Faculty Bibliography

The incidence of childhood central nervous system tumors in infants is about 6 per 100 000 children. Recent studies have showed recurrent fusion of the neurotrophic tyrosine receptor kinase (NTRK) gene in 10% of non-brainstem high grade glioma in very young children suggesting an oncogenic effect of the NTRK fusion genes. In this report, we present a rare, severe case of a full-term neonate who was noted to have widely splayed sutures and a bulging fontanelle at birth who was found to have infant-type hemispheric glioma with NTRK1 fusion with course complicated by seizures refractory to medical treatment. Patient was deemed a poor surgical candidate due to the size of the mass and thus parents opted for comfort care.

In efforts to understand the cognitive heterogeneity within and across epilepsy syndromes, cognitive phenotyping has been proposed as a new taxonomy aimed at developing a harmonized approach to cognitive classification in epilepsy. Data- and clinically driven approaches have been previously used with variability in the phenotypes derived across studies. In our study, we utilize latent profile analysis to test several models of phenotypes in a large multicentre sample of patients with temporal lobe epilepsy and evaluate their demographic and clinical profiles. For the first time, we examine the added value of replacing missing data and examine factors that may be contributing to missingness. A sample of 1178 participants met the inclusion criteria for the study, which included a diagnosis of temporal lobe epilepsy and the availability of comprehensive neuropsychological data. Models with two to five classes were examined using latent profile analysis and the optimal model was selected based on fit indices, posterior probabilities and proportion of sample sizes. The models were also examined with imputed data to investigate the impact of missing data on model selection. Based on the fit indices, posterior probability and distinctiveness of the latent classes, a three-class solution was the optimal solution. This three-class solution comprised a group of patients with multidomain impairments, a group with impairments predominantly in language and a group with no impairments. Overall, the multidomain group demonstrated a worse clinical profile and comprised a greater proportion of patients with mesial temporal sclerosis, a longer disease duration and a higher number of anti-seizure medications. The four-class and five-class solutions demonstrated the lowest probabilities of a group membership. Analyses with imputed data demonstrated that the four-class solution was the optimal solution; however, there was a weak agreement between the missing and imputed data sets for the four-Class solutions (κ = 0.288, P < 0.001). This study represents the first to use latent profile analysis to test and compare multiple models of cognitive phenotypes in temporal lobe epilepsy and to determine the impact of missing data on model fit. We found that the three-phenotype model was the most meaningful based on several fit indices and produced phenotypes with unique demographic and clinical profiles. Our findings demonstrate that latent profile analysis is a rigorous method to identify phenotypes in large, heterogeneous epilepsy samples. Furthermore, this study highlights the importance of examining the impact of missing data in phenotyping methods. Our latent profile analysis-derived phenotypes can inform future studies aimed at identifying cognitive phenotypes in other neurological disorders.

BACKGROUND/UNASSIGNED:Our hypothesis was that lumbar adhesive arachnoiditis (AA)/chronic lumbar AA (CAA) are clinical diagnoses that do not require radiographic confirmation. Therefore, patients with these syndromes do not necessarily have to demonstrate significant radiographic abnormalities on myelograms, MyeloCT studies, and/or MR examinations. When present, typical AA/CAA findings may include; central or peripheral nerve root/cauda equina thickening/clumping (i.e. latter empty sac sign), arachnoid cysts, soft tissue masses in the subarachnoid space, and/or failure of nerve roots to migrate ventrally on prone MR/Myelo-CT studies. METHODS/UNASSIGNED:We reviewed 3 articles and 7 clinical series that involved a total of 253 patients with AA/CAA to determine whether there was a significant correlation between these clinical syndromes, and myelographic, Myelo-CT, and/or MR imaging pathology. RESULTS/UNASSIGNED:We determined that patients with the clinical diagnoses of AA/CAA do not necessarily exhibit associated radiographic abnormalities. However, a subset of patients with AA/CAA may show the classical AA/CAA findings of; central or peripheral nerve root/cauda equina thickening/clumping (empty sac sign), arachnoid cysts, soft tissue masses in the subarachnoid space, and/or failure of nerve roots to migrate ventrally on prone MR/ Myelo-CT studies. CONCLUSION/UNASSIGNED:Patients with clinical diagnoses of AA/CAA do not necessary show associated neuroradiagnostic abnormalities on myelograms, Myelo-CT studies, or MR. Rather, the clinical syndromes of AA/CAA may exist alone without the requirement for radiolographic confirmation.

