Standard-of-care for glioblastoma (GBM) includes surgery, radiation and temozolomide. Nearly all tumors recur and 5-year survival is less than 3%. Unmethylated promoter status O6-methylguanine-DNA-methyltransferase (MGMT) is a validated biomarker for temozolomide-resistance. Second-line treatment with bevacizumab has not only failed to improve survival, but has also been shown to induce intratumor hypoxia and increased chemoresistance. VAL-083 is a bi-functional DNA-targeting agent that readily crosses the blood-brain barrier. VAL-083 targets N7-guanine, causing DNA double-strand breaks and cancer cell-death in GBM cancer stem cells (CSCs) and non-CSCs, independent of MGMT. To investigate the in vivo anti-tumor effect of VAL-083+bevacizumab, we used an orthotopic GBM T16 PDX model. All mice carried MGMT-unmethylated, temozolomide-resistant recurrent GBM tumors detected by MRI 35 days post-implantation. Tumor progression was measured by MRI on days 49 and 56, and was calculated for the entire study (day 35 vs. 56) and for the last 7 days (day 49 vs. 56). Mice were grouped into control, bevacizumab, VAL-083, and VAL-083+bevacizmab. VAL-083 treatment started 3 days after bevacizumab treatment to ensure induction of hypoxia. Results: Tumors were significantly smaller in VAL-083-treated mice both compared to control (-83%, p<0.001) and compared to bevacizumab-treated (-75%, p<0.001) mice. Additionally, analysis of tumor growth in-time showed significantly reduced tumor progression for VAL-083+bevacizumab compared to VAL-083 alone (p<0.01). Conclusions: These results show strong in vivo anti-tumor efficacy of VAL-083 against MGMT-unmethylated, recurrent GBM. This effect was further augmented in combination with bevacizumab, providing rationale of clinical investigation of VAL-083+bevacizumab in GBM.

Background: Multidisciplinary treatment programs benefit headache patients. No evidence exists as to whether they change resource use. A historical prospective cohort study was performed to compare the frequency of ambulatory care and emergency department visits for the purposes of headache by patients seen at the Calgary Headache Assessment and Management Program (CHAMP) in the three years before, and after, their first appointment. Methods: Administrative data from Alberta Health was used. All patients seen by a physician at CHAMP from 2003-2013 were included. Sample characteristics were described and the Wilcoxan signed rank sum test was used to compare the number of ambulatory care and emergency department visits in the three years before and after each patient’s first physician appointment at CHAMP. Follow-up visits at CHAMP were excluded from analyses. Results: The median number of ambulatory care visits over three years changed from 4 to 2 (p<0.001). The median number of emergency department visits was zero before and after assessment at CHAMP. The mean number of emergency department visits changed from 1.5 to 1.2 (p<0.0001). Conclusions: Enrollment in a multidisciplinary headache program reduces the number of ambulatory care visits and emergency department visits for purposes of headache.

Background: Epilepsy aphasia spectrum of disorders is characterized by developmental and language regression with EEG abnormalities that include electrical status epilepticus of sleep (ESES). Landau-Kleffner syndrome (LKS) and epileptic encephalopathy with continuous spike-wave during sleep (CSWS) are the most severe presentations. GRIN2A mutations have been recognized as causative. Methods: we present two sisters with different epilepsy phenotypes. A variant of unknown clinical significance (VUS) in GRIN2A gene was found in one of the sisters and her similarly affected father. Results: The first sister presented with focal onset seizures at the age of 3 years accompanied by language and cognitive regression and EEG features consistent of ESES, meeting criteria for LKS. Multiple anticonvulsants were tried until she responded well to steroids regaining developmental milestones. Her 5-year-old sister recently presented with focal onset seizures. Her language development is appropriate. Her EEG showed independent multifocal spikes but no ESES during sleep. Her seizures were controlled on monotherapy anticonvulsants. Conclusions: We observed a variable EEG-clinical phenotype and different severity among these family members as expected with GRIN2A-related disorders. This report contributes to evidence of the GRIN2A variant pathogenicity.

