Background: Studies of autopsy-confirmed cases suggest that Parkinson’s disease (PD) prognosis can be predicted using motor symptom severity at first visit. We evaluated the association between motor symptom subtype at first visit and severity at eight years disease duration among clinically-diagnosed cases at the Saskatchewan Movement Disorder Program. Methods: Retrospective data review identified 374 patients with first visit within three years of symptom onset, a clinical diagnosis of idiopathic PD, and a follow-up visit eight years after symptom onset. Subtypes were grouped as tremor-dominant (TD) if tremor was greater than rigidity and bradykinesia, akinetic-rigid (AR) if rigidity or bradykinesia was greater than tremor, and mixed (MX) if patient was neither TD nor AR based on assessment of all four limbs. Primary outcome was disease severity as measured by Hoehn & Yahr score at eight years after symptom onset. Results: The most common subtype was AR (n=164) followed by MX (n=156). TD was least common (n=54). There was no significant difference between subtypes in H&Y scores at eight years disease duration. Conclusions: These findings suggest that early PD prognosis cannot be predicted based on motor symptoms in all four limbs at first visit. Earlier studies had longer follow-up and future studies will examine progression at longer periods of disease duration.

Background: Patients suffering from traumatic brain injury (TBI) are at increased risk of venous thromboembolism (VTE). However, initiation of pharmacological venous thromboprophylaxis (VTEp) may cause further intracranial hemorrhage. We reviewed the literature to determine the postinjury time interval at which VTEp can be administered without risk of TBI evolution and hematoma expansion. Methods: MEDLINE and EMBASE databases were searched. Inclusion criteria were studies investigating timing and safety of VTEp in TBI patients not previously on oral anticoagulation. Two investigators extracted data and graded the papers’ levels of evidence. Randomized controlled trials were assessed for bias according to the Cochrane Collaboration Tool and Cohort studies were evaluated for bias using the Newcastle-Ottawa Scale. We performed univariate meta-regression analysis in an attempt to identify a relationship between VTEp timing and hemorrhagic progression and assess study heterogeneity using an I2 statistic. Results: Twenty-one studies were included in the systematic review. Eighteen total studies demonstrated that VTEp postinjury in patients with stable head computed tomography scan does not lead to TBI progression. Fourteen studies demonstrated that VTEp administration 24 to 72 hours postinjury is safe in patients with stable injury. Four studies suggested that administering VTEp within 24 hours of injury in patients with stable TBI does not lead to progressive intracranial hemorrhage. Overall, meta-regression analysis demonstrated that there was no relationship between rate of hemorrhagic progression and VTEp timing. Conclusions: Literature suggests that administering VTEp 24 to 48 hours postinjury may be safe for patients with low-hemorrhagic-risk TBIs and stable injury on repeat imaging.

Neuroaxonal Dystrophies (NAD) are neurodegenerative diseases characterized by axonal “spheroids” occurring in different age groups. The identification of mutations delineated new molecular entities in these disorders. We report neuropathological data of a new form of NAD, characterized by a precocious prenatal onset, different from classical and connatal Infantile Neuroaxonal Dystrophy (INAD).

We studied 5 fetuses examined after pregnancy termination and 2 term neonates deceased just after birth, 4/7 from consanguineous parents. All subjects presented severe fetal akinesia sequence with microcephaly. In 4/7 cases, a molecular study was performed. In all cases, “spheroids” with typical immunohistochemical features were identified, with variable spreading in the central and peripheral nervous system. Basal ganglia, brainstem, cerebellum and spinal cord involvement was constant. Associated CNS malformations, unusual in INAD, were associated including hydrocephalus (2), callosal agenesis/hypoplasia (2), olfactory agenesis (1), cortical (3) and retinal (1) anomalies. None cases demonstrated mutations in PLA2G6, found in INAD.

The clinical and neuropathological features of these fetal cases are different from those of “classical” INAD. The absence of mutations of PLA2G6, in addition, suggests that the fetal NAD is a new entity, distinct from INAD, with different molecular basis. Associated malformations suggest a wide phenotypic spectrum and probable genetic heterogeneity. Finally, fetal NAD is an additional etiology of fetal akinesia.

