Improving neurocognitive outcomes following treatment for brain metastases have become increasingly important. We propose that a brief telephone-based neurocognitive assessment may improve follow-up cognitive assessments in this palliative population. Aim: To prospectively assess the feasibility and reliability of a telephone based brief neurocognitive assessment compared to the same tests delivered face-to-face. Methods: Brain metastases patients to be treated with whole brain radiotherapy (WBRT) were assessed using a brief validated neurocognitive battery at baseline, at 1 month and 3 months following WBRT (in person and over the phone). The primary outcome was feasibility and inter-procedural (in person versus telephone) reliability. The secondary objective was to evaluate the change in neurocognitive function before and after WBRT. Results: Out of 39 patients enrolled, 82% of patients completed the baseline in-person and telephone neurocognitive assessments. However, at 1 month, only 41% of enrolled patients completed the in-person and telephone cognitive assessments and at 3 months, only 10% of patients completed them. Results pertaining to reliability and change in neurocognitive function will be updated. Conclusion: The pre-defined definition of feasibility (at least 80% completion for face to face and telephone neurocognitive assessments) was met at baseline. However, a large proportion of participants did not complete either telephone or in person neurocognitive follow-up at 1 month and at 3 months post-WBRT. Attrition remained a challenge for neurocognitive testing in this population even when a telephone-based brief assessment was used.

Dravet syndrome (DS) is a severe epilepsy syndrome characterized by early onset of multiple types of seizures. We report the first case of reflex seizures triggered by diaper change in a girl at 9 months old and 2 years old with a mutation in the SCN1A gene causing DS. Reflex seizures have been reported in patients with DS provoked by increased body temperature or visual stimulation. The case we report widens the spectrum of triggers causing reflex seizures in children with DS. Cortical hyperexcitability resulting from the genetic defect explains the tendency to experience such reflex seizures.

Prostate cancer is associated with vertebral metastasis in up to 10% of patients; however, intradural spinal cord metastases (ISCM) are much less frequent. We present the clinical and histopathological findings of a patient with ISCM arising from prostate. A PubMed literature search for ISCM from the prostate yielded a total of nine additional cases. ISCM of the prostate occurs at a late stage of systemic disease and the prognosis is generally poor. Decompressive surgery followed by adjuvant radiation therapy may help reduce intractable pain and stabilize neurological symptoms, thereby improving quality of life.

Background: NCSE dramatically increases morbidity and mortality. It is clinically subtle, which makes it difficult to diagnose without EEG. StatNet EEG provides a quick alternative to conventional EEG, which is often unavailable after hours. Methods: Each patient received a StatNet EEG by a neurology resident and a conventional EEG by an EEG technologist. Blinded studies were compared for delay between the studies, setup time, artifact, and abnormality detection using conventional EEG as controls. Nonparametric Mann-Whitney two-sample T-test was used. Results are expressed in mean minutes +/- SD. Kappa score assessed inter-observer reliability. Results: 19 patients were collected. Two StatNet EEGs were not interpretable and excluded. The mean delay between studies was 26h53min. Electrode placement is significantly shorter: 13:14±5:24 StatNet EEG vs 18:07±5:35 conventional EEG (p=0.02).

Conclusions: There is high inter-rater reliability between the conventional and StatNet EEG groups (table 1) demonstrating that StatNet is a reliable and effective tool, aiding in early recognition and management of NCSE.

Objectives: 1) Assess which electrodiagnostic studies Canadian clinicians use to aid in the diagnosis of carpal tunnel syndrome (CTS). 2) Assess whether Canadian clinicians follow the American Association of Neuromuscular & Electrodiagnostic Medicine/American Academy of Neurology/American Academy of Physical Medicine and Rehabilitation Practice Parameter for Electrodiagnostic Studies in CTS. 3) Assess how Canadian clinicians manage CTS once a diagnosis has been established. Methods: In this prospective observational study, an electronic survey was sent to all members of the Canadian Neuromuscular Group (CNMG) and the Canadian Association of Physical Medicine and Rehabilitation (CAPM&R) Neuromuscular Special Interest Group. Questions addressed which electrodiagnostic tests were being routinely used for the diagnosis of carpal tunnel syndrome. Management recommendations for CTS was also explored. Results: Of the 70 individuals who completed the survey, fourteen different nerve conduction study techniques were reported. Overall, 36/70 (51%) of participants followed the AANEM/AAN/AAPM&R Practice Parameter. The standard followed by the fewest of our respondents with 64% compliance (45/70) was the use of a standard distance of 13 to 14 cm with respect to the median sensory nerve conduction study. Regarding management, 99% would recommend splinting in the case of mild CTS. In moderate CTS, splinting was recommended by 91% of clinicians and 68% would also consider referral for surgery. In severe CTS, most recommended surgery (93%). Conclusions: There is considerable variability in terms of which electrodiagnostic tests Canadian clinicians perform for CTS. Canadian clinicians are encouraged to adhere to the AANEM/AAN/AAPM&R Practice Parameter for Electrodiagnostic Studies in CTS.

