The Canadian Association of Neuropathologist – L’ Association Canadienne de Neuropathologistes (CANP-ACNP) held their 59th annual meeting at the Delta Kingston Waterfront from October 23rd to 26th, 2019, under the leadership of Dr. Peter Gould, President of the CANP-ACNP, Dr. Julia Keith, Secretary Treasurer of the CANP-ACNP, and Dr. John Rossiter, local organizer. The annual banquet was held at River Mill Restaurant in Kingston.

The academic program comprised 14 Abstracts, 14 unknown cases, a Symposium on Neurodegenerative Neuropathology, and a Neuropathology Practice lecture by Dr. Gerard Jansen entitled CJD, CJD Surveillance, and Occupational Risk. Can worms ever be re-canned? The interactive forum on Neuropathology Practice was moderated by Dr. Gould and Dr. Keith and focused on safety around autopsy diagnosis of CJD, the Neuropathology workforce analysis in Canada 2019 presented by Dr. Patrick Shannon, and accreditation of neuropathology laboratories in Canada. Digital pathology images from the 14 unknown cases are available for viewing online (www.canp.ca) thanks to the CANP webmaster Dr. Jason Karamchandani.

The Presidential Symposium 2019 on Neurodegenerative Neuropathology featured the Jerry Olszewski Lecture given by Dr. Douglas Munoz on Using eye tracking to identify behavioural biomarkers of neurodegeneration, the David Robertson lecture given by Dr. Tom Beach on Staging systems for Lewy body diseases, and the Gordon Mathieson lecture given by Dr. Ian Mackenzie on C9orf72: FTD, ALS and beyond. The program was completed Dr. Gabor Kovacs’ presentation on Tau pathologies in the aging brain and Dr. Carmela Tartaglia’s presentation on Dementia; the times they are a changing.

The award for best clinical science presentation by a trainee (Dr. Mary Tom Award) in 2019 went to Dr. Suzy Kosteniuk (Supervisor Dr. Lothar Resch), and the award for best basic science presentation by a trainee (Dr. Morrison H. Finlayson Award) was won by Hoang D. Nguyen (Supervisor Dr. Maxime Richer).

The following abstracts were presented at the 59th annual meeting of the Canadian Association of Neuropathologists – Association Candienne des Neuropathologistes (CANP-ACNP) in October 2019.

Patients with Parkinson’s disease (PD) may undergo several elective and emergency surgeries. Motor fluctuations, the presence of a wide range of non-motor symptoms (NMS), and the use of several medications, often not limited to dopaminergic agents, make the perioperative management of PD challenging. However, the literature on perioperative management of PD is sparse. In this descriptive review article, we comprehensively discuss the issues in the pre-, intra-, and postoperative phases which may negatively affect the PD patients and discuss the approach to their prevention and management. The major preoperative challenges include accurate medication reconciliation and administration of the dopaminergic medications during the nil per os (NPO) state. While the former can be addressed with staff education and PD-specific admission protocols, knowledge of non-oral formulations of dopaminergic agents (apomorphine, inhalational levodopa, and rotigotine transdermal patch) is the key to the management of the Parkinsonian symptoms in NPO state. Deep brain stimulation (DBS) devices should be turned off to avert potential electromagnetic interference with surgical appliances. Choosing the appropriate anesthesia and avoiding and managing respiratory issues and dysautonomia are the major intraoperative challenges. Timely reinitiation of dopaminergic medications, adequate management of pain, nausea, and vomiting, and prevention of postoperative infections and delirium are the postoperative challenges. Overall, a multidisciplinary approach is pivotal to prevent and manage the perioperative complications in PD. Administration of anti-Parkinson medications during NPO state, prevention of anesthesia-related complications, and timely rehabilitation remain the key to healthy surgical outcomes.

Hemispherectomy is a unique epilepsy surgery procedure that has undergone significant modification and evolution since Dandy’s early description. This procedure is mainly indicated to treat early childhood and infancy medically intractable epilepsy. Various epileptic syndromes have been treated with this procedure, including hemimegalencephaly (HME), Rasmussen’s encephalitis, Sturge–Weber syndrome (SWS), perinatal stroke, and hemispheric cortical dysplasia. In terms of seizure reduction, hemispherectomy remains one of the most successful epilepsy surgery procedures. The modification of this procedure over many years has resulted in lower mortality and morbidity rates. HME might increase morbidity and lower the success rate. Future studies should identify the predictors of outcomes based on the pathology and the type of hemispherectomy. Here, based on a literature review, we discuss the evolution of hemispherectomy techniques and their outcomes and complications.

