Faculty Bibliography

Background/UNASSIGNED:Pediatric intracranial aneurysms tend to differ in etiology, size, and location from their adult counterparts, and they are often less amenable to microsurgical clip reconstruction techniques. Endovascular treatment with detachable coils is an accepted treatment technique for pediatric patients, though high recurrence rates have been reported with coil embolization of large and giant aneurysms in this population. While the Pipeline Embolization Device (PED) is FDA-approved for adult intracranial aneurysms, the use of PEDs in pediatric patients is considered off-label. Case Descriptions/UNASSIGNED:We present 3 cases of pediatric intracranial aneurysms in a 5-year-old male, a 12-year-old male, and a 12-year-old female who presented with symptoms including seizure, headache, and blurred vision. The 2 male patients were found to have intradural vertebral artery saccular aneurysms, while the female patient had a paraophthalmic right internal carotid complex aneurysm. After endovascular reconstruction of the aneurysms with PEDs, follow-up angiography showed complete occlusion of the previous aneurysms with no residual aneurysm filling in all 3 cases. Conclusion/UNASSIGNED:While further investigation is needed, the evidence presented here supports the conclusion that the PED can be an effective and viable treatment strategy in the pediatric population.

BACKGROUND AND PURPOSE:Transcranial Doppler (TCD) criteria for cerebrovascular stenosis are only based on velocity with unsatisfactory positive predictive value (PPV) in previous studies. We refined a published scoring system that integrates several characteristics of TCD data in diagnosing middle cerebral artery (MCA) stenosis. METHODS:Using the TCD-digital subtraction angiography (DSA) database from Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial, velocity, spectrum pattern, diffuse ratio, and asymmetry ratio were assessed. The cutpoints were defined for each parameter and a point value was assigned to each category within that parameter. A summed score was calculated for each MCA. The accuracy was assessed for different cutpoints in predicting ≥50% MCA stenosis measured by DSA. Logistic regression and C-statistics were used for analysis. RESULTS:A total of 114 MCAs were included in vessel-based and 87 patients were included in patient-based analysis. Compared to the velocity-only cutpoints in SONIA, the score results in much improved PPV while negative predictive value (NPV) remains unchanged. The score based on mean velocity (score 0: <140 cm/s, score 3: ≥140 cm/s), spectrum pattern (score 0: no turbulence; score 1: mild turbulence; 2: significant turbulence), and asymmetry ratio (score 0: ratio <1.5, score 1: ratio 1.5-2; score 2: ratio ≥2.1) has the highest NPV while PPV remains favorable (PPV: 72% [95% CI 54-90%]; NPV: 84% [95% CI: 75-93%], area under curve [AUC]: .76 [95% CI: .66-.86]). CONCLUSIONS:The multiparameter scoring system incorporating several characteristics of TCD measures yielded higher PPV while maintaining high NPV compared with the single-parameter velocity criteria in diagnosing MCA ≥50% stenosis.

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Studies of sensorimotor integration often use sensory stimuli that require a simple motor response, such as a reach or a grasp. Recent advances in neural recording techniques, motion capture technologies, and time-synchronization methods enable studying sensorimotor integration using more complex sensory stimuli and performed actions. Here, we demonstrate that prehensile actions that require using complex sensory instructions for manipulating different objects can be characterized using high-density electroencephalography and motion capture systems. In 20 participants, we presented stimuli in different sensory modalities (visual, auditory) containing different contextual information about the object with which to interact. Neural signals recorded near motor cortex and posterior parietal cortex discharged based on both the instruction delivered and object manipulated. Additionally, kinematics of the wrist movements could be discriminated between participants. These findings demonstrate a proof-of-concept behavioral paradigm for studying sensorimotor integration of multidimensional sensory stimuli to perform complex movements. Such a framework will prove vital for studying neural control of movements in clinical populations in which sensorimotor integration is impaired due to information no longer being communicated correctly between brain regions (e.g. stroke). Such a framework is the first step towards developing a neural rehabilitative system for restoring function more effectively.

There is increasing recognition in the neurological and psychiatric literature of patients with so-called isolated psychotic presentations (ie, with no, or minimal, neurological features) who have tested positive for neuronal autoantibodies (principally N-methyl-D-aspartate receptor antibodies) and who have responded to immunotherapies. Although these individuals are sometimes described as having atypical, mild, or attenuated forms of autoimmune encephalitis, some authors feel that that these cases are sufficiently different from typical autoimmune encephalitis to establish a new category of so-called autoimmune psychosis. We briefly review the background, discuss the existing evidence for a form of autoimmune psychosis, and propose a novel, conservative approach to the recognition of possible, probable, and definite autoimmune psychoses for use in psychiatric practice. We also outline the investigations required and the appropriate therapeutic approaches, both psychiatric and immunological, for probable and definite cases of autoimmune psychoses, and discuss the ethical issues posed by this challenging diagnostic category.

