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.

Background: The mechanism of aneurysmal healing after flow-diversion treatment of cerebral aneurysms remains unknown. The purpose of this research to is to utilize a novel technology called endovascular optical coherence tomography (OCT) to characterise and improve our understanding of aneurysmal healing after flow-diversion using a rabbit aneurysm model. Methods: Saccular aneurysms were created in 10 New Zealand white rabbits. The aneurysms were treated with a flow-diverting stent 28 days after creation. OCT and histopathologic examinations included: luminal thrombosis, endothelial loss, inflammation, fibrin, smooth muscle cell loss, disruption of the internal and external elastic lamina, and tunica adventitia changes Results: OCT revealed endothelialization across the stent, appearing to originate from the parent vessel, along with small amounts of thrombus on the stent-struts. Minimal thrombus was visualized within the aneurysm sac. Histologic examination revealed that OCT can accurately define endothelialization across the sent, and define patent segments across the neck. Conclusions: Aneurysmal healing appears to originate at the parent vessel/stent interface, and use the stent as a scaffold to grow across the neck of the aneurysm. Minimal thrombus was visualized within the aneurysm sac, with ongoing flow observed in the setting of incomplete neck endothelialization. This technology has great potential for assessing aneurysmal healing in real-time.

Toxoplasmosis is an opportunistic infection caused by Toxoplasma gondii (TG), commonly involving the brain. Symptomatic clinical disease of TG infection is much more commonly associated with immunodeficiency; clinicopathological manifestations of brain toxoplasmosis are linked to individual immune responses including brain infiltration of T-cells that are thought to fight against toxoplasmosis. In patients with autoimmune diseases, immune status is typically characterized by T-cell infiltration and complicated mainly by immunosuppressant and/or immunomodulatory treatment. In this study, we demonstrate clinical and radiological features correlated with pathological features of brain toxoplasmosis at different disease stages in a patient with coexisting autoimmune diseases, including systemic lupus erythematosus and autoimmune hepatitis. The infiltration of CD8+ T-cells in toxoplasma immunostaining-positive acute lesions was greater than that in toxoplasma immunostaining-negative chronic lesions. We also review previously reported cases of brain toxoplasmosis with comorbid autoimmune diseases. Our present case and literature review suggest that brain toxoplasmosis in patients with autoimmune diseases may be asymptomatic unless disease complications occur; it may present as an incidental finding at postmortem examination of rapidly developed lesions. T-cell infiltration in patients with autoimmune diseases and coexisting toxoplasmosis may be at least partially reduced; ultimately, the roles of T-cell infiltration in brain toxoplasmosis deserve further investigation.

We report the neuropathology of two pediatric brain biopsy cases associated with serum anti-myelin oligodendrocyte glycoprotein (MOG) positivity. Descriptions of anti-MOG associated neuropathology are limited, with initial reports describing various patterns of inflammatory demyelination. Our first patient presented with confusion, speech abnormalities and personality changes following a treated strep throat infection. Our second patient had a past medical history of neurofibromatosis type 1 (NF1) and presented with hypersomnolence and focal neurological deficits. MRI abnormalities included diffuse scattered T2 FLAIR hyperintensities +/- enhancement. CSF was positive for anti-MOG antibodies in both cases, while one case exhibited additional anti-NMDA-R antibodies. Brain biopsies revealed vasocentric mononuclear inflammation featuring a predominance of lymphocytes that included intramural forms, as well as diffuse microglial activation, but no evidence of microglial nodules or microorganisms. One case demonstrated mild perivascular demyelination. The prevailing pattern in both cases was suggestive of “small vessel childhood primary angiitis of the central nervous system” (SVcPACNS). Our results parallel recent reports of anti-MOG neuropathology describing small vessel vasculitis, contrary to initial and subsequent reports that describe “encephalitis”. The foregoing suggests that the neuropathology associated with serum anti-MOG positivity may be broader than first appreciated. Moreover, this pattern of vasculitis might have implications for the natural history of this nascent disorder.

Background: Quantitative susceptibility mapping (QSM) is an MR sequence that has potential as a biomarker in concussion. We compared QSM in pediatric concussion patients versus a comparison group of children with orthopedic injuries (OI) and assessed QSM’s performance relative to the current clinical benchmark (5P risk score) for predicting persistent postconcussion symptoms (PPCS). Methods: Children (N=967) aged 8-16.99 years with either concussion or OI were prospectively recruited from 5 Canadian centers. Participants completed QSM at a post-acute assessment 2-33 days post-injury. QSM z-score metrics for 9 regions of interest (ROI) were derived from 371 children (concussion=255, OI=116). PPCS at 1-month post-injury was defined using reliable change methods. Results: The concussion and OI groups did not differ significantly in QSM across ROI. Increased frontal white matter (WM) susceptibility predicted reliable increases in parent-rated cognitive symptoms (p=0.001). Together, frontal WM susceptibility and the 5P risk score were better at predicting persistent cognitive symptoms than the 5P risk score alone (p=0.0021). AUC were 0.71(95%CI: 0.62-0.80) for frontal WM susceptibility, 0.67(95%CI: 0.56-0.78) for the 5P risk score, and 0.73(95%CI: 0.64-0.82) for both. Conclusions: This is the first study to demonstrate a potential imaging biomarker that predicts persistent symptoms in children with concussion compared to the current clinical benchmark.

