Survivors of adolescent and young adult (AYA) central nervous system (CNS) neoplasms are at risk for late effects (LE) - treatment-related health problems occurring more than 5 years after therapy). Since, in Canada, AYA survivors are usually followed in the community, information must be conveyed to primary care providers to guide risk-based follow-up care. Objective: To assess documentation of LE risks and screening recommendations (SR) in medical records of AYA CNS tumor survivors treated with radiation therapy. Methods: The medical records of all patients diagnosed with a CNS neoplasm (benign or malignant) at ages 15-39 years, treated between 1985 and 2010 in the province of British Columbia, surviving >5 years and discharged to the community were assessed. Documentation of LE and SR were extracted, and analyzed descriptively. Results: Among 132 survivors (52% female), treated with radiation therapy (95% partial brain, 10% craniospinal, 8% partial spine, and 4% whole brain) and chemotherapy (17%), 19% of charts included no documentation of LE risks, 26% included only non-specific documentation, and 55% had minimal documentation (1 or 2 LE). Documentation of at least one specific LE increased from 24% in 1980-1989, to 54% in 1990-1999, to 86% in 2000 – 2010. Based on treatment information, all survivors were at high-risk for LE, such as radiation induced neoplasm, meningioma and cerebrovascular events. Yet, SR were documented in only 25% of charts. Conclusions: The documentation of LE risks and screening recommendations has been limited, highlighting the need to improve written communication with primary care providers.

The Canadian Association of Neuropathologists (CANP) held their 57th annual meeting at the Inn at the Forks Hotel in Winnipeg, Manitoba from October 12th-14th, 2017, under the leadership of Dr. Marc Del Bigio, CANP president, who also handled the local arrangements. The annual banquet was held at the Assiniboine Park Conservancy where the polar bears captivated the crowd of Neuropathologists.

The academic program of 14 scientific abstracts and 11 unknown cases were compiled by the CANP Secretary-Treasurer Dr. Julia Keith into 4 sessions; Infectious/Immune Mediated and Epilepsy Neuropathology, Tumour Neuropathology, Developmental Neuropathology and Neurodegenerative/Neuromuscular Neuropathology. The program also included a guided interactive forum on Quality Assurance and Professional Affairs for Neuropathologists led by Dr Del Bigio.

The digital pathology images from the 11 unknown cases are available for viewing online (www.canp.ca) thanks to the CANP webmaster, Dr. Jason Karamchandani. All submitted abstracts were peer reviewed by the CANP Abstract Review committee comprised of Drs. Marie-Christine Guiot, David Munoz, and Harvey Sarnat.

The Presidential Symposium explored the theme of Pediatric Head Injuries and Forensic Neuropathology. Dr. Michael J. Ellis (Section of Neurosurgery, University of Manitoba) delivered an invited lecture entitled Current Concepts in Pediatric Concussion. The Dr. Gordon Mathieson invited member lecturer was Dr. David Ramsay (Western University) who spoke on the subject of Observations on Selected Neuropathological Aspects of Suspected Inflicted Head and Spinal Injury in Young Children. The Dr. David Robertson invited lecture was delivered by Dr. Paul Kadar (Department of Pediatrics, Hospital for Sick Children, University of Toronto) Child Maltreatment/Abusive Head Trauma in a “Pre-” and “Post-Goudge” World. The Dr. Jerzy Olszewski guest lecturer was Dr. Waney Squier (Oxford University, UK) who explained the Impact of Legal Changes in the UK on Brain Retention, Evolving Opinions and Controversies about “Shaken Baby Syndrome”. The symposium concluded with a panel discussion and group Question and Answer session with the symposium speakers.

The resident awards committee was comprised of Drs. Sidney Croul and Sherry Krawitz. The Mary Tom Award for best clinical science paper was awarded to Dr. Randy van Ommeren (supervisor Dr. Patrick Shannon) for his presentation of Unknown Case #8 and the Morrison H. Finlayson Award went to Dr. Andrew Gao (supervisor Dr. Lili Hazrati) for his presentation Abstract #14 The Role of ATP and P2X Purinoreceptor 7 in the Pathogenesis of Cerebral Tau.

The following abstracts were presented at the 2017 Canadian Association of Neuropathologists (CANP) 57th Annual Meeting in October. The material presented contains the abstracts submitted as part of the 2017 Canadian Association of Neuropathologists (CANP) 57th Annual Meeting, as part of the standard processes of The Canadian Journal of Neurological Sciences, and may contain promotional content that does not represent the views or policies of the journal or publisher. The content and the views expressed therein are those of the presenting entity and not the Editors of The Canadian Journal of Neurological Sciences, the Canadian Neurological Sciences Federation, or Cambridge University Press. Authors have not provided standard disclosure forms as part of their submission, although these would have been evident at the time of the meeting.