Due to the non-curative nature of high grade brain tumours “difficult discussions” about goals of care, advance care planning, palliative care, and end of life are inherent to the practice of the neuro-oncology team. Clinician and patient barriers are common and may include anxiety about destroying hope, lack of readiness to discuss end of life topics, difficulty managing emotional responses, and concerns over competency in facilitating difficult discussions. Nonetheless, clinician comfort and skill in facilitating these discussions is critical and can impact patient perception of illness, coping response, and ability to make decisions about care. Methods At our regional cancer centre, a novel quality improvement initiative was designed to bring monthly case presentation of “difficult discussions” into a pre-existing weekly multi-disciplinary case conference (MCC). We will describe the rationale and developmental processes behind this initiative. Roughly 15 neuro-oncology clinicians attended each case conference, with guest attendance from palliative care and psychosocial oncology. Clinician groups represented included physicians (77%), nurses (8%), nurse practitioners (10 %), and occupational therapists (5%). Baseline and monthly surveys were administered to determine clinicians’ self- rated practices, skills, and attitudes towards “difficult discussions”. Results Early findings indicate that the initiative has been well-received. Physicians indicated highest levels of agreement with the statement “I feel that having difficult discussions is part of my responsibility”. Non physician groups indicated the greatest agreement that the intervention is beneficial to their practice. Discussion: Our challenges and successes may help guide others to incorporate a similar initiative at disease-site meetings.

Background: Short- (SICI) and long-interval intracortical inhibition (LICI) are involved in the control of movement and movement initiation. Alterations to the two circuits can result in direct alterations to the physiology of the muscles and can be used to explain the physiological changes to individuals with spinal cord injury (SCI). Objective: To probe changes in GABAergic function by characterizing the recruitment curves of SICI and LICI interval intracortical inhibition in an upper limb muscle in chronic SCI participants with injury between C3 and C7. Methods: Recruitment curves were elicited with conditioning stimulus intensities determined as a percentage of active motor threshold (AMT) (SICI, 60% to 110% AMT; LICI, 90% to 130% AMT) and recorded from the flexor carpi radialis muscle during an isometric contraction equal to 15% to 20% of maximum voluntary contraction. Results: AMT was greater and motor-evoked potential sizes were lower in SCI compared with uninjured controls. SICI magnitude was not different between groups, although the range of conditioning stimulus intensities to evoke SICI was unique to each group. LICI was reduced in the control group during active contraction and remained present in SCI. Discussion: LICI was increased in the actively contracted flexor carpi radialis muscle in individuals with SCI compared with age-matched controls. These findings indicate that GABAB function mediating LICI is different in SCI versus controls. Conclusions: Increased LICI in SCI may be attributed to the medication baclofen or to changes in the neural mechanisms controlling contraction-related modulation of the LICI circuit.

Background: Leucine-rich glioma inactived-1 (LGI1) antibodies are associated with limbic encephalitis and distinctive seizure types, which are typically immunotherapy-responsive. While nonspecific EEG abnormalities are commonly seen, specific EEG characteristics are not currently understood to be useful for suspecting the clinical diagnosis. Based on initial observations in two patients, we analyzed the EEG recordings in a larger series of patients and describe a novel ictal pattern that can suggest the diagnosis of LGI1-antibody mediated encephalitis, even in the absence of common clinical features. Methods: Clinical and EEG data were collected in nine patients with LGI1 antibodies. Results: Psychiatric and cognitive symptoms were common, as were tonic seizures associated with EEG electrodecremental events (often with the so-called faciobrachial dystonic semiology). A rarity or absence of interictal epileptiform discharges contrasted with frequent subclinical temporal lobe seizures in some patients, which at times showed characteristics similar to subclinical rhythmic electrographic discharges of adults (SREDA), including sensitivity to hyperventilation. Conclusions: LGI1-antibody mediated encephalitis may be associated with tonic seizures and corresponding electrodecremental events, as well as an unusual SREDA-like pattern of frequent subclinical temporal lobe seizures, which may be triggered by hyperventilation, all in the setting of rare interictal epileptiform discharges.

