Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.

Objective: Our aim was to assess the impact of jinxing on “call karma” in neurosurgery. Methods: We conducted a prospective observational study on 15 residents on call for the neurosurgery service, recording the total number of admissions, consults, deaths encountered, surgeries performed, hours of sleep and subjective call rating on a numeric rating scale (NRS) of 0-10 in terms of general awfulness. Results: Some 204 on-call nightshifts were analyzed, of which 61 (29.9%) were jinxed and 143 (70.1%) were nonjinxed. Jinxes seemed to occur in clusters. The baseline parameters (experience, type of call coverage and superstition level) of the study groups were well balanced. A trend toward more surgeries was observed during jinxed nights, where residents slept significantly less (mean 147.8±96.2 vs. 180.9±106.1 min, p=0.037) and rated their on-call experience worse on the NRS (4.4±2.2 vs. 3.5±2.0, p=0.011), while there was no significant difference in number of admissions, consults or deaths. Conclusions: The act of jinxing ought to be avoided in the neurosurgical setting, as it might be potentially harmful to resident call karma, irrespective of level of experience, resources and personal beliefs.

Background: ATP-sensitive K+ (KATP) channels couple metabolic state to cellular excitability. Activation of neuronal and astrocytic mitochondrial KATP (mitoKATP) channels regulates a variety of neuronal functions. However, less is known about the impact of mitoKATP on tonic γ-aminobutyric acid (GABA) inhibition. Tonic GABA inhibition is mediated by the binding of ambient GABA on extrasynaptic GABA A-type receptors (GABAARs) and is involved in regulating neuronal excitability. Methods: We determined the impact of activation of KATP channels with diazoxide (DIZ) on tonic inhibition and recorded tonic current from rat cortical layer 5 pyramidal cells by patch-clamp recordings. Results: We found that neonatal tonic current increased with an increase in GABA concentration, which was partially mediated by the GABA A-type receptor (GABAAR) α5, and likely the δ subunits. Activation of KATP channels resulted in decreased tonic current in newborns, but there was increased tonic current during the second postnatal week. Conclusions: These findings suggest that activation of KATP channels with DIZ regulates GABAergic transmission in neocortical pyramidal cells during development.

Background: Wearable activity trackers are an innovative tool for measuring sleep and physical activity. The Resident Activity Tracker Evaluation (RATE) is a prospective observational study evaluating the impact of work-hours, sleep, and physical activity on resident well-being, burnout, and job satisfaction. Methods: Residents were recruited from: 1. general surgery and orthopedics (SURG), 2. internal medicine and neurology (MED) and 3. anesthesia and radiology (RCD). Groups 1 and 2 do not enforce on-call duration restrictions and group 3 had 12-hour restricted-call durations (RCD). Participants wore FitBit activity trackers for 14 days and completed four validated surveys assessing self-reported health, sleepiness, burnout, and job satisfaction. Results: Fifty-nine residents completed the study. 778 days of activity and 244 on-call periods were tracked. Surgical residents worked 24 more hours per week than non-surgical residents (84.3 vs 60.7). Surgical residents had 7 less hours of sleep per week and reported significantly higher Epworth Sleepiness scores. Nearly two-thirds of participants (61%) scored high burnout on the Maslach depersonalization subscore. Total steps per day and self-reported well-being, burnout, and job satisfaction were comparable between the groups. Conclusions: Despite a positive correlation between work-hours and sleepiness, burnout and well-being were similar among residents. Physical activity did not prevent burnout. These findings are relevant to work-hours policies.

Background: Sepsis is a systemic response to infection that can affect brain function by inducing resident cells (including astrocytes and microglia) to generate brain chemokines and cytokines. However, there are few studies on the human brain. Since this information may shed further light on pathogenesis, our study objective was to measure the expression of 36 chemokines and cytokines in autopsied brain from 3 cases of sepsis and 10 controls, and to relate this to astrocyte and microglial activation. Methods: The right frontal pole was removed at autopsy and chemokine and cytokine expression measured by multiplexed enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (qPCR). Immunohistochemistry and image analysis were carried out to determine the expression of glial fibrillary acidic protein (GFAP), a marker of activated astrocytes, and CD68 and CD45, markers of activated microglial cells. Results: Concentrations of the chemokines CXCL8, CXCL10, CXCL12, CCL13 and CCL22 were increased in pooled data from the three cases of sepsis (p<0.05); however, their messenger RNA (mRNA) expression was unaltered. CXCL13, CXCL1, CXCL2, CCL1, CCL2, CCL8, CCL20, (interleukin) IL-16, IL-1β and (tumour necrosis factor) TNF concentrations showed increases in two of three sepsis cases. Additionally, individual sepsis cases showed increases in mRNA expression for HDAC (histone deacetylase) 6 and EIF (eukaryotic translation initiation factor) 4A2. Brain GFAP expression was significantly increased (p<0.05) in pooled data from the three sepsis cases. Individual sepsis cases showed increases in CD68 or CD45 expression. Conclusions: These expression patterns add to our understanding of the pathogenesis of sepsis and its effects on the brain.

