substance abuse, 3 trauma, and 21 other etiologies. Across the entire cohort, 35,054 variants were found within the 66 genes identified from the literature. Filtration identified 48 potentially damaging variants across 30 genes in 44 patients (20 cryptogenic and 21 other: 12 patent foramen ovale, 5 vasculitis, 4 dissection, 4 cardioembolic) that were absent in controls. Conclusion: WES is a powerful tool that can be used to uncover potential genetic mechanisms in the young stroke population. An improved understanding of etiologies would improve diagnostics and pave the way for new preventive and therapeutic approaches, thus improving the overall care of young stroke patients.

ABSTRACTBACKGROUND AND PURPOSEInvestigation for patent foramen ovale (PFO) is warranted in patients with cryptogenic stroke (CS), as PFO closure is recommended in select CS patients for secondary stroke prevention. Transcranial Doppler (TCD) is noninvasive and has high sensitivity for PFO screening. However, 10% of the population has insufficient temporal bone windows to perform standard TCD monitoring of the middle cerebral arteries (MCAs). Prior reports showed similar diagnostic accuracy between the basilar artery and MCAs insonation. Our objective was to assess the accuracy of transforaminal insonation of the basilar artery (TIBA) in diagnosis of right‐to‐left shunt (RLS) in patients with inadequate temporal windows.METHODSWe performed a retrospective, single‐center, observational study of TIBA in patients with CS and inadequate temporal windows. We compared the PFO screening accuracy using TIBA versus echocardiogram, either transthoracic (TTE) or transesophageal echocardiogram (TEE).RESULTSSixteen females and four males were included (mean age 63.2). All patients underwent TTE, 10 (50%) underwent gold‐standard TEE. Nine patients had positive PFO with both TCD and echocardiogram. Two patients with negative echocardiogram had TCD‐positive shunt. Three patients had PFO present on echocardiogram, whereas TCD was negative. Six patients had absent shunt with both TCD and echocardiogram. The sensitivity and specificity of TIBA for RLS detection were 75%, positive predictive value 82%, and negative predictive value 67%.CONCLUSIONPFO screening accuracy using TIBA was 75%. Prospective evaluation of CS patients with TIBA and comparison to the gold‐standard TEE should be performed to further guide clinical practice.

Abstract Neurological instability during the first days following ischemic stroke reflects the potential to salvage brain tissue at risk for infarct growth, hemorrhagic transformation, or malignant edema. However, current clinical care provides intermittent assessments on the order of at least an hour apart potentially missing the early detection of neurological deterioration. Optical imaging offers a continuous, portable alternative to the current combination of physical exams and radiological imaging. However, optical imaging technology has heretofore lacked the crucial combination of portability, resolution, and coverage required for assessing distributed brain function. Here, we present a portable high-density diffuse optical tomography (HD-DOT) system that overcomes these limitations to assess neurological disruption at the bedside. We imaged patients within 72 hours after ischemic stroke onset and demonstrate that HD-DOT is sensitive to both the presence of stoke (Cohen’s d = 1.5, p = 1.2 × 10− 3) as well as the degree of neurological disruption measured by NIH Stroke Scale (R2 = 0.69, p = 4.7 × 10− 4).

ObjectivesSilent cerebral artery vasospasm in aneurysmal subarachnoid hemorrhage causes serious complications such as cerebral ischemia and death. A transcranial Doppler (TCD) ultrasound system is a noninvasive device that can effectively detect cerebral artery vasospasm as soon as it sets in, even before and in the absence of clinical deterioration. Continuous or even daily TCD monitoring is challenging because of the operator expertise and certification required in the form of a trained sonographer and interpretive experience required in the form of an additionally trained and certified physician to perform these studies. This barrier exists because of a lack of automation for detection (without human intervention) of cerebral artery vasospasm using TCD ultrasound. To overcome this barrier, we present an algorithm that automates detection of cerebral artery vasospasm.MethodsWe extracted features such as the energy, energy entropy, zero‐crossing rate, spectral centroid, spectral speed, spectral entropy, spectral flux, spectral roll‐off, harmonic ratio, chroma, and Mel frequency cepstral coefficients for signal classification. Then we applied principal component analysis to reduce the data dimensionality.ResultsAll of the chosen features were used for training a decision‐tree classifier. The algorithm had high accuracy for cerebral artery vasospasm detection, with overall sensitivity of 87.5% and specificity of 89.74%.ConclusionsThe algorithm has the potential for development into a continuous cerebral artery vasospasm monitor.