Objective: To validate a case definition of multiple sclerosis (MS) using health administrative data and to provide the first province-wide estimates of MS incidence and prevalence for Saskatchewan, Canada. Methods: We used population-based health administrative data between January 1, 1996 and December 31, 2015 to identify individuals with MS using two potential case definitions: (1) ≥3 hospital, physician, or prescription claims (Marrie definition); (2) ≥1 hospitalization or ≥5 physician claims within 2 years (Canadian Chronic Disease Surveillance System [CCDSS] definition). We validated the case definitions using diagnoses from medical records (n=400) as the gold standard. Results: The Marrie definition had a sensitivity of 99.5% (95% confidence interval [CI] 92.3-99.2), specificity of 98.5% (95% CI 97.3-100.0), positive predictive value (PPV) of 99.5% (95% CI 97.2-100.0), and negative predictive value (NPV) of 97.5% (95% CI 94.4-99.2). The CCDSS definition had a sensitivity of 91.0% (95% CI 81.2-94.6), specificity of 99.0% (95% CI 96.4-99.9), PPV of 98.9% (95% CI 96.1-99.9), and NPV of 91.7% (95% CI 87.2-95.0). Using the more sensitive Marrie definition, the average annual adjusted incidence per 100,000 between 2001 and 2013 was 16.5 (95% CI 15.8-17.2), and the age- and sex-standardized prevalence of MS in Saskatchewan in 2013 was 313.6 per 100,000 (95% CI 303.0-324.3). Over the study period, incidence remained stable while prevalence increased slightly. Conclusion: We confirm Saskatchewan has one of the highest rates of MS in the world. Similar to other regions in Canada, incidence has remained stable while prevalence has gradually increased.

Background: Recent advances in neurophysiological techniques have contributed to our understanding of the pathophysiology of Huntington’s disease (HD). Studies of the motor cortical excitability and central motor pathways have shown variable results. Objectives: Our aims were to evaluate the cortical excitability changes in HD using transcranial magnetic stimulation (TMS) and correlate the changes with cognitive impairment. Methods: The study included 32 HD patients and 30 age- and gender-matched controls. The demographic and clinical profiles of the patients were recorded. All subjects were evaluated by TMS and resting motor threshold (RMT), central motor conduction time (CMCT), silent period (SP), short-interval intracortical inhibition (SICI), and intracortical facilitation were determined. A battery of neuropsychological tests was administered to all subjects. Results: The mean age of the patients was 42.1±14.1 years, and that of controls 39.4±12.4 years (p=0.61). There was no significant difference in RMT and CMCT between the two groups. There was a mild prolongation of the contralateral SP in HD, but it was not significant. SICI was significantly reduced in HD (p<0.0001). A significant impairment in attention, verbal fluency, executive function, visuospatial function, learning, and memory was observed in HD patients. However, there was no correlation between cortical excitability changes and cognitive impairment. Conclusions: TMS is a valuable method of evaluating cortical excitability changes in HD. These patients have reduced SICI and significant impairment of cognition in multiple domains.

Background: Caregivers are often unprepared and overwhelmed with the responsibilities of providing care to stroke survivors, which can lead to negative physical and psychological effects. Purpose: To evaluate the impact of the Family Informal Caregiver Stroke Self-Management (FICSS) program on burden and life changes resulting from providing care among family caregivers of stroke survivors. Methods: A prospective pre-test and post-test design using quantitative and qualitative data was used to evaluate the program with a convenience sample of 42 caregivers. The four-module facilitated program consisted of small group-guided discussion. Quantitative evaluations were completed at baseline, 2 weeks and 6 months (post-intervention), and qualitative data were collected at 2 weeks and 6 months. Life changes and burden were measured using the Bakas Caregiving Outcome Scale (BCOS) and the Oberst Caregiving Burden Scale (OCBS), respectively. Results: The BCOS scores increased consistently over time, showing significant differences at 6 months compared with 2 weeks (mean difference: 5.29, 95% confidence interval [CI]: 0.30-10.28, p=0.04) and baseline (mean difference: 7.58, 95% CI: 2.92-12.23, p=0.001). The OCBS time scores decreased consistently over time, showing a significant difference at 6 months compared with baseline (mean difference: −5.20, 95% CI: −0.96 to −9.44, p=0.02). The OCBS difficulty scores fluctuated over time, resulting in no overall difference from baseline to 6 months. Qualitative themes were consistent with the positive quantitative findings. Conclusion: Study results suggest that the FICSS program may result in reduced caregiver burden and improved life changes resulting from providing care.