Advances in high-resolution ultrasound have provided clinicians with unique opportunities to study diseases of the peripheral nervous system. Ultrasound complements the clinical and electrophysiology exam by showing the degree of abnormalities in myopathies, as well as spontaneous muscle activities in motor neuron diseases and other disorders. In experienced hands, ultrasound is more sensitive than MRI in detecting peripheral nerve pathologies. It can also guide needle placement for electromyography exam, therapeutic injections, and muscle biopsy. Ultrasound enhances the ability to detect carpal tunnel syndrome and other focal nerve entrapment, as well as pathological nerve enlargements in genetic and acquired neuropathies. Furthermore, ultrasound can potentially be used as a biomarker for muscular dystrophy and spinal muscular atrophy. The combination of electromyography and ultrasound can increase the diagnostic certainty of amyotrophic lateral sclerosis, aid in the localization of brachial plexus or peripheral nerve trauma and allow for surveillance of nerve tumor progression in neurofibromatosis. Potential limitations of ultrasound include an inability to image deeper structures, with lower sensitivities in detecting neuromuscular diseases in young children and those with mitochondrial myopathies, due to subtle changes or early phase of the disease. As well, its utility in detecting critical illness neuromyopathy remains unclear. This review will focus on the clinical applications of neuromuscular ultrasound. The diagnostic values of ultrasound for screening of myopathies, neuropathies, and motor neuron diseases will be presented.

Organic mercury, especially methylmercury, poisoning causes chronic neurological disease predominantly affecting the brain. There have been documented exposures from eating fish from contaminated waters in Japan and in northwestern Ontario and in Iraq from eating bread made from seed wheat treated with methylmercuric fungicide. The neurological disease is called Minamata disease in Japan. Visual field constriction due to involvement of the calcarine cortex, sensory disturbance due to involvement of the somatosensory cortex, and cerebellar ataxia due to involvement of granule cell neurons of the cerebellum are common and characteristic features due to methylmercury poisoning. Other neurological features include dysarthria, postural and action tremor, cognitive impairment, and hearing loss and dysequilibrium. In contrast, peripheral nerve disease is more characteristic of inorganic mercury intoxication. Similarly, psychosis is more typical of exposure to inorganic mercury, which has been documented in the felt hat industry (“mad hatter”). Laboratory tests (e.g., on blood and hair and toenail samples) are of limited value in the assessment of chronic neurological disease due to mercury poisoning because they may not reflect remote neuronal injury due to mercury. Methylmercury also causes injury to fetal brains during development. There is no effective treatment.

Recent therapeutic advances in the management of multiple sclerosis (MS) have raised questions about the selection of appropriate patient candidates for various treatments and, if the plan is to move from one treatment to another, the appropriate sequencing of these therapies. The selected approach should provide optimal disease management without limiting future therapeutic options based on safety concerns, and recognize potential future treatments and the possibility of combination therapies. Additional challenges include incorporation of patient needs and preferences into the overall therapeutic approach, in order to ensure optimal outcomes in the short and long term. The objective of this manuscript is to provide an overview of what is currently known regarding the impact of various therapies for MS on future therapeutic choices (sequencing). In this context, we reviewed the available evidence in support of various treatments and, based on the presence of disease activity, suggested a scheme for switching or escalating therapy with the main focus on sequencing of therapeutic approaches.

PURPOSE: To investigate health-related quality of life (HRQOL ) in survivors of intracranial germ cell tumors (IGCT). METHODS: Survivors of IGCT were invited to complete the 36-Item Short Form Survey Instrument (SF-36). The SF-36 is scored from 0-100, with a higher number representing a more favorable HRQOL. RESULTS: The study cohort consisted of 12 survivors of IGCT, 6 males and 6 females. Median age was 13 years at diagnosis, and 26 years at time of study. Median follow-up was 11 years. Five patients had germinomas, and 7 had non-germinomatous germ cell tumors. All 12 patients received radiation therapy (RT), 10 to the craniospinal axis, 1 to the whole ventricles and 1 to the tumor bed alone. Nine patients received chemotherapy. Mean SF-36 scores were 67.9 (standard deviation [SD] 33.2) for physical functioning, 58.3 (SD 37.4) for role limitations due to physical health, 77.8 (SD 32.8) for role limitations due to emotional problems, 43.1 (SD 18.4) for vitality, 74.3 (SD 15.3) for mental health; 62.5 (SD 32.0) for social functioning, 74.2 (SD 33.4) for pain, and 57.1 (SD 24.0) for general health; mean scores were >1 SD lower than that of Canadian normative data for vitality, social functioning and general health. Physical component score was 43.6 (SD 13.9) and mental component score was 47.6 (SD 11.2), normalized to a US population with mean of 50 and SD of 10. CONCLUSIONS: Long-term HRQOL for survivors of IGCT is lower than that of the overall population, particularly in vitality, social functioning and general health.