Brain tumor behavior is driven by aberrations in the genome and epigenome. Many of these changes, such as IDH mutations in diffuse low-grade glioma (DLGG), are common amongst the same class of tumour and can be incorporated into the diagnostic criteria. However, any given tumor may have other, less common genomic aberrations that are essential for its biological behavior and may inform on underlying aberrant cellular pathways, and potential therapeutic agents. Precision oncology is a genomics-based approach which profiles these alterations to better manage cancer patients and has established itself within the practice of oncology and is slowly making its way into neuro-oncology. The BC Cancer’s Personalized OncoGenomics (POG) program has profiled 16 adult tumours originating from the central nervous system using whole genome and transcriptome analysis (WGTA), for the first time, within a meaningful clinical timeframe/setting. As expected, primary genomic drivers were consistent with their respective diagnoses, though secondary drivers were found to be unique to each tumour. Although these analyses did not result in altered clinical management for these patients, primarily due to availability of drug or clinical trials, they highlight the heterogeneity of secondary drivers in cancers and provide clinicians with meaningful biological information. Lastly, the data generated by POG has highlighted the frequency and complexity of novel driver fusions which are predicted to behave similarly to canonical driver events in their respective tumours. The information available to clinicians through POG has provided paramount knowledge into the biology of each unique tumour.

Background: CNS innate immune cells, microglia and macrophages (MMs), are the largest component of the inflammatory infiltrate in glioblastoma (GBM). They initially participate in tumor surveillance, but are subverted by GBM. Immunotherapies have proven incredibly successful in cancers such as melanoma, but not against GBM in part because GBM-associated MMs are not well understood. We hypothesized the content and inflammatory phenotype of MMs in GBM is variable between patients. We suspect MMs in IDH-wildtype and –mutant GBMs display divergent inflammatory phenotypes that helps explain the latter's better prognosis. Understanding GBM-associated MM heterogeneity will allow for better immunotherapy development and selection. Methods: MMs were isolated from untreated human IDH-wildtype and -mutant GBMs using flow cytometry and cultured for collection of conditioned media and analysis of secretory products. Automated segmentation with a high-content analysis system was used to quantitate MM content and inflammatory phenotype in frozen sections. New bioinformatics techniques allowed the comparison of MM profiles in publicly available single-cell RNA-sequencing databases with IDH-wildtype and -mutant GBMs. Results: Surprisingly marked variation in MM content exists between GBMs ranging from ~0-70%. A mixture of pro- and anti-inflammatory MMs are found in each GBM. Interestingly, IDH-mutant GBM-associated MMs were more activated than MMs in IDH-wildtype GBMs. Conclusions: Taken together, the highly variable MM content and phenotype of GBMs suggests the success of immunotherapies hinges on taking a precision medicine approach. MM-rich GBMs would benefit more from therapies that target them. MM activation in IDH-mutant GBMs may contribute to better patient prognoses.

Background: Childhood primary angiitis of the central nervous system (cPACNS) is a rare inflammatory disease of brain vessels. The small vessel subtype is diagnosed on brain biopsy and often presents with cognitive and behavioural changes, headaches and seizures. However, there are few reported cases of super-refractory status epilepticus. Methods: We present a case of small vessel cPACNS complicated by super-refractory status epilepticus and review the literature. Results: Our patient is a previously healthy 11-year-old boy who presented with new-onset seizures and encephalopathy in the context of fever. He developed super-refractory status epilepticus, requiring burst suppression for four weeks with various IV infusions. During this time, he was on the ketogenic diet and tried eight anti-seizure medications. Extensive investigations included brain biopsy confirming small vessel cPACNS. He was treated with IV methylprednisolone, oral steroids, IVIG, and cyclophosphamide. After prolonged rehabilitation, he recovered almost completely and has a normal neurological examination with no epileptiform activity on EEG. Conclusions: Small vessel cPACNS should be considered in the differential diagnosis of super-refractory status epilepticus. Despite being in SE for four weeks, symptomatic management of seizures and immunosuppression to treat the underlying pathology resulted in favourable neurological outcomes. This is one of the longest cases of SE in small vessel cPACNS in the literature.