Frontotemporal brain sagging syndrome is a dementia associated with hypersomnolence, personality changes, and features of intracranial hypotension on magnetic resonance imaging. The literature is sparse with respect to treatment options; many patients simply worsen. We present a case in which this syndrome responded to lumbar dural reduction surgery. Postoperative magnetic resonance imaging indicated normalization of brain sagging and lumbar intrathecal pressure. Although no evidence of cerebrospinal leak was found, extremely thin dura was noted intraoperatively, suggesting that a thin and incompetent dura could result in this low-pressure syndrome. Clinicians who encounter this syndrome should consider dural reduction surgery as a treatment strategy.

Individuals with primary brain tumors experience a range of physical, cognitive and psychosocial sequelae which impact their independence, safety and quality of life. These impairments may be addressed through rehabilitation intervention. Despite acknowledgement that timely rehabilitation services over the course of the disease process is of benefit, few outpatient neuro-oncology treatment teams include a rehabilitation professional. Purpose: The aims are: (1) to describe a rehabilitation consultation model of care integrated into outpatient neuro-oncology treatment for individuals with primary brain tumors; and (2) to describe the characteristics of individuals referred for rehabilitation services. Methods: This retrospective descriptive study examined data from 200 individuals that received rehabilitation consultation from January 2015 to March 2016 at Princess Margaret Hospital, Pencer Brain Tumor Centre. Information on patient demographics, referral characteristics, and number of patient care visits was collected. Descriptive statistics were calculated. Preliminary Results: Of all patients, (n=195), the most common diagnosis is glioblastoma, 39% (n=76), and 50% are 50-69 years of age (M=55, SD=15.0). The most common reason for initial referral was decline in physical functioning, strength and balance (41%). In 77% of cases, patients were seen immediately at the time of referral. In total, 540 consultations were completed (face-to-face=230, telephone=310) with 2.78 on average (SD=4.0) per patient. Conclusion: Given the range of symptoms that individuals with primary brain tumors experience coupled with changes in functional status as the disease progresses, integrated and timely rehabilitation consultation is feasible.

Born in Hanau, Germany, in 1614, Franciscus (Dele Boë) Sylvius received his medical doctor diploma from Basel University in 1637 and became Professor of Practical Medicine at Leiden University in 1658. One of the founders of medical biochemistry, Sylvius was also an outstanding anatomopathologist, with contributions ranging from the first description of the pulmonary tubercles to that of the lateral fissure of the brain. Thanks to Sylvius, a gifted teacher and one of the greatest physicians of his time, Leiden became a major European medical training center. He died in 1772 after having served as Rector Magnificus at Leiden University.

Background: Exploration of the insular cortex is now commonly considered in patients with refractory epilepsy requiring invasive EEG investigations. The safety and yield of routine insular exploration is uncertain. Methods: All patients (pediatric and adult) who had invasive EEG (iEEG) with insular depth electrode placement, either through SEEG or open implantation, were reviewed. Ictal insular involvement was characterized as primary, secondary or not involved. Results of insular resections were recorded. Results: A total of 173 patients had iEEG of which 26 included insular electrodes (SEEG-18, Open - 8). No complications of placement were identified. Insular involvement was seen in 20 (76%) patients. Primary ictal involvement was identified in 9 (33 %) patients, while secondary spread was noted in 11 (42 %) patients. Six patients went on to have resections including the insular cortex of which 5 patients achieved good seizure control (Engle class I/II). Conclusions: Insular depth electrode placement is a safe and effective adjunct to invasive EEG investigations. Ictal involvement of the insular cortex was commonly identified in our series leading to inclusion of the insula in cortical resections with good seizure control, which may not have been considered without iEEG evidence.