Background: The widely accepted treatment for idiopathic normal-pressure hydrocephalus (iNPH) is a cerebrospinal fluid (CSF) diversion shunt procedure, to which approximately 80% of patients will respond. The purpose of this systematic review was to identify which CSF biomarkers have been investigated in predicting shunt responsiveness in iNPH patients, and to analyze the level of evidence for each. Methods: To find all relevant articles, a comprehensive search of Medline, Embase, and PsycINFO was conducted. Results: The literature search identified 344 unique citations, of which 13 studies satisfied the inclusion criteria and were analyzed in our review. These 13 studies reported on 37 unique biomarkers. Conclusions: The available studies suggest that there is evidence for the utility of CSF biomarkers in predicting shunt responsiveness in iNPH patients, though none have been shown to predict shunt response with both high sensitivity and specificity. We found that there is no available evidence for the use of Aβ38, Aβ40, Aβ43, APL1β25, APL1β27, APL1β28, sAPP, aAPPα, sAPPβ, TNF-α, MCP-1, sCD40L, sulfatide, MBP, L-PGDS, cystatin C, transthyretin, TGF-β2, or YKL-40 in predicting shunt response. There is minimal evidence for the use of TGF-β1, TBR-II, homocysteine, and interleukins (particularly IL-1β, IL-6, and IL-10). However, the available evidence suggests that these biomarkers warrant further investigation. Aβ42, tau, p-tau, NFL, and LRG have the greatest amount of evidence for their predictive value in determining shunt responsiveness in iNPH patients. Future research should be guided by, but not limited to, these biomarkers.

The purpose of this review is to provide an update of the research regarding the etiology, diagnosis and management of psychogenic non-epileptic seizures (PNES). A literature search using Pubmed, Ovid MEDLINE and EMBASE database was performed from 2000 up to August 2017. We have evaluated the different factors leading to PNES as well as the diagnostic approach and management of this disorder which continue to be very difficult. The coexistence of epilepsy and PNES poses special challenges and requires the coordinated efforts of the family physicians, psychiatrists, psychologists and neurologists. Although this condition has an overall poor prognosis, a multidisciplinary approach in the diagnosis and management of this disorder would likely improve the outcomes. We have proposed a diagnostic and treatment algorithm for PNES and suggested a national registry of patients suffering from this condition. The registry would contain data regarding treatment and outcomes to aid in the understanding of this entity.

SVcPACNS is a rare inflammatory/immune disorder that typically affects the small blood vessels of the brain. SVcPACNS differs from most adult forms of PACNS by being predominantly lymphocytic, non-granulomatous and non-necrotizing. Previously healthy children are typically affected by range of signs and symptoms, including: seizures, headache, cognitive decline, behavior/personality change, focal neurological deficits and potentially a decreased level of consciousness. Treatment protocols featuring induction (steroids and cyclophosphamide) and subsequent maintenance phases (e.g., mycophenolate mofetil) have been demonstrated to yield favorable outcomes. Since SVcPACNS is characteristically angiography negative, the diagnostic gold standard is brain biopsy. Interpretation of these biopsies is often challenging given the histologic overlap between SVcPACNS and encephalitis. Distinguishing the foregoing is critical since the treatment of these entities is significantly different.

Herein, a rare autopsy case of SVcPACNS in a 4 year old male is presented. This case provides a unique opportunity to review the Alrawi criteria for the histologic diagnosis of PACNS and establish/refine criteria specific to SVcPACNS. Generally, such criteria should feature: 1) an intramural and lymphocyte predominant infiltrate devoid of multinucleated giant cells; 2) structural vessel alterations lacking fibrinoid necrosis; 3) perivascular pathology supportive of an angiocentric process; 4) the absence of encephalitis; and, 5) the absence of a concurrent systemic or rheumatic illness that could account for the CNS findings.