Background: Pharmacists have become an integral member of the multidisciplinary team providing clinical patient care in various healthcare settings. Although evidence supporting their role in the care of patients with other disease states is well-established, minimal literature has been published evaluating pharmacist interventions in stroke patients. The purpose of this systematic review is to summarize the evidence evaluating the impact of pharmacist interventions on stroke patient outcomes. Methods: Study abstracts and full-text articles evaluating the impact of a pharmacist intervention on outcomes in patients with an acute stroke/transient ischemic attack (TIA) or a history of an acute stroke/TIA were identified and a qualitative analysis performed. Results: A total of 20 abstracts and full-text studies were included. The included studies provided evidence supporting pharmacist interventions in multiple settings, including emergency departments, inpatient, outpatient, and community pharmacy settings. In a significant proportion of the studies, pharmacist care was collaborative with other healthcare professionals. Some of the pharmacist interventions included participation in a stroke response team, assessment for thrombolytic use, medication reconciliation, participation in patient rounds, identification and resolution of drug therapy problems, risk-factor reduction, and patient education. Pharmacist involvement was associated with increased use of evidence-based therapies, medication adherence, risk-factor target achievement, and maintenance of health-related quality of life. Conclusions: Available evidence suggests that a variety of pharmacist interventions can have a positive impact on stroke patient outcomes. Pharmacists should be considered an integral member of the stroke patient care team.

Malignant gliomas (MG) are highly invasive and aggressive brain tumors. Despite the current standard of care, the prognosis for patients with MG is abysmal– highlighting the need for novel, more effective treatment options to combat this aggressive disease. Oncolytic virus (OV) therapy is an advancing treatment option that harnesses tumor-selective viruses to kill cancer cells while simultaneously facilitating a systemic anti-tumor immune response. Many studies have noted synergistic effects when OV’s are combined with radiotherapy in preclinical cancer models, warranting further investigation of this multi-modal approach. Image-guided radiotherapy (IGRT) uses computer-modulated imaging techniques to precisely deliver ionizing radiation to treat cancer. Despite the precision IGRT offers, cancer cells can still be ‘missed’ due to tumor microextensions or radioresistant cell populations– such as glioma stem cells or therapy-induced senescent cancer cells –and may contribute to recurrence or progression. Here we propose to combine our mCherry-tagged mutant vaccinia virus (deltaF4L-deltaJ2R-mCherry), which exhibits tumor-selectivity due to mutations in key viral nucleotide biosynthesis genes, with IGRT executed using state-of-the-art Small Animal Radiation Research Platform (SARRP) technology. We hypothesize that combining deltaF4L-deltaJ2R-mCherry with IGRT will produce better tumor control than either modality alone, by generating additive or synergistic effects in which IGRT destroys the majority of the tumor mass while our OV seeks out and targets any remaining cancer cells that have been missed or are resistant to radiotherapy.

Background: Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, spinal cord injury, or multiple sclerosis. These syndromes are much less common than peripheral etiologies, with less known regarding optimal treatment. The objective of this study was to determine the long-term clinical effectiveness of the management of central relative to peripheral neuropathic pain at tertiary pain centers. Methods: Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified from a prospective observational cohort from seven Canadian tertiary centers. Data regarding patient -characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome was the composite of reduced average pain intensity and pain interference. Secondary outcomes included assessments of function, mood, and quality-of-life. Results: At 12-month follow-up, 13.5% (95%CI,5.6-25.8) of patients achieved ≥30% reduction in pain, whereas 38.5% (95%CI,25.3-53.0) achieved a ≥1 point reduction in pain interference; 9.6% (95%CI,3.2-21.0) of patients achieving both these measures. Patients with peripheral neuropathic pain were more likely to achieve this primary outcome at 12-months (25.3% of patients; 95%CI,21.4-29.5) (p=.012). Conclusions: Patients with central neuropathic pain were less likely to achieve a meaningful improvement in pain and function compared to patients with peripheral neuropathic pain at 12-month follow-up.

Background: Non-invasive ventilation (NIV) improves quality of life and survival in patients with amyotrophic lateral sclerosis (ALS) and respiratory symptoms. Little is known about the patterns of NIV use over time and the impact of NIV on end-of-life decision-making in ALS. Objective: This study assessed the pattern of NIV use over the course of the disease and the timing of end-of-life discussions in people living with ALS. Method: A retrospective single-center cohort study was performed at London Health Sciences Centre. Daily NIV duration of use was evaluated at 3-month intervals. The timing of diagnosis, NIV initiation, discussions relating to do-not-attempt-resuscitation (DNAR) and death were examined. Results: In total, 48 patients were included in the analysis. Duration of NIV use increased over time, and tolerance to NIV was observed to be better than expected in patients with bulbar-onset ALS. There was a high degree of variability in the timing of end-of-life discussions in patients with ALS (356±451 days from diagnosis). In this cohort, there was a strong association between the timing of discussions regarding code status and establishment of a DNAR order (r2=0.93). Conclusion: This retrospective cohort study suggests that the use of NIV in ALS increases over time and that there remains a great deal of variability in the timing of end-of-life discussions in people living with ALS. Future prospective studies exploring the use NIV over the disease trajectory and how NIV affects end-of-life decision-making in people with ALS are needed.