Human embryonic stem cells (hESCs) are known for their indefinite self-renewal ability and pluripotent nature. However, during long-term culture, normal hESCs can undergo neoplastic transformation and acquire enhanced self-renewal ability and aberrant differentiation potential. These transformed-hESCs (trans-hESCs) exhibit high expression of the pluripotent gene, LIN28A. LIN28A, an RNA binding protein, is known: for its role in self-renewal of hESCs, as a reprogramming factor for generating induced-pluripotent stem cells and as a potent oncogene in several poorly differentiated, highly malignant human cancers. Despite its multiple functions, how LIN28A contributes to neoplastic transformation of normal hESCs is poorly understood. Our preliminary data demonstrate that following LIN28A knockdown, trans-hESCs display normal hESCs morphology consisting of both pluripotent colony cells surrounded by more differentiated fibroblast-like cells. Neural precursors derived from LIN28A knockdown trans-hESCs also revert back to a state of normal cell morphology and growth. Further analyses revealed that the expression levels of stage-specific embryonic antigen (SSEA3), OCT3/4 and NANOG decreases and are comparable to that observed in normal hESCs following LIN28A downregulation. Expression of miRNA targets of LIN28A such as let7i and mir125b was increased to levels seen in normal hESCs. These preliminary results indicate that LIN28A is a major contributing factor to neoplastic transformation of hESCs and that this process can be reversed by cellular “reprogramming”. This study will enhance our understanding of role of LIN28A in the transformation process in various human cancers thus, underscoring the value of hESCs and their neoplastic-derivatives as cellular and molecular model for studying tumor progression.

Medulloblastoma (MB), the most common malignant pediatric brain tumor, is categorized into four molecular subgroups. Given the high rate of metastatic dissemination at diagnosis and recurrence in Group 3 MBs, these patients have the worst clinical outcome with a 5-year survivorship of approximately 50%. By adapting the existing COG (Children’s Oncology Group) Protocol for children with newly diagnosed high-risk MB, for treatment of immuno-deficient mice intracranially engrafted with human MB brain tumour initiating cells we aim to identify and characterize the treatment-refractory cell population in Group 3 MBs. Mice were sacrificed at multiple time points during the course of tumor development and therapy: (i) at engraftment; (ii) post-radiation; (iii) post-radiation and chemotherapy; and (iv) at MB recurrence. MB cell populations recovered separately from brains and spines were comprehensively profiled for gene expression analysis, stem cell and molecular features to generate a global, comparative profile of MB cells through therapy. We report a higher expression of CD133, Sox2 and Bmi1 in addition to increased self-renewal capacity following chemoradiotherapy treatment. The enrichment map constructed from global gene expression analysis showed an increase in pathways regulating self-renewal, DNA repair and chemoresistance post-therapy despite the apparent decrease in tumour size and vascularity. Additionally, from gene expression at MB recurrence, we identified a list of genes that negatively correlate with survival in patients diagnosed with Group 3 MB. A differential genomic profile of the “treatment-responsive” tumors against those that fail therapy may contribute to discovery of novel therapeutic approaches for the most aggressive subgroup of MB.

Background: There are currently no national standards for clinical electromyography (EMG) training for residents in neurology and physiatry in Canada. The purpose of this study was to obtain demographic and qualitative data pertaining to EMG residency training in Canada, with the goal of facilitating discourse that could lead to national standards for EMG training. Methods: An online survey was distributed to senior neurology and physiatry residents (post-graduate years 3-5), at seven tertiary Canadian centres. The study authors, who are trainees and consultants with a broad range of EMG expertise (junior and senior resident, clinical neuromuscular fellows, senior physiatrist and neuromuscular neurologists), developed pertinent demographic and qualitative questions. Results: Thirty-eight residents completed the survey (23 neurology, 15 physiatry). There was inter-program variation in quantity of the training experience, content of the curriculum, access to expertise (including technologists) and goals for future training and practice. Similarly, differences were identified between the training experiences of neurology and physiatry residents. Conclusions: Inter-program variability in EMG training was identified. Additionally, differences were identified between neurology and physiatry resident training. This data provides evidence of training discrepancies across the country and can be used to establish national training standards for EMG in Canada.