Background: Saccade and pupil responses are potential neurodegenerative disease biomarkers due to overlap between oculomotor circuitry and disease-affected areas. Instruction-based tasks have previously been examined as biomarker sources, but are arduous for patients with limited cognitive abilities; additionally, few studies have evaluated multiple neurodegenerative pathologies concurrently. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with Alzheimer’s disease (AD), mild cognitive impairment (MCI), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, progressive supranuclear palsy, or Parkinson’s disease (PD). Patients (n=274, age 40-86) and healthy controls (n=101, age 55-86) viewed 10 minutes of frequently changing video clips without instruction while their eyes were tracked. We evaluated differences in saccade and pupil parameters (e.g. saccade frequency and amplitude, pupil size, responses to clip changes) between groups. Results: Preliminary data indicates low-level behavioural alterations in multiple disease cohorts: increased centre bias, lower overall saccade rate and reduced saccade amplitude. After clip changes, patient groups generally demonstrated lower saccade rate but higher microsaccade rate following clip change to varying degrees. Additionally, pupil responses were blunted (AD, MCI, ALS) or exaggerated (PD). Conclusions: This task may generate behavioural biomarkers even in cognitively impaired populations. Future work should explore the possible effects of factors such as medication and disease stage.

Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.

Background: To determine whether exosomal microRNAs (miRNAs) in CSF of patients with FTD can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic FTD Initiative (GENFI) cohort and in sporadic FTD. Methods: GENFI participants were either carriers of a pathogenic mutation or at risk of carrying a mutation because a first-degree relative was a symptomatic mutation carrier. Exosomes were isolated from CSF of 23 -pre-symptomatic and 15 symptomatic mutation carriers, and 11 healthy non-mutation carriers. Expression of miRNAs was measured using qPCR arrays. MiRNAs differentially expressed in symptomatic compared to pre-symptomatic mutation carriers were evaluated in 17 patients with sporadic FTD, 13 patients with sporadic Alzheimer’s disease (AD), and 10 healthy controls (HCs). Results: In the GENFI cohort, miR-204-5p and miR-632 were significantly decreased in symptomatic compared to pre-symptomatic mutation carriers. Decrease of miR-204-5p and miR-632 revealed receiver operator characteristics with an area of 0.89 [90% CI: 0.79-0.98] and 0.81 [90% CI: 0.68-0.93], and when combined an area of 0.93 [90% CI: 0.87-0.99]. In sporadic FTD, only miR-632 was significantly decreased compared to sporadic AD and HCs. Decrease of miR-632 revealed an area of 0.89 [90% CI: 0.80-0.98]. Conclusions: Exosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD.

Background: Post concussion syndrome (PCS) can affect up to 30% of patients with concussion. Biomarkers of this condition would be beneficial for diagnosis and management. We hypothesized that eye tracking parameters would correlate with microstructural changes of white matter integrity, as measured by diffusion tensor imaging (DTI), in patients with PCS. Methods: Sixty patients with PCS and at least 2 concussions participated in our prospective study. Attention and executive function were tested using Visual Attention Scanning Technology (VAST). In a matching task, the normalized number of visits to master image before making the first selection is used as a surrogate of working memory. We related performance on VAST to white matter integrity using Tract-Based Spatial Statistics of diffusion tensor imaging data. Results: 60 participants (mean age 34.3 years, SD 13.8) had a mean of 4 concussions. There were negative correlations between fractional anisotropy (FA) of the genu, body, and splenium of the corpus callosum and normalized number of visits to master image before first selection (r=-0.432, p=0.001; r=-0.504, p<0.001; and r=-0.388, p=0.002; respectively). A negative correlation was also seen between right cingulum FA and the global processing index (r=-0.349, p=0.006). Conclusions: Impaired performance on eye tracking measures of attention and executive function may reflect alterations in white matter tracts.

Background: Most individuals recover from a concussion within 7-10 days. However recovery may be very prolonged. Individuals who do not recover within the usual time are said to have postconcussion syndrome (PCS). The objective of this study was to examine the demography and predictors of PCS. Methods: This was a retrospective cohort study of 284 consecutive concussed patients 221 of whom had PCS on the basis of at least three symptoms persisting at least 1 month. A uniform, internationally accepted definition of concussion was used. Results: The 221 cases showed considerable heterogeneity in clinical features of PCS. They averaged 3.3 concussions with a range of 0 to 12+ concussions, and 62.4% occurred during sports and recreation. The median duration of PCS was 7 months at the time of examination, with 11.8% lasting more than 2 years. Surprisingly, 23.1% with PCS had only 1 concussion. The average age was 27 years (range 10-74). The average number of persistent symptoms was 8.1. 26.2% had a previous psychiatric condition, ADD/ADHD, a learning disability, or previous migraine headaches. The prevalence of arachnoid cysts and Chiari malformation in PCS exceeded the general population. Conclusions: In most of our cases, PCS was disabling, and lasted for months or years.

A 40-year old female presented to the emergency room at London Health Sciences Centre with a one week history of gradually progressive right leg weakness which had caused several falls. She also described numbness of the right arm and leg. In the two weeks leading up to admission she experienced gradually worsening shortness of breath, fatigue, anorexia, confusion, night sweats and somnolence. She also developed a herpetic rash of the right upper thigh which was treated with acyclovir and gabapentin.

Her past medical history was significant for a diagnosis of systemic lupus erythematosis (SLE) for seven years, treated at the time of admission with azathioprine 50 mg TID (several years duration), prednisone 5 mg BID, and hydroxyquine 400 mg daily. She also had a history of asthma and occasionally required Ventolin treatment. She had a 25 pack-year smoking history.

AlGaAs/InGaAs/GaAs heteroepitaxial layers grown by molecular beam epitaxy were studied by cross-sectional transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS). The presence of waviness/roughness, fine periodic striation contrast due to Al composition oscillations, and defects were observed by TEM in selected samples. EDS on the TEM was of limited utility in determining the composition of thin epitaxial layers and in comparing the composition near and away from a defect. Arguments are presented to rationalize these results.