Faculty Bibliography

OBJECTIVE:To assess the proportion of pediatric patients who develop post-traumatic stress disorder (PTSD) attributed to traumatic brain injury (TBI). METHODS:PubMed and Embase were searched from database inception until January 26, 2019. Two independent investigators screened titles, abstracts, and subsequently, full-text articles. Following this, the same investigators also extracted data relevant for the scope of this review. RESULTS:Ten articles were included in this review. In these, six unique cohorts were described, with relative frequencies of PTSD attributed TBI ranging from 3.3% to 48.5%. Two studies also found that PTSD was more common in children after TBI compared to pediatric orthopedic controls. Study quality was determined as high or very high for all six included cohorts, although the studies differed considerably in terms of methodology. CONCLUSIONS:Methodological variations confound comparisons of relative frequency assessments of PTSD attributed to TBI. However, PTSD is associated with considerable long-term disability and undetected PTSD in children should raise public concern. Thus, large scale, prospective studies are needed to ascertain the clinical course of PTSD attributed to TBI in children and adolescence.

Enrichment of sodium channels at nodes of Ranvier, a hallmark of myelinated axons, underlies effective saltatory conduction. In this issue of Neuron, Eshed-Eisenbach et al. (2020) demonstrate that proteolysis of gliomedin, which drives initial channel clustering, provides a novel mechanism to ensure fidelity of channel localization to nodes.

OBJECTIVE:To evaluate the efficacy and safety of adjunctive cenobamate 200 mg/d in patients with uncontrolled focal (partial-onset) seizures despite treatment with 1 to 3 antiepileptic drugs. METHODS:In this multicenter, double-blind, placebo-controlled study, adults 18 to 65 years of age with focal seizures were randomized 1:1 (cenobamate:placebo) after an 8-week baseline period. The 12-week double-blind treatment period consisted of a 6-week titration phase and a 6-week maintenance phase. The primary outcome was percent change in seizure frequency (from baseline) per 28 days during double-blind treatment. RESULTS:< 0.0001). Focal seizures with motor component, impaired awareness, and focal to bilateral tonic-clonic seizures were significantly reduced with cenobamate vs placebo. During maintenance, 28.3% of cenobamate-treated and 8.8% of placebo-treated patients were seizure-free. Treatment-emergent adverse events reported in >10% in either group (cenobamate vs placebo) were somnolence (22.1% vs 11.9%), dizziness (22.1% vs 16.5%), headache (12.4% vs 12.8%), nausea (11.5% vs 4.6%), and fatigue (10.6% vs 6.4%). CONCLUSION/CONCLUSIONS:Adjunctive treatment with cenobamate 200 mg/d significantly improved seizure control in adults with uncontrolled focal seizures and was well tolerated. CLINICALTRIALSGOV IDENTIFIER/UNASSIGNED:NCT01397968. CLASSIFICATION OF EVIDENCE/METHODS:This study provides Class I evidence that, for patients with uncontrolled focal seizures, adjunctive cenobamate reduces seizures.

It is a commonplace that evolution proceeds by selection of the fittest with elimination of organisms less well adapted to the environment. Along with this, the appearance of novel form arises from preliminary stages in growth, not as additions to the endpoints of prior specialization. The mechanisms of evolutionary change, from earlier form-building layers and specification by elimination, have been described in morphogenesis as prolongation of pre-terminal stages in development and winnowing of redundancy to achieve specific-ity. In earlier writings, these trends in evolutionary and developmental growth were the basis of an account of the nature of the symptom (error) with focal brain lesion. This paper extends the argument from pathology to subjective experience, namely that patterns in evolutionary and fetal growth that are carried over into adult cognition can explain the emergence of intrapersonal phenomena in human mind conceived as a kind of organism, with activity in the mental (mind/brain) state interpreted as a dynamic process of growth.

Neurons are highly polarized cells organized into functionally and molecularly distinct domains. A key question is whether the multiprotein complexes that comprise these domains are preassembled, transported, and inserted as a complex or whether their components are transported independently and assemble locally. Here, we have dynamically imaged, in pairwise combinations, the vesicular transport of fluorescently tagged components of the nodes of Ranvier and other myelinated axonal domains in sensory neurons cultured alone or together with Schwann cells at the onset of myelination. In general, most proteins are transported independently in the anterograde direction. In contrast, there is substantial cotransport of proteins from distinct domains in the retrograde direction likely due to coendocytosis along the axon. Early myelination did not substantially change these patterns of transport, although it increased the overall numbers of axonal transport vesicles. Our results indicate domain components are transported in separate vesicles for local assembly, not as preformed complexes, and implicate endocytosis along axons as a mechanism of clearance.

BACKGROUND AND PURPOSE/OBJECTIVE:The Neuroform Atlas is a new microstent to assist coil embolization of intracranial aneurysms that recently gained FDA approval. We present a postmarket multicenter analysis of the Neuroform Atlas stent. MATERIALS AND METHODS/METHODS:On the basis of retrospective chart review from 11 academic centers, we analyzed patients treated with the Neuroform Atlas after FDA exemption from January 2018 to June 2019. Clinical and radiologic parameters included patient demographics, aneurysm characteristics, stent parameters, complications, and outcomes at discharge and last follow-up. RESULTS:= .03). CONCLUSIONS:This multicenter analysis provides a real-world safety and efficacy profile for the treatment of intracranial aneurysms with the Neuroform Atlas stent.

In health and disease, the somatosensory system has been interrogated with standardized research techniques, collectively referred to as quantitative sensory testing (QST). In neuropathic pain, QST has been used to characterize multiple sensory derangements. However, the use of QST outside the lab has been limited by several factors, including a lack of standardization, variability in procedural technique, and duration of testing that would be unacceptable for clinic. To address these shortcomings, the Neuropathic Pain Research Consortium (NPRC) designed an easy and low-cost "bedside" QST procedure. To test the hypothesis that this procedure would be clinically reliable over time and across different examiners, a multi-site, blinded study was performed in subjects with postherpetic neuralgia. Generally, agreement between two examiners and over two study visits with one examiner was high. Additionally, intraclass correlation coefficients and Kappa statistics calculated showed that the battery of QST tests included were highly reliable. Interestingly, mechanical modalities (light brush, pinprick, pressure, and vibration) showed the highest reliability. The least reliable modalities were cool (room temperature) and warmth (38°C). These data demonstrate that the NPRC beside QST protocol is reliable across examiner and over time, providing a validated QST tool for use in clinical practice and clinical trials. Perspective: This blinded, multi-center trial in 32 patients with postherpetic neuralgia demonstrates bedside quantitative sensory testing is reliable and suitable as a clinical trial outcome. The novel bedside battery could be used in clinical trials or in clinical practice over time given the reliability data presented in this article.