The Canadian Association of Neuropathologist – Association canadienne des neuropathologistes (CANP-ACNP) held their 60th annual meeting via Zoom from October 15th to 17th, 2020, under the leadership of Dr. Peter Gould, President of the CANP-ACNP, Dr. Peter Schutz, Secretary Treasurer of the CANP-ACNP, and with technical support from CANP administrators Heather Dow and Colleen Fifield.

The academic program comprised 10 scientific abstracts, 10 unknown cases, a symposium on Neuromuscular Pathology, and a Neuropathology Practice lecture by Dr. Emina Torlakovic entitled The Fall and Rise of Immunohistochemistry. The interactive forum on Neuropathology Practice was moderated by Dr. Gould and Dr. Keith and focused on forensic neuropathology in Canada. The Jerzy Olszewski Lecture was delivered by Dr. Alex Rajput and Dr. Ali Rajput on Neuropathology and Saskatchewan Movement Disorders Program. Digital pathology images from the 10 unknown cases are available for viewing online (www.canp.ca) thanks to the CANP webmaster Dr. Andrew Gao.

The Presidential Symposium 2020 on Neuromuscular Pathology featured the David Robertson Lecture given by Dr. Werner Stenzel entitled The Inflammatory Myopathies – Essential Role of Muscle Biopsies for Precise Diagnosis and the Gordon Mathieson Lecture delivered by Dr. Benjamin Ellezam on The Role of Muscle Biopsy in the Molecular Era: Practical Pointers in Diagnostic Pathology of Inherited Myopathies. The program was completed by Dr. Robert Schmidt’s presentation on Perspectives on the Evaluation of Nerve Biopsies, and Dr. Jodi Warman Chardon’s presentation on MRI & Diagnosis of Muscle Disease.

The Mary Tom Award for best clinical science presentation by a trainee went to Dr. Noor Alsafwani (Supervisor Dr. A. Gao), and the Morrison H. Finlayson Award for best basic science presentation by a trainee was won by Dr. Delaney Cosma (Supervisor Dr. R. Hammond).

The following abstracts were presented at the 60th annual meeting of the Canadian Association of Neuropathologists – Association candienne des neuropathologistes (CANP-ACNP) in October 2020.

Background: Pandemics may promote hospital avoidance among patients with emergencies, and added precautions may exacerbate treatment delays. Methods: We used linked administrative data and data from the Quality Improvement and Clinical Research Alberta Stroke Program – a registry capturing stroke-related data on the entire Albertan population(4.3 million) – to identify all patients hospitalized with stroke in the pre-pandemic(01/01/2016-27/02/2020) and COVID-19 pandemic(28/02/2020-30/08/2020) periods. We examined changes in stroke presentation rates and use of thrombolysis and endovascular therapy(EVT), adjusted for age, sex, comorbidities, and pre-admission care needs; and in workflow, stroke severity(National Institutes of Health Stroke Scale/NIHSS), and in-hospital outcomes. Results: We analyzed 19,531 patients with ischemic stroke pre-pandemic versus 2,255 during the pandemic. Hospitalizations/presentations dropped(weekly adjusted-incidence-rate-ratio[aIRR]:0.48,95%CI:0.46-0.50), as did population-level incidence of thrombolysis(aIRR:0.49,0.44-0.56) or EVT(aIRR:0.59,0.49-0.69). However, proportions of presenting patients receiving thrombolysis/EVT did not decline (thrombolysis:11.7% pre-pandemic vs 13.1% during-pandemic, aOR:1.02,0.75-1.38). For out-of-hospital strokes, onset-to-door times were prolonged(adjusted-coefficient:37.0-minutes, 95%CI:16.5-57.5), and EVT recipients experienced greater door-to-reperfusion delays(adjusted-coefficient:18.7-minutes,1.45-36.0). NIHSS scores and in-hospital mortality did not differ. Conclusions: The first COVID-19 wave was associated with a halving of presentations and acute therapy utilization for ischemic stroke at a population level, and greater pre-/in-hospital treatment delays. Our data can inform public health messaging and stroke care in future pandemic waves.

Background: Amyotrophic lateral sclerosis (ALS) is highly heterogeneous with survival rate ranging from months to decades. Approximately 10-20% of patients develop a rapidly progressive disease and may die within the first year. Therefore, there is an increasing need for an early detection of unique molecular signatures associated with more aggressive forms of disease as it may help identify therapeutic targets. Methods: To identify a unique molecular signature in fast progressing patients, we recruited 45 sporadic ALS (sALS) patients and 35 age-matched healthy controls and measured 62 immune markers in plasma using cytokines array. Results: We found that leptin was significantly downregulated in plasma of sALS patients and more importantly in fast progressing disease. Immune markers CCL16 and sTNF-RII were significantly increased in rapidly progressing disease. We also found that leptin was significantly downregulated in plasma of SOD1G93A mice across disease stage. This was caused by an increased in levels of phospho-AMPK in mice adipocytes and in adipocytes exposed to fast sALS patients’ plasma. Conclusions: We propose that the combination of decreased plasma leptin levels and up-regulation in CCL16/sTNF-RII may be used as a prognostic biomarker to identify fast progressing ALS patients. This unique immune/metabolic profile may cause dysfunction in metabolic homeostasis.