Background: Individuals with Parkinson’s disease (PD) often present with visual symptoms (e.g., difficulty in reading, double vision) that can also be found in convergence insufficiency (CI). Our objective was to estimate the prevalence of CI-type visual symptomatology in individuals with PD, in comparison with controls. Methods: Participants ≥50 years with (n=300) and without (n=300) PD were recruited. They were administered the Convergence Insufficiency Symptom Survey (CISS–15) over the phone. A score of ≥21 on the CISS–15, considered positive for CI-type symptomatology, served as the cutoff. Data from individuals (n=87 with, n=94 without PD) who were approached but who reported having a known oculovisual condition were analysed separately. Student’s t test and chi-square at the 0.05 level were employed for statistical significance. Results: A total of 29.3% of participants with versus 7.3% without PD presented with a score of ≥21 on the CISS–15 (p=0.001). Of the participants having a known oculovisual condition, 39.1% with versus 19.1% without PD presented with a score of ≥21 on the CISS–15 (p=0.01). Conclusions: The prevalence of CI-type visual symptoms is higher in individuals with versus without PD whether or not they have a coexisting oculovisual condition. These results suggest that PD per se places individuals with the disease at greater risk of visual symptomatology. These results further underline the importance of providing regular eye exams for individuals with PD.

Background: Fluoroquinolones (FQs) are one of the most prescribed classes of antibiotics in North America. There have been a number of cases reports linkingn FQs with secondary pseudotumor cerebri syndrome (PTCS) but data from large epidemiological studies are lacking. Methods: We conducted a case-control study of people 15-60 years of age from the LifeLink Database (IMS, USA). Cases had the first international classification for disease 9th edition clinical modification (ICD-9 CM) code for benign intracranial hypertension (BIH) as well as having received a procedure code for an MRI or CT scan and a lumbar puncture within 15 days or 30 days of receiving the BIH code. For each case, ten controls were selected and matched to the cases by age, gender and calendar time. Results: From a cohort of 6,110,723 people, there were 339 cases of PTCS and 3,390 corresponding controls. In the primary analysis, the adjusted rate ratio (RR) for current users for fluoroquinolones for both the 15 day and 30 day definitions were 5.67 (95% CI:2.72-11.83) and 4.15 (95% CI:2.29-7.50) respectively. Conclusions: Our study suggests an increase in the risk of PTCS with current users of fluoroquinolones. Patients who experience symptoms of raised intracranial pressure including headaches and double vision when on FQs should seek medical attention.

Background: Myotonic dystrophy type 1 is an autosomal dominant condition affecting distal hand strength, energy, and cognition. Increasingly, patients and families are seeking information online. An online neuromuscular patient portal under development can help patients access resources and interact with each other regardless of location. It is unknown how individuals living with myotonic dystrophy interact with technology and whether barriers to access exist. We aimed to characterize technology use among participants with myotonic dystrophy and to determine whether there is interest in a patient portal. Methods: Surveys were mailed to 156 participants with myotonic dystrophy type 1 registered with the Canadian Neuromuscular Disease Registry. Results: Seventy-five participants (60% female) responded; almost half were younger than 46 years. Most (84%) used the internet; almost half of the responders (47%) used social media. The complexity and cost of technology were commonly cited reasons not to use technology. The majority of responders (76%) were interested in a myotonic dystrophy patient portal. Conclusions: Patients in a Canada-wide registry of myotonic dystrophy have access to and use technology such as computers and mobile phones. These patients expressed interest in a portal that would provide them with an opportunity to network with others with myotonic dystrophy and to access information about the disease.