OBJECTIVE:To assay EEG signal quality recorded with tripolar concentric ring electrodes (TCREs) compared to regular EEG electrodes. METHODS:EEG segments were recorded simultaneously by TCREs and regular electrodes, low-pass filtered at 35 Hz (REG35) and 70 Hz (REG70). Clips were rated blindly by nine electroencephalographers for presence or absence of key EEG features, relative to the "gold-standard" of the clinical report. RESULTS:TCRE showed less EMG artifact (F = 15.4, p < 0.0001). Overall quality rankings were not significantly different. Focal slowing was better detected by TCRE and spikes were better detected by regular electrodes. Seizures (n = 85) were detected by TCRE in 64 cases (75.3%), by REG70 in 75 (88.2%) and REG35 in 69 (81.2%) electrodes. TCRE detected 9 (10.6%) seizures not detected by one of the other 2 methods. In contrast, 14 seizures (16.5%) were not detected by TCRE, but were by REG35 electrodes. Each electrode detected interictal spikes when the other did not. CONCLUSIONS:TCRE produced similar overall quality and confidence ratings versus regular electrodes, but less muscle artifact. TCRE recordings detected seizures in 7% of instances where regular electrodes did not. SIGNIFICANCE/CONCLUSIONS:The combination of the two types increased detection of epileptiform events compared to either alone.

OBJECTIVE:To determine the influence of self-reported Black African and Latin American identity on peripheral blood antibody-secreting cell (ASC) frequency in the context of relapsing-remitting MS. METHODS:In this cross-sectional study, we recruited 74 subjects with relapsing-remitting MS and 24 age-, and self-reported ethno-ancestral identity-matched healthy donors (HDs) to provide peripheral blood study samples. Subjects with MS were either off therapy at the time of study draw or on monthly natalizumab therapy infusions. Using flow cytometry, we assessed peripheral blood mononuclear cells for antibody-secreting B-cell subsets. RESULTS:subsets, were among those significantly increased. CONCLUSION:The enhanced peripheral blood plasmablast signature revealed among Black African or Latin American subjects with MS points to distinct underlying mechanisms associated with MS immunopathogenesis. This dysregulation may contribute to the disease disparity experienced by patient populations of Black African or Latin American ethno-ancestry.

De novo mutations arising on the paternal chromosome make the largest known contribution to autism risk, and correlate with paternal age at the time of conception. The recurrence risk for autism spectrum disorders is substantial, leading many families to decline future pregnancies, but the potential impact of assessing parental gonadal mosaicism has not been considered. We measured sperm mosaicism using deep-whole-genome sequencing, for variants both present in an offspring and evident only in father's sperm, and identified single-nucleotide, structural and short tandem-repeat variants. We found that mosaicism quantification can stratify autism spectrum disorders recurrence risk due to de novo mutations into a vast majority with near 0% recurrence and a small fraction with a substantially higher and quantifiable risk, and we identify novel mosaic variants at risk for transmission to a future offspring. This suggests, therefore, that genetic counseling would benefit from the addition of sperm mosaicism assessment.

OBJECTIVES/OBJECTIVE:This study aims to investigate the role and mechanism of FGFR3 in macrophages and their biological effects on the pathology of arthritis. METHODS:Mice with conditional knockout of FGFR3 in myeloid cells (R3cKO) were generated. Gait behaviours of the mice were monitored at different ages. Spontaneous synovial joint destruction was evaluated by digital radiographic imaging and μCT analysis; changes of articular cartilage and synovitis were determined by histological analysis. The recruitment of macrophages in the synovium was examined by immunostaining and monocyte trafficking assay. RNA-seq analysis, Western blotting and chemotaxis experiment were performed on control and FGFR3-deficient macrophages. The peripheral blood from non-osteoarthritis (OA) donors and patients with OA were analysed. Mice were treated with neutralising antibody against CXCR7 to investigate the role of CXCR7 in arthritis. RESULTS:R3cKO mice but not control mice developed spontaneous cartilage destruction in multiple synovial joints at the age of 13 months. Moreover, the synovitis and macrophage accumulation were observed in the joints of 9-month-old R3cKO mice when the articular cartilage was not grossly destructed. FGFR3 deficiency in myeloid cells also aggravated joint destruction in DMM mouse model. Mechanically, FGFR3 deficiency promoted macrophage chemotaxis partly through activation of NF-κB/CXCR7 pathway. Inhibition of CXCR7 could significantly reverse FGFR3-deficiency-enhanced macrophage chemotaxis and the arthritic phenotype in R3cKO mice. CONCLUSIONS:Our study identifies the role of FGFR3 in synovial macrophage recruitment and synovitis, which provides a new insight into the pathological mechanisms of inflammation-related arthritis.