Sudden unexpected death in epilepsy (SUDEP) remains an important cause of epilepsy-related mortality, especially in patients with refractory epilepsy. The exact cause is not known, but postictal cardiac, respiratory, and brainstem dysfunctions are implicated. SUDEP prevention remains a big challenge. Except for low-quality evidence of preventive effect of nocturnal supervision for SUDEP, no other evidence-based preventive modality is available. Other potential preventive strategies for SUDEP include reducing the occurrence of generalized tonic–clonic seizures using seizure detection devices, detecting cardiorespiratory distress through respiratory and heart rate monitoring devices, preventing airway obstruction (safety pillows), and reducing central hypoventilation using selective serotonin reuptake inhibitors and adenosine and opiate antagonists. However, none of the above-mentioned modalities has been proven to prevent SUDEP. The present review intends to provide insight into the available SUDEP prevention modalities.

Cytomegalovirus (CMV) is among the most common of intrauterine infections against which we have no effective preventative or therapeutic options. The developing nervous system is a frequent target of CMV and while most injuries are subclinical, severe insults leading to microcephaly and migration defects are well known. A 20-week gestational age fetus was found to have several abnormalities on prenatal ultrasound, the most prominent of which was a large echogenic focus in one cerebral hemisphere. Congenital CMV infection was identified by amniocentesis and maternal serology. The pregnancy was ended by early induction of labour for a 368g stillborn infant. Postmortem examination revealed massive intracerebral hemorrhage as the correlate for the sonographic finding. The microscopic examination of the brain was also striking for extensive polymicrogyria, a high burden of CMV and abundant angiocentric CMV pathology. Catastrophic intracerebral hemorrhage has not been previously reported in association with congenital CMV infection. The present case expands the range of potential injuries the developing brain is subject to in the setting of CMV infection and raises the possibility of a direct vascular injury.

We examined recurrence after gross total resection (GTR) or subtotal resection (STR) at St. Michael’s Hospital, Toronto, of 181 cases of atypical meningioma (WHO grade II). In the entire group, Kaplan-Meier survival curves showed that combined necrosis and brain invasion was the feature associated with the worst outcome, followed in order by necrosis, histological variants (clear cell, rhabdoid, and chordoid), high mitotic count, and brain invasion. The highly significant difference between necrosis and brain invasion and necrosis was seen only in patients receiving GTR, and lost in those treated with STR. Adjuvant radiotherapy was associated with worse outcome, more so in patients receiving GTR. In the presence of high mitotic count (defined as >4/10HPF) radiation did not affect recurrence, but necrosis and specially combined necrosis and brain invasion magnified the apparent deleterious effect of adjuvant radiotherapy. In the presence of brain invasion, radiotherapy’s small effect did not reach significance. Since patients were not randomized to adjuvant radiotherapy, these results should not be construed as indicating that this treatment is injurious. It can be stated that in the presence of necrosis and particularly necrosis and brain invasion, but not brain invasion alone, or high mitotic count, atypical meningiomas are more resistant to any possible beneficial effect of radiation in delaying recurrence.

Classification of primary CNS tumours is currently achieved by complementing histologic analysis with molecular information, in accordance with the WHO guidelines, and aims at providing accurate prognosis and optimal patient management. cIMPACT-NOW update 3 now recommends grading diffuse IDH-wild type astrocytomas as grade IV glioblastomas if they bear one or more of the following molecular alterations: EGFR amplification, TERT promoter mutation, and whole-chromosome 7 gain combined with chromosome 10 loss. In this reanalysis of the Cancer Genome Atlas (TCGA) glioma expression datasets, we identified 14 IDH-wt infiltrating astrocytic gliomas displaying a “normal-like (NL)” transcriptomic profile associated with a longer survival rate. Some of these tumours would be considered as GBM-equivalents with the current diagnostic algorithm. A k-nearest neighbors model was used to identify 3-gene signatures able to identify NL IDH-WT gliomas. Genes such as C5AR1 (complement receptor) SLC32A1 (vesicular gamma-aminobutyric acid transporter), and SMIM10L2A (long non-coding RNA) were overrepresented in these signatures which were validated further using the Chinese Glioma Genome and Ivy Glioblastoma Atlases. They showed high discriminative power and correlation with survival. This finding could lead to the validation of an immunohistochemical or PCR test which would facilitate classification of IDH-WT astrocytomas with unclear histological grading. Furthermore, associated signaling pathways might represent novel treatment targets for aggressive tumours.