Purpose: Exercise has been shown to be beneficial for the physical and psychological health of cancer survivors, however, little research has been conducted on the effects of exercise in the brain tumour population. Survivors with brain tumours present with unique challenges in terms of mobility and function that may compromise their ability to safety take part in community-based exercise. Methods: Three survivors with primary brain tumours will be profiled in this case series presentation. Participants were screened using a cancer specific intake questionnaire and the Physical Activity Readiness Questionnaire, and triaged to supervised clinic-based or community-based exercise. All participants completed the 12-week intervention for the Alberta Cancer Exercise (ACE) study. Measurements were taken at baseline, and post-intervention including measures of body composition, aerobic fitness, musculoskeletal fitness, balance and flexibility. Self-reported measures included questionnaires to assess impact on physical functioning, symptoms and quality of life, and to evaluate satisfaction with programming. Results: One participant was referred to supervised clinic-based exercise programming due to a high risk of falls, and two participants were deemed safe and approved for community-based supported exercise programming at a preferred location closer to their home. Preliminary results suggest high program satisfaction, maintenance and/or benefit of physical fitness, balance, and symptom control. Conclusions: Further efforts are needed to better tailor programming to the needs of the survivor and consideration given to the advantages of the supervised clinic-based environment when compared to the survivor preference for a “closer to home” community-based setting.

The objective of this study was to develop a shared-care model to enable primary-care physicians to participate more fully in meeting the complex, multidisciplinary healthcare needs of patients with multiple sclerosis (MS). Design: The design consisted of development of consensus recommendations and a shared-care algorithm. Participants: A working group of 11 Canadian neurologists involved in the management of patients with MS were included in this study. Main message: The clinical management of patients with multiple sclerosis is increasing in complexity as new disease-modifying therapies (DMTs) become available, and ongoing safety monitoring is required. A shared-care model that includes primary care physicians is needed. Primary care physicians can assist in the early detection of MS of individuals presenting with neurological symptoms. Additional key roles for family physicians are health promotion, symptom management, and safety and relapse monitoring of DMT-treated patients. General principles of health promotion include counseling MS patients on maintaining a healthy lifestyle; performing standard screening measures; and identifying and treating comorbidities. Of particular importance are depression and anxiety, which occur in >20% of MS patients. Standard work-ups and treatments are needed for common MS-related symptoms, such as fatigue, pain, bladder dysfunction, sexual dysfunction, spasticity, and sleep disorders. Ongoing safety monitoring is required for patients receiving specific DMTs. Multiple sclerosis medications are generally contraindicated during pregnancy, and patients should be counseled to practice effective contraception. Conclusions: Multiple sclerosis is a complex, disabling illness, which, similar to other chronic diseases, requires ongoing multidisciplinary care to meet the evolving needs of patients throughout the clinical course. Family physicians can play an invaluable role in maintaining general health, managing MS-related symptoms and comorbidities, monitoring for treatment-related adverse effects and MS relapses, and coordinating allied health services to ensure continuity of care to meet the complex and evolving needs of MS patients through the disease course. RÉSUMÉ:Élaborer un modèle de soins partagés dans les cas de sclérose en plaques récurrente-rémittente.Objectif: Élaborer un modèle de soins partagés afin de permettre aux médecins de première ligne de mieux répondre aux besoins complexes et multidisciplinaires de patients atteints de la sclérose en plaques (SP). Conception : Recommandations résultant d’un consensus et élaboration d’un algorithme en matière de soins partagés. Participants : Un groupe de travail formé de onze neurologues canadiens impliqués dans la prise en charge de patients atteints de la SP. Message-clé : La prise en charge clinique de patients atteints de la SP est de plus en plus complexe dans la mesure où des médicaments modificateurs de l’évolution de la maladie (MMSP) deviennent accessibles et où un suivi permanent en matière de sécurité est nécessaire. Soulignons aussi qu’un modèle de soins partagés incluant les médecins de première ligne est nécessaire. Ces professionnels peuvent permettre un dépistage plus rapide de la SP chez des individus présentant des symptômes neurologiques. Ils peuvent aussi jouer un rôle de premier plan en matière de promotion de la santé, de soulagement des symptômes et de suivi de patients traités avec des MMSP en ce qui a trait à leur sécurité et à de possibles rechutes. Parmi les principes généraux de promotion de la santé, on peut inclure les suivants : offrir aux patients atteints de la SP des conseils leur permettant de maintenir de saines habitudes de vie ; adopter des mesures de dépistage standards ; identifier et traiter les comorbidités. À cet égard, l’anxiété et la dépression sont d’une importance particulière et sont fréquemment signalées (> 20 %) chez les patients atteints de SP. Des démarches d’investigation et des traitements standards sont nécessaires dans le cas des symptômes courants reliés à la SP, par exemple de la fatigue, des douleurs, une dysfonction vésicale, des dysfonctions sexuelles, de la spasticité et des troubles du sommeil. On l’a dit, un suivi permanent s’impose dans le cas de patients bénéficiant d’un traitement spécifique avec des MMSP. Les médicaments associés à la SP sont généralement contre-indiqués durant la grossesse de sorte qu’on devrait conseiller aux patients d’adopter des méthodes de contraception efficaces. Conclusions : La SP est une maladie complexe et invalidante qui, à l’instar d’autres maladies chroniques, exige des soins multidisciplinaires continus afin de répondre, en lien avec un tableau clinique précis, aux besoins en constante évolution des patients. Les médecins de première ligne peuvent jouer un rôle irremplaçable à plusieurs égards : dans le maintien d’une bonne santé ; le suivi et le soulagement des symptômes et des comorbidités reliés à la SP ; le suivi des rechutes et des effets indésirables associés aux traitements. N’oublions pas non plus la coordination des services paramédicaux afin d’assurer, durant l’évolution de la SP, une continuité des soins répondant aux besoins complexes et en constante évolution des patients atteints de cette maladie.