Perinatal stroke occurs around the time of birth and leads to lifelong neurological disabilities including hemiparetic cerebral palsy. Magnetic resonance imaging (MRI) has revolutionized our understanding of developmental neuroplasticity following early injury, quantifying volumetric, structural, functional, and metabolic compensatory changes after perinatal stroke. Such techniques can also be used to investigate how the brain responds to treatment (interventional neuroplasticity). Here, we review the current state of knowledge of how established and emerging neuroimaging modalities are informing neuroplasticity models in children with perinatal stroke. Specifically, we review structural imaging characterizing lesion characteristics and volumetrics, diffusion tensor imaging investigating white matter tracts and networks, task-based functional MRI for localizing function, resting state functional imaging for characterizing functional connectomes, and spectroscopy examining neurometabolic changes. Key challenges and exciting avenues for future investigations are also considered.

Flow cytometry of the cerebrospinal fluid (CSF) is used in isolation or as an adjunct to cytology to increase the sensitivity of detecting primary central nervous system (CNS) lymphoma. We aim to evaluate the sensitivity of CSF flow cytometry as a diagnostic tool for primary CNS lymphoma in patients presenting with undifferentiated neurologic symptoms. We retrospectively reviewed all CSF samples received by the Calgary Laboratory Services Flow Cytometry Laboratory from 2012- 2015. Clinical data, laboratory investigations, radiologic imaging studies, and pathological data were analyzed. Clinical review extended to 2 years post CSF flow cytometric testing. The number of samples of CSF flow cytometry that were positive for a hematological malignancy was 43/763 (5.6%). The overall sensitivity of the test was 69.4%. A positive result was more likely to occur in patients with a prior history of a hematological malignancy or abnormal enhancement on MRI (p<0.0001). CSF flow cytometry was negative in all patients who did not have a previous hematological malignancy or abnormal enhancement on MRI (n = 247). CSF flow cytometry has a limited role in screening for primary CNS lymphoma, unless a strictly endorsed testing algorithm is applied. It is, however, an invaluable tool in evaluating CNS involvement in patients with a previous diagnosis of hematolymphoid malignancy or abnormal enhancement on MRI.

Background: Sample entropy (SampEn) can quantify the unpredictability of a physiological signal. We sought to assess if SampEn on EEG could reflect recent seizure activity. Methods: Charts of all patients undergoing an outpatient EEG between January and March 2018 were reviewed to assess seizure occurrences in the follow-up period between the two clinical visits surrounding the EEG. 9s-EEG segments were extracted at pre-specified time points. SampEn was calculated for all segments and values aggregated at the 25thpercentile. We performed a multivariate zero-inflated analysis to test the association between SampEn and seizure rate around the EEG, after controlling for age, presence of IED, presence of abnormal slowing, and presence of a focal brain lesion. Results: 269 EEGs were screened and 133 met inclusion criteria (112 patients). 80 EEGs (60%) were from patients with epilepsy, of which 47 had at least one seizure within the year preceding the EEG. Remaining EEGs were from patients who were deemed not to have epilepsy at last follow-up. Each 1SD decrease in SampEn was associated with a 3.93-fold increase in the rate of daily seizures (95% CI: 1.19–12.99, p = 0.02). Conclusions: Sample entropy of EEG is a potential objective method to assess contemporary seizure occurrence.

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumefactive lesion with unclear pathogenesis. It is diagnosed by pathological findings of the typical histological features that include granular amorphous cores with palisading spindle to epithelioid cells, variable fibrous stroma, foreign-body reaction with giant cells, and calcification/ossification occasionally with psammoma bodies. However, its histopathology may be variable and currently immunohistochemistry plays a limited role in its diagnosis and understanding the pathogenesis. In this study, we examined 6 cases of CAPNONs including 3 intracranial and 3 spinal epidural lesions (age range: 59–69 years; 3 males and 3 females). Immunohistochemistry revealed that all CAPNON cores contain abundant positive deposits of neurofilament protein (NFP), which was supported by electron microscopy finding of filaments (8–13 nm in diameter). In comparison, no NFP positivity was found in 5 psammomatous/metaplastic meningiomas or 7 intervertebral tissue lesions with calcification/ossification. In addition, CAPNON cellular areas showed variable numbers of CD8+ cytotoxic T-cells with less CD4+ T-cells and a decreased ratio of CD4/CD8+ cells, versus the intervertebral tissue lesions without CD8+ or CD4+ cells. Our findings suggest that NFP may be a principal constituent of CAPNONs, and thus involved in the pathogenesis of CAPNON. Given the decreased CD4/CD8 ratio, the pathogenic process of CAPNON is possibly immune- mediated.

Interventional neuroradiology (INR) has evolved from a hybrid mixture of daring radiologists and iconoclastic neurosurgeons into a multidisciplinary specialty, which has become indispensable for cerebrovascular and neurological centers worldwide. This manuscript traces the origins of INR and describes its evolution to the present day. The focus will be on cerebrovascular disorders including aneurysms, stroke, brain arteriovenous malformations, dural arteriovenous fistulae, and atherosclerotic disease, both intra- and extracranial. Also discussed are cerebral vasospasm, venolymphatic malformations of the head and neck, tumor embolization, idiopathic intracranial hypertension, inferior petrosal venous sinus sampling for Cushing’s disease, and spinal interventions. Pediatric INR has not been included and deserves a separate, dedicated review.