Background: Hemifacial Spasm (HFS) is rarely caused by a dolichoectatic vertebrobasilar artery (eVB) compression of the Facial Nerve. This can pose a surgical challenge when performing microvascular decompression as vessel mobilization is often difficult due to atherosclerosis, tethering from brainstem perforators, and large size. These patients are often not considered for surgery. Methods: A retrospective chart review of patients who were surgically treated by the senior author between 2003 and 2017 with an admitting diagnosis of HFS was performed. Patients with preoperative neuroimaging demonstrating eVB compression of their facial nerve/root were included. Results: During the 15-year review, 315 patients underwent microvascular decompression for HFS and 21 (6.7%) had dolichoectactic vertebrobasilar compressions. At final followup (>3 months) 19 patients (90.4%) experienced reduction in symptoms with 15 (71.4%) having complete resolution. One patient required re-operation and benefitted from subsequent symptom relief. The majority of culprit compression was found proximally on the pontine surface. Mobilization of the culprit vessel was achieved successfully in the majority of cases with Teflon pledgets. There were no perioperative strokes or death. Complications are presented Conclusions: Microvascular Decompression for Hemifacial Spasm caused by dolichoectatic vertebrobasilar artery compression can be performed with a high rate of safety and success in the setting of a high case volume centre.

Group-3 medulloblastoma (MBL) is highly resistant to radiation (IR) and chemotherapy and has the worst prognosis. Hence, there is an urgent need to elucidate targets that sensitize these tumors to chemotherapy and IR. Employing standard assays for viability and sensitization to IR, we identified PRDX1 as a therapeutic target in Group-3 MBL. Specifically, targeting PRDX1 by RNAi or inhibition by Adenanthin led to specific killing and sensitization to IR of Group-3 MBL cells. We rescued sensitization of Daoy and UW228 cells by hypermorphic expression of PRDX1. PRDX1 knockdown caused oxidative DNA damage and induced apoptosis. We correlated PRDX1 expression to patient outcomes in a validated MBL tumor-microarray. Whole genome sequencing identified pathways/genes that were dysregulated with PRDX1 inhibition or silencing. Our in vivo studies in mice employing flank/orthotopic tumors from patient derived xenografts/Group-3 MBL cells confirmed in vitro observations. Animals with tumors in which PRDX1 was targeted by RNAi or Adenanthin (using mini osmotic pumps) showed decreased tumor burden and increased survival when compared to controls. Since, Adenanthin does not cross the blood brain barrier (BBB) we used HAV6 peptide to transiently disrupt the BBB and deliver Adenanthin to the tumor. Immunohistochemistry confirmed that targeting PRDX1 resulted in increased oxidative DNA damage, apoptosis and decreased proliferation. In summary, we have validated PRDX1 as a therapeutic target in group-3 MBL, identified Adenanthin as a potent chemical inhibitor of PRDX1 and confirmed the role of HAV peptide (in the transient modulation of BBB permeability) in an orthotopic model of group-3 MBL.

Background: MS related trigeminal neuralgia (MS-TN) is associated with high recurrence and retreatment rates. Optimal treatment and role for partial sensory rhizotomy (PSR) for MS-TN remains to be determined. Methods: We analyzed time to treatment failure (TTF) after PSR (n=14) versus other prior procedures (n=53) among 12 consecutively treated MS-TN patients. Kaplan-Meier curves and Log-Rank tests were utilized to compare BNI pain scores and TTF after PSR vs prior procedures using the same patient cohort as their own control group. Subsequent analysis compared TTF after PSR to other procedures (n=93) among a second cohort of 18 MS-TN patients not undergoing PSR. Results: TTF was significantly longer after PSR compared to prior procedures among the PSR cohort (p<0.0001) with median TTF of 79 vs 10 months respectively. Similarly, there was a longer TTF after PSR compared to prior procedures among the MS-TN cohort with median TTF 79 vs 16 months respectively (p<0.001). PSR resulted in a higher proportion of excellent pain scores when compared to prior procedures in the MS-TN cohort (77% vs 29%, p<0.001). Conclusions: TTF was significantly longer following partial sensory rhizotomy compared to other prior procedures in MS-TN patients. A higher proportion of patients achieved excellent BNI pain scores after PSR.