Background: Carotid atherosclerosis is a significant risk factor for stroke and has been associated with cognitive decline and dementia. Methods: We assessed 554 community-dwelling subjects from the Lothian Birth Cohort of 1936 (LBC1936) who underwent brain MRI and carotid Doppler ultrasound studies at age 73 years. The relationship between carotid stenosis and cerebral cortical thickness was examined cross-sectionally, controlling for gender, extensive vascular risk factors (VRFs), and IQ at age 11 (IQ-11). The association between carotid stenosis and a composite measure of fluid intelligence was also investigated. Results: A widespread negative association was identified between carotid stenosis and cerebral cortical thickness at age 73 years, independent of the side of carotid stenosis, other carotid measures, VRFs, or IQ-11. This association increased in an almost dose-response relationship from mild to severe degrees of carotid stenosis. A negative association was also noted between carotid stenosis and fluid intelligence, which appeared partly mediated by carotid stenosis-related thinning of the cerebral cortex. Conclusions: Carotid stenosis is associated with thinner cerebral cortex and lower fluid cognitive abilities at age 73. The findings suggest that carotid stenosis represents a marker of vascular processes that accelerate cortical aging with a negative impact on cognition, independent of measurable VRFs.

Background Survival estimates are integral to care for patients diagnosed with dementia. Few Canadian studies have carried out long-term follow-up of well-described cohorts, analyzing survival related to multiple risk factors. Methods Survival analysis of an inception cohort enrolled at a British Columbia (BC) tertiary dementia referral clinic between 1997 and 1999 was undertaken. Vital status was completed for 168 patients diagnosed with dementia. An evaluation of the effects of demographics, vascular risk factors, cognitive and functional ratings, apolipoprotein 4-status, and cholinesterase use on survival was performed using a log-rank test and time-dependent Cox regression. Survival of this dementia cohort was compared with the age-matched life expectancy of persons in BC. Results In all, 158/168 (94.0%) subjects died over 16.6 years, with a median survival of 7.08 years. Risk factors associated with shorter survival in dementia groups included age of onset ≥80 (hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.05-2.32); greater functional disability (Disability Assessment for Dementia<55% [HR 1.47, 95% CI 1.04-2.08]); and cumulative medical illness severity (Cumulative Illness Rating Scale≥7 [HR 1.51, 95% CI 1.08-2.12)]. Compared with the BC population, years of potential life lost for dementia subjects aged <65 was 15.36 years, and for dementia subjects aged ≥80 it was 1.82 years. Conclusions Survival in dementia subjects is shorter than population life expectancies for each age strata, with greatest impact on younger patients. For people diagnosed with dementia, age ≥80 years, cumulative medical illness severity, and functional disabilities are the most significant survival predictors and can be used to guide prognosis.

Background: Neuromuscular disorders are a phenotypically and genotypically diverse group of diseases that can be difficult to diagnose accurately because of overlapping clinical features and nonspecific muscle pathology. Next-generation sequencing (NGS) is a high-throughput technology that can be used as a more time- and cost-effective tool for identifying molecular diagnoses for complex genetic conditions, such as neuromuscular disorders. Methods: One hundred and sixty-nine patients referred to a Canadian neuromuscular clinic for evaluation of possible muscle disease were screened with an NGS panel of muscular dystrophy–associated genes. Patients were categorized by the reason of referral (1) muscle weakness (n=135), (2) recurrent episodes of rhabdomyolysis (n=18), or (3) idiopathic hyperCKemia (n=16). Results: Pathogenic and likely pathogenic variants were identified in 36.09% of patients (61/169). The detection rate was 37.04% (50/135) in patients with muscle weakness, 33.33% (6/18) with rhabdomyolysis, and 31.25% (5/16) in those with idiopathic hyperCKemia. Conclusions: This study shows that NGS can be a useful tool in the molecular workup of patients seen in a neuromuscular clinic. Evaluating the utility of large panels of a muscle disease-specific NGS panel to investigate the genetic susceptibilities of rhabdomyolysis and/or idiopathic hyperCKemia is a relatively new field. Twenty-eight of the pathogenic and likely pathogenic variants reported here are novel and have not previously been associated with disease.

The classification system for gliomas has undergone significant revisions in the last several years, with the incorporation of molecular criteria and removal of mixed histologic diagnoses. Large-scale molecular studies have elucidated the biological characteristics of low grade gliomas, and enabled grouping based on IDH mutational and 1p19q codeletion status that outperforms histology in predicting patient outcomes. Mutations in ATRX and TP53 are largely mutually exclusive of 1p19q- codeletion in the context of mutant IDH, and are useful in screening patients for further molecular studies.

At our institution, new testing methods for 1p19q codeletion and ATRX were implemented in 2014, and in this presentation we review all cases submitted for 1p19q testing since this time. In comparing histologic to molecular diagnoses, the majority of histologic oligodendrogliomas indeed have 1p19q codeletion, while oligoastrocytomas and GBMOs largely are re-classified as astrocytomas and glioblastomas, respectively. We have also found that loss of ATRX nuclear expression associated with ATRX mutation is highly indicative of 1p19q retention, however the immunohistochemical test can be challenging to interpret and there have been a small number of discordant results.