BACKGROUND:Late-Onset Tay-Sachs (LOTS) disease is a rare, progressive neurological condition that can dramatically affect the life of these patients. The diagnosis of LOTS is easily missed because of the multifaced presentation of these patients, who can initially be assessed by neuromuscular or movement disorder specialists, or psychiatrists. Clinical trials are now becoming available for LOTS. Therefore, early diagnosis can be detrimental for these patients and for insuring informative research outcomes. METHODS:We characterized a cohort of nine patients with LOTS through a detailed clinical and video description. We then reviewed the available literature regarding the clinical description of patients with LOTS. Our findings were summarized based on the predominant phenotype of presentation to highlight diagnostic clues to guide the diagnosis of LOTS for different neurology specialists (neuromuscular, movement disorders) and psychiatrist. RESULTS:We described a cohort of 9 new patients with LOTS seen at our clinic. Our literature review identified 76 patients mainly presenting with a neuromuscular, cerebellar, psychiatric, stuttering, or movement disorder phenotype. Diagnostic tips, such as the triceps sign, distinct speech patterns, early psychiatric presentation and impulsivity, as well as neurological symptoms (cerebellar or neuromuscular) in patients with a prominent psychiatric presentation, are described. DISCUSSION:Specific diagnostics clues can help neurologists and psychiatrists in the early diagnosis of LOTS disease. Our work also represent the first video presentation of a cohort of patients with LOTS that can help different specialists to familiarize with these features and improve diagnostic outcomes. HIGHLIGHTS:Late-Onset Tay-Sachs (LOTS) disease, a severe progressive neurological condition, has multifaced presentations causing diagnostic delays that can significantly affect research outcomes now that clinical trials are available. We highlight useful diagnostic clues from our cohort (including the first video representation of a LOTS cohort) and comprehensive literature review.

Importance/UNASSIGNED:Non-communicable chronic diseases (NCDs) such as obesity, type 2 diabetes, heart disease, and cancer were rare among non-western populations with traditional diets and lifestyles. As populations transitioned toward industrialized diets and lifestyles, NCDs developed. Objective/UNASSIGNED:We performed a systematic literature review to examine the effects of diet and lifestyle transitions on NCDs. Evidence Review/UNASSIGNED:We identified 22 populations that underwent a nutrition transition, eleven of which had sufficient data. Of these, we chose four populations with diverse geographies, diets and lifestyles who underwent a dietary and lifestyle transition and explored the relationship between dietary changes and health outcomes. We excluded populations with features overlapping with selected populations or with complicating factors such as inadequate data, subgroups, and different study methodologies over different periods. The selected populations were Yemenite Jews, Tokelauans, Tanushimaru Japanese, and Maasai. We also review transition data from seven excluded populations (Pima, Navajo, Aboriginal Australians, South African Natal Indians and Zulu speakers, Inuit, and Hadza) to assess for bias. Findings/UNASSIGNED:The three groups that replaced saturated fats (SFA) from animal (Yemenite Jews, Maasai) or plants (Tokelau) with refined carbohydrates had negative health outcomes (e.g., increased obesity, diabetes, heart disease). Yemenites reduced SFA consumption by >40% post-transition but men's BMI increased 19% and diabetes increased ~40-fold. Tokelauans reduced fat, dramatically reduced SFA, and increased sugar intake: obesity and diabetes rose. The Tanushimaruans transitioned to more fats and less carbohydrates and used more anti-hypertensive medications; stroke and breast cancer declined while heart disease was stable. The Maasai transitioned to lower fat, SFA and higher carbohydrates and had increased BMI and diabetes. Similar patterns were observed in the seven other populations. Conclusion/UNASSIGNED:The nutrient category most strongly associated with negative health outcomes - especially obesity and diabetes - was sugar (increased 600-650% in Yemenite Jews and Tokelauans) and refined carbohydrates (among Maasai, total carbohydrates increased 39% in men and 362% in women), while increased calories was less strongly associated with these disorders. Across 11 populations, NCDs were associated with increased refined carbohydrates more than increased calories, reduced activity or other factors, but cannot be attributed to SFA or total fat consumption.

Stroke rehabilitation seeks to accelerate motor recovery by training functional activities, but may have minimal impact because of insufficient training doses. In animals, training hundreds of functional motions in the first weeks after stroke can substantially boost upper extremity recovery. The optimal quantity of functional motions to boost recovery in humans is currently unknown, however, because no practical tools exist to measure them during rehabilitation training. Here, we present PrimSeq, a pipeline to classify and count functional motions trained in stroke rehabilitation. Our approach integrates wearable sensors to capture upper-body motion, a deep learning model to predict motion sequences, and an algorithm to tally motions. The trained model accurately decomposes rehabilitation activities into elemental functional motions, outperforming competitive machine learning methods. PrimSeq furthermore quantifies these motions at a fraction of the time and labor costs of human experts. We demonstrate the capabilities of PrimSeq in previously unseen stroke patients with a range of upper extremity motor impairment. We expect that our methodological advances will support the rigorous measurement required for quantitative dosing trials in stroke rehabilitation.

Studies of epilepsy patients provide insight into the neuroscience of human memory. Patients with remote memory deficits may learn new information but have difficulty recalling events from years past. The processes underlying remote memory impairment are unclear and likely result from the interaction of multiple factors, including hippocampal dysfunction. The hippocampus likely has a continued role in remote semantic and episodic memory storage over time, and patients with mesial temporal lobe epilepsy (TLE) are at particular risk for deficits. Studies have focused on lateralization of remote memory, often with greater impairment in left TLE, which may relate to verbal task demands. Remote memory testing is restricted by methodological limitations. As a result, deficits have been difficult to measure. This review of remote memory focuses on evidence for its underlying neurobiology, theoretical implications for hippocampal function, and methodological difficulties that complicate testing in epilepsy patients.