Introduction: Diffuse intrinsic pontine glioma (DIPG) is refractory to therapy. The identification of histone H3.1/H3.3 K27M mutations in most DIPG has provided new insights. The DLX homeobox genes are expressed in the developing forebrain. The Dlx1/Dlx2 double knockout (DKO) mouse loses tangential GABAergic interneuron migration to the neocortex. We have identified genes that encode glutamic acid decarboxylase (GAD) enzymes as direct targets of DLX1/DLX2. In DIPG patients with H3.3 K27M mutations there is decreased Dlx2 and increased expression of the myelin transcription factor, Myt1. Methods and Results: We used bioinformatics approaches and chromatin immunoprecipitation (ChIP) assays to identify Olig2, Nkx2.2 and Myt1 promoter sequences as candidate DLX2 targets in vivo. DNA binding specificity was confirmed. The functional consequences of Dlx2 co-expression with reporter constructs of ChIP-isolated promoter fragments of Olig2 and Nkx2.2 demonstrated repression of gene targets in vitro. qPCR showed increased Olig2 and Nkx2.2 expression in the DKO forebrain. Stable transfection of a murine DIPG cell line with Dlx2 resulted in increased Gad1 and Gad2 and decreased Olig2 and Nkx2.2 expression. Of significance, we demonstrated decreased expression of H3.3 K27M and restoration of H3.3 K27 tri-methylation (me3). Conclusions: DLX transcription factors promote GABAergic interneuron and concomitant inhibition of oligodendroglial differentiation in neural progenitors by repression of a suite of genes including Olig2 and Nkx2.2. Restoration of H3 K27me3 expression in DIPG provides a promising lead towards exploration of differentiation as a therapeutic strategy for DIPG.

Background: Migraines are sub-optimally treated, affect millions of Canadians, and are underrepresented in medical training. A study was conducted to identify the needs of Canadian Healthcare Providers (HCPs) for migraine education, with the aim to inform the development of learning activities. Methods: This ethics-approved study was deployed in two consecutive phases using a mixed-methods approach. Phase 1 (qualitative) explored the causes of challenges to migraine care via a literature review, input from an expert working group, and semi-structured interviews with multiple stakeholders. Phase 2 (quantitative) validated these causes using an online survey. Results: The study included 103 participants (28 in phase 1; 75 in phase 2): general practitioners=37; neurologists=24; nurses=14; pharmacists=20; administrators, policy influencers and payers=8. Four areas of sub-optimal knowledge were identified: (1) Canadian guidelines, (2) diagnostic criteria, (3) preventive treatment, and (4) non-pharmacological therapies. Attitudinal issues related to the management of migraine patients were also identified. Detailed data including the frequencies of knowledge gaps among general practitioners and general neurologists will be presented along with qualitative findings. Conclusions: Educational activities for general practitioners and general neurologists who treat patients with migraines should be designed to address the four educational needs described in this study.

The Canadian Brain Tumour Registry (CBTR) project was established in 2016 with the aim of enhancing infrastructure for surveillance and clinical research to improve health outcomes for brain tumour patients in Canada. We present a national surveillance report on malignant primary brain and central nervous system (CNS) tumours diagnosed in the Canadian population from 2009-2013. Patients were identified through the Canadian Cancer Registry (CCR); an administrative dataset that includes cancer incidence data from all provinces/territories in Canada. Cancer diagnoses are coded using the ICD-O3 system. Tumour types were classified by site and histology using The Central Brain Tumour Registry of the United States definitions. Incidence rates (IR) and 95% confidence intervals (CI) were calculated per 100,000 person-years and standardized to the 2011 census population age-distribution. Overall, 12,115 malignant brain and CNS tumours were diagnosed in the Canadian population from 2009-2013 (IR:8.43;95%CI:8.28,8.58). Of these, 6,845 were diagnosed in males (IR:9.72;95%CI:9.49,9.95) and 5,270 in females (IR:7.20;95%CI:7.00,7.39). The most common histology overall was glioblastoma (IR:4.06;95%CI:3.95,4.16). Among those aged 0-19 years, 1,130 malignant brain and CNS tumours were diagnosed from 2009-2013 (IR:3.36;95%CI:3.16,3.56). Of these, 625 were diagnosed in males (IR:3.32;95%CI:3.34,3.92) and 505 in females (IR:3.08;95%CI:2.81,3.36). The most common histology among the paediatric population was pilocytic astrocytoma (IR:0.73;95%CI:0.64,0.83). The presentation will include: IRs for other histologies, the geographic distribution of cases and a comparison between Canada and the United States.