Background: A need exists to characterise the long-term cognitive outcomes in patients who recovered from autoimmune encephalitis and to identify the modifiable factors associated with improved outcomes. Methods: We retrospectively analysed data from patients diagnosed with autoimmune encephalitis in our outpatient autoimmune encephalitis clinic over a 5-year period, where the Montreal Cognitive Assessment (MoCA) is routinely administered. Results: In total, 21 patients met the inclusion criteria, of whom 52% had persistent cognitive impairment at their latest follow-up (median delay to testing=20 months, range 13-182). Visuospatial and executive abilities, language, attention, and delayed recall were predominantly affected. Patients with status epilepticus at presentation had lower total MoCA scores at their last follow-up (median total score 21, range 15-29) compared with patients without status epilepticus at presentation (median total score 27.5, range 21-30; r2=0.366, p=0.004). Patients who experienced delays of more than 60 days from symptom onset to initiation of treatment (either immunosuppression or tumour removal) were more likely to have a MoCA score compatible with cognitive impairment at their last follow-up (r2=0.253, p=0.0239; z-score=−2.01, p=0.044). Conclusions: Our study suggests that the MoCA may be used to evaluate cognition in recovering patients with autoimmune encephalitis. Delays to treatment shorter than 60 days and absence of status epilepticus at onset were associated with better performance on the MoCA obtained more than 1 year after symptom onset, and may predict better long-term cognitive outcomes.

Background: Post-stroke depression (PSD) is the most frequent psychiatric complication following ischemic stroke. It affects up to 60% of all patients and is associated with increased morbidity and mortality following ischemic stroke. The pathophysiology of PSD remains elusive and appears to be multifactorial, rather than “purely” biological or psychosocial in origin. Thus, valid animal models of PSD would contribute to the study of the etiology (and treatment) of this disorder. Methods: The present study depicts a rat model for PSD, using middle cerebral artery occlusion (MCAO). The two-way shuttle avoidance task, Porsolt forced-swim test, and sucrose preference test were employed to assess any depression-like behavior. Localized brain expressions of brain-derived neurotrophic factor (BDNF) protein levels were evaluated to examine the possible involvement of the brain neuronal plasticity in the observed behavioral syndrome. The raw data were subjected to unsupervised fuzzy clustering (UFC) algorithms to assess the sensitivity of bio-behavioral measures indicative of depressive symptoms post MCAO. Results: About 56% of the rats developed significant depressive-like behavioral disruptions as a result of MCAO compared with 4% in the sham-operated control rats. A pattern of a depressive-like behavioral response was common to all affected MCAO animals, characterized by significantly more escape failures and reduced number of total avoidance shuttles, a significant elevation in immobility duration, and reduced sucrose preference. Significant downregulations of BDNF protein levels in the hippocampal sub-regions, frontal cortex, and hypothalamus were observed in all affected MCAO animals. Conclusion: The UFC analysis supports the behavioral analysis and thus, lends validity to our results.