Introduction: Radiation-induced meningiomas (RIMs) are increasing in prevalence as cancer patients live longer. Our laboratory has demonstrated that RIMs have a unique genomic landscape compared to sporadic meningiomas. Notably, a subset of RIMs harbor genomic rearrangement resulting in NF2 gene fusion with a nonrecurrent reciprocal gene. We aimed to compare the gene expression of NF2-Fusion and NF2-Wild Type (NF2-WT) RIMs. Methods: RNA sequencing using Illumina HiSeq was performed on 7 NF2-Fusion and 12 NF2-WT RIMs. Short read sequences obtained from sequencing were mapped to reference human genome(hg19). We performed differential expression analysis using edgeR statistical packages. Pathway analysis was performed using Gene Set Enrichment Analysis (GSEA). Immunohistochemistry was performed to validate findings. Results: Principal component analysis revealed that 5/7 of NF2-Fusion RIMs had similar gene expression profiles. One outlier had no chromosome 1p loss like the other NF2-Fusion RIMs. Pathway analysis demonstrated there was an upregulation of immune pathways in NF2-Fusion RIMs. Immunohistochemistry of PD-L1 revealed that 0/7 and 7/7 of NF2-Fusion tumors had positive expression in tumoral and inflammatory cells, respectively. In comparison, 6/12 of RIMs had tumoral and inflammatory cell expression of PD-L1. In addition, there was a higher CD3 lymphocyte infiltration in NF2-WT (42.2 vs. 12.4 number of cells per HPF). Discussion: Preliminary data in our lab demonstrates that NF2-Fusion tumors have a distinct immune microenvironment compared to NF2-WT tumors. Although pathway analysis indicates that NF2-Fusion RIMs have overexpression of immune pathways, immunohistochemistry reveals that inflammatory cells have positive PD-L1 expression, suggestive of immune burnout.

Background: Headache is one of the most frequent complaints in primary care. We reviewed headache questions submitted to an electronic consultation service in Ontario to classify the types of headaches and describe the questions being asked. We also identified reasons why answers were not retrievable within UpToDate, an online clinical resource. Methods: 65 headache eConsults were further divided into 85 questions and categorized by headache type and question theme. Questions were manually searched within UpToDate to determine if they could be answered using this resource. The intent to refer the patient for a face-to-face referral after the eConsult was collected. Results: The top classifications were migraine, unclassified headache, and exertional and/or coital headache. The themes -identified were medication questions (41.7%), investigation questions (33.3%), clinical concerns despite normal neurologic exam and/or imaging (15.5%); and abnormal imaging findings (9.5%). Answers to 40.1% of the questions were not retrievable in UpToDate. The main reason for irretrievability was an unusual presentation. Only 33.8% of eConsults resulted in a face-to-face referral to a specialist. Conclusions: Although electronic resources may be useful in some cases, clinical nuances cannot be accounted for. By providing physicians with rapid access to specialists, eConsult services may obviate the need for formal, face-to-face referrals.

Background: Granulomatosis with polyangitis (GPA) is a rare systemic vasculitis with a prevalence of 0.6 per million in the pediatric population. CNS involvement occurs in 7-18% of cases. Pituitary involvement is only noted in 1% of cases. Methods: A 16-year-old girl with newly-diagnosed GPA presented to our hospital with progressive debilitating headaches, polyuria, and polydipsia. Results: Initial MRI showed changes to the pituitary. Lumbar puncture (LP) revealed opening pressure of 26. She developed central diabetes insipidus (DI) and visual changes. Repeat head imaging showed adenohypophysitis. The GPA was previously treated with steroids and cyclophosphamide, followed by Cellcept. Once the pituitary involvement was discovered, she was given re-induction therapy with Rituximab and steroid dose was increased. DI is being treated with DDAVP. Her headaches are improving. Conclusions: CNS inflammatory diseases are rare in childhood. Pituitary involvement is extremely rare in GPA. Induction therapy for adults with GPA and pituitary involvement includes glucocorticoids and cyclophosphamide, which often leads to improvement of MRI abnormalities but is not effective in resolving pituitary dysfunction. Our patient had already received this treatment when she developed the CNS findings. This case demonstrates that cerebral involvement is often resistant to classic therapy, and one should be vigilant in looking for CNS inflammation in these patients.

Background: In RRMS patients with inadequate response to prior therapy, 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved outcomes versus SC IFNB-1a over 2 years (CARE-MS II [NCT00548405]). Efficacy remained durable in a 4-year extension (NCT00930553); patients could receive as-needed alemtuzumab retreatment (≥12 months apart) for disease activity, or another disease-modifying therapy (DMT). Through Year 6, 88% remained on study; 50% received neither alemtuzumab retreatment nor another DMT; 16% received ≥4 courses; 3% received ≥5 courses. We evaluated Course 4 (C4) efficacy in patients receiving ≥4 courses. Methods: Annualized relapse rate (ARR); improved/stable Expanded Disability Status Scale (EDSS) score (versus baseline); 6-month confirmed disability improvement (CDI). 11% of patients met inclusion criteria: ≥4 courses within 60 months of baseline; no DMT. Those receiving C5 were censored at that time. Results: ARR decreased after C4 (12 months pre-C4 [-12M]: 0.75; 12 months post-C4 [+12M]: 0.19; P<0.0001), remaining low (0.23) at Year 3 post-C4. More patients had stable/improved EDSS scores +12M (67.5%) versus at C4 administration (53.5%). Percentage with CDI increased post-C4 (-12M: 10.0%; +12M: 26.7%). Conclusions: C4 reduced relapses and stabilized/improved disability in patients with disease activity after initial treatment (C1, C2) plus one additional course (C3).

Background: The 2005, 2010, and 2017 McDonald diagnostic criteria for multiple sclerosis (MS) were compared at baseline in participants of a Canadian multicentre clinical trial of minocycline in clinically isolated syndrome (CIS). Methods: The cohort included 142 participants. Baseline clinical and imaging data were used to determine if participants met criteria for dissemination in space (DIS) and time (DIT) as required for each version of the criteria. We also explored the impact of permitting a clinical diagnosis of transverse myelitis to represent a spinal cord lesion, and for multifocal clinical onset to represent DIS. Results: The clinical trial excluded patients meeting the 2005 McDonald criteria at baseline. The 2010 criteria were met by 28.9% (41/142) of participants. If a multifocal clinical presentation was considered evidence of DIS 29.6% (42/142) met the 2010 criteria. The 2017 criteria were met by 36.7% (52/142). Allowing a clinical diagnosis of transverse myelitis to confirm a spinal lesion, or multifocal onset to confirm evidence of DIS, led to a diagnosis in 38% (54/142) and 38.7% (55/142), respectively. Conclusions: This study confirms that each revision of the McDonald diagnostic criteria allowed an MS diagnosis in more CIS patients at onset. Exploration of other modifications suggests further improvement may be possible.

Background: Opportunistic infection should be considered when seeing neurological complications in the setting of immunosuppression. Accumulating evidence that enteroviral meningoencephalitis can occur after rituximab administration exists but differentiating it from non-infectious conditions can be challenging. Methods: Case report Results: We describe a 4 year-old-boy with a history of pulmonary capillaritis, treated with immunosuppressive therapy -including steroids, rituximab, and azathioprine. He developed mutism and ataxia after 18 months on rituximab. MRI Brain/Spine revealed extensive T2/FLAIR hyperintensities in the deep subcortical white matter, temporal lobes, globus pallidi, thalami, brainstem, and cerebellum; and swelling of the dorsal cervical cord, showing primarily grey matter involvement. IgG levels had a decreasing trend over the course of Rituximab. CSF, and subsequent brain biopsy, were both positive for enterovirus RNA by RT-PCR. He was thought to have enterovirus encephalitis secondary to rituximab therapy, and was treated with IVIG and fluoxetine. Conclusions: One should consider chronic opportunistic CNS infections in children treated with immunosuppressive therapy, and to consider chronic enterovirus infection when B-cell suppression has occurred. As rituximab is being increasingly used in the pediatric population, and is generally thought to be safe, attention should be paid to any child with chronic neurological signs, particularly younger children who may be at higher risk for chronic enterovirus infection.

Background: Anti-NMDAR Encephalitis is an autoimmune disease of children and adults which most often presents with sub-acute psychiatric disturbance or seizures, but includes a broad group of potential clinical manifestations. Routine neuroimaging, such as cerebral MRI, is often nonspecific or normal. Methods: This study reports a series of retrospectively reviewed pediatric patients with AntiNMDAR encephalitis with emphasis on the evolution of clinical features over time, cerebral MRI, 18-FDG Positron emission tomography (PET) findings, and post illness neurocognitive features. Results: Four cases of Antibody confirmed AntiNMDAR encephalitis were included, two male and two female, of a mean of 13 years of age. Patients had a mean of three symptom categories by presentation, though many of these were subtle, progressing to 6.5 by the end of the first month. MRI, CSF and EEG were abnormal for one, three and all patients, respectively. All patients had abnormal cerebral PET scans, and all displayed some temporal lobe hypermetabolism on either initial or repeat cerebral PET Scan. Conclusions: Anti-NMDAR encephalitis is a variable disorder with an evolving clinical presentation in children. Temporal hypermetabolism on cerebral PET may be a time dependent feature of the disorder.