Background: Parkinson’s disease (PD) is a degenerative disorder of the central nervous system mainly affecting the motor system. Presently, there is no effective and safe drug to treat patients with PD. Ginkgo biloba extract (GBE), obtained from leaves of the Ginkgo biloba tree, is a complex mixture of ingredients primarily containing two active components: flavonoids and terpenoids. In this study, we investigated the effects of GBE on A53T α-synuclein transgenic mice, a PD model that has better simulated the progression of PD patients than other models such as the 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine–induced PD model. Methods: Fifty α-synuclein A53T transgenic mice were fed and treated with GBE, and locomotor activity was detected by pole test, forced swim test, and wire-hang test. The expression of tyrosine hydroxylase and dopamine transporters was detected using immunohistochemistry. Superoxide dismutase activity, glutathione peroxidase activity, and malondialdehyde expression were detected using an assay kit. Results: Our results show that GBE treatment improved locomotor activity and that superoxide dismutase and glutathione peroxidase inhibited the expression of methane dicarboxylic aldehyde and recovered the expression of tyrosine hydroxylase and dopamine transporters. Conclusions: The GBE treatment improved locomotor activity and inhibited the development of PD in the A53T α-synuclein transgenic mice, which may be partly responsible for decreased oxidative damage and maintain the normal dopamine homeostasis.

Background: Bevacizumab has been used in recurrent glioblastoma (rGBM) since 2010 in Canada. Given its cost, potential toxicities, and unclear efficacy, further studies are required to better define suitable candidates for therapy. Methods: A single-center retrospective review of patients started on bevacizumab for rGBM from 2012 to 2015 was performed. Patient demographics, tumor characteristics, treatment regimen, and dates of clinical progression and death were collected. Overall survival (OS) and progression-free survival (PFS) were used as clinical outcomes and estimates. Radiological response was assessed using modified Response Assessment in Neuro-Oncology criteria. Results: A total of 80 patients were included. There were 67 reported deaths, and the median OS was 9.2 months (95% confidence interval [CI95%]=7.0-10.1 months), with a 12-month OS of 31% (CI95%=21.9-43.5%). Some 79 patients were included for analysis of clinical progression, among whom 61 had documented clinical progression. The median clinical PFS was 4.6 months (CI95%=3.8-6.4 months), and the 6-month clinical PFS was 39% (CI95%=29.0-52.9%). Addition of chemotherapy did not improve clinical outcomes. A total of 68 patients were included for radiological progression analysis, with 58 radiological progressions. The median radiological PFS was 5.8 months (CI95%=4.2-6.7 months), and the 6-month radiological PFS was 46% (CI95%=35.6-60.0%). Conclusions: This is the first reported Canadian experience with bevacizumab for rGBM. Our clinical outcomes are consistent with published data from multicenter phase II and III trials on bevacizumab in rGBM. More research is required to determine which subtype(s) of patients with rGBM could benefit from bevacizumab upon recurrence.

By contrast to infantile spinal muscular atrophy, which usually links to deletions in the SMN genes, fetal onset motor neuron disease is poorly reported. We collected a series of twelve cases of fetal arthrogryposis (16-31 weeks gestational age) with fetal motor neuron disease and excluded infectious diseases, lysosomal storage disease and neuroaxonal dystrophy. Of these twelve, 3 were thought to be ischemic in nature with microvascular alterations and systemic or central nervous system ischemic injury. The remaining 9 all displayed marked reduction in anterior horn motor neurons. Of these 9, four demonstrated mineralised neurons, four demonstrated either neuronal loss or cavitation in the globus pallidus, and in two, degenerating neurons were detectable in the brainstem or globus pallidus. Specific sequencing of SMN1 was performed in 6 of 9 and was reported as normal. Whole exome sequencing was performed in 4 without definitive diagnosis. We conclude that fetal motor neuron disease can be distinguished from ischemic injury, is morphologically heterogeneous, may affect the globus pallidus and is rarely linked to SMN1 mutations.