We examined functional outcomes and quality of life of whole brain radiotherapy (WBRT) with integrated fractionated stereotactic radiotherapy boost (FSRT) for brain metastases treatment. Methods Eighty seven people with 1-3 brain metastases were enrolled on this Phase II trial of WBRT (30Gy/10)+simultaneous FSRT, (60Gy/10). Results Mean (Min-Max) baseline KPS, Mini Mental Status Exam (MMSE) and FACT-BR quality of life were 83 (70-100), 28 (21-30) and 143 (98-153). Lower baseline MMSE (but not KPS or FACT-Br) was associated with worse survival after adjusting for age, number of metastases, primary and extra-cranial disease status. Crude rates of deterioration (>10 points decrease from baseline for KPS and FACT-Br, MMSE fall to<27) ranged from 26-38% for KPS, 32-59% for FACT-Br and 0-16%for MMSE depending on the time-point assessed with higher rates generally noted at earlier time points (<6months post-treatment). Using a linear mixed models analysis, significant declines from baseline were noted for KPS and FACT-Br (largest effects at 6 weeks to 3 months) with no significant change in MMSE. Conclusions The effects on function and quality of life of this integrated treatment of WBRT+simultaneous FSRT were similar to other published series combining WBRT+SRS.

To understand physician preferences and bleeding complication rates of intramuscular botulinum neurotoxin type A injections for spasticity management in anticoagulated patients, questionnaires were mailed to 138 physicians across Canada. The international normalized ratio comfort range for injections was <2.0 in 10%, 2.0 to 2.5 in 35%, 2.6 to 3.0 in 25%, and 3.1 to 3.5 in 20% of physicians. Only 23% injected outside their comfort value and 57% did not; 72% did not normalize the international normalized ratio value before injections. Only one injector reported the development of compartment syndrome. As expected, high variability exists in physician preferences in botulinum neurotoxin type A injection in anticoagulated patients.

Background: The ketogenic diet (KD) is used to treat severe childhood-onset epileptic encephalopathies, such as Infantile Spasms (IS). Unfortunately, limited resources for KD initiation result in treatment delays. We ask if earlier KD treatment of early-onset drug-resistant epilepsy results in better seizure outcomes. Methods: Children who started KD before age 4 years between 2000-present at SickKids Hospital were identified. Six-month seizure outcome was calculated as percent of pre-diet baseline seizure frequency (BSF). Results: 67 children were identified. 30 (44.8%) started KD <2 years old, 37 (55.2%) started KD 2-4 years old. Among <2 years old group, 83.3% achieved 50% reduction in BSF and 36.7% achieved 90% reduction. Among 2-4 year old group, 62.2% achieved 50% reduction in BSF and 24.3% achieved 90% reduction. 38 children had a history of IS; 17 with IS at diet initiation and 21 with past history of IS. 41.2% of the spasms cohort achieved 90% reduction in BSF, compared to 23.8% of the post-spasms cohort. Conclusions: KD was more effective when started before age 2 years than 2-4 years, and more effective in children with IS than in children with past history of IS. A rapid protocol for KD initiation in young infants and children may improve long-term outcomes

John F. MacDonald was a close friend and mentor whose life was ended far too soon on April 22, 2014. To those who knew him, John was an endearing blend of fiery Scotsman, compassionate socialist, dedicated family man, and tireless investigator. Those close to him valued his loyalty and friendship, relished his biting wit, and puzzled at his self-deprecating manner. His career spanned a remarkable period of discovery from the early identification of excitatory amino acid, to the molecular cloning and characterization of glutamate receptors and the elucidation of mechanisms responsible for regulating their function. A true pioneer in each of these areas, John’s research has had a lasting impact on our understanding of excitatory synaptic transmission and its plasticity. Our intent in commemorating John’s work is to focus on some notable discoveries that highlight the impact and innovative aspects of John’s work. In doing so, we also wish to highlight just how greatly our understanding of the glutamate transmitter systems has advanced since the late 1970s, when John first launched his independent neuroscience career.

Background: Sturge Weber Syndrome (SWS) patients at risk of epilepsy are often not identified before their first seizure which leads to unnecessary follow up of many patients with facial angioma. Methods: The medical photography database of our institution has been reviewed to identify SWS patients followed between 1993 and 2013. Patients with isolated glaucoma were compared to patients with epilepsy regarding the location of the facial angioma, the presence of asymmetrical background activity on EEG done prior epilepsy onset and cerebral imaging. Logistical regression tests and a p-value of 0.05 were used. Results: 21 patients with SWS have been identified. No significant difference was noted when patients were compared based on the laterality of the lesion (p=0.169), or the location of the facial angioma (p = 0.314 to 0.999). Only 2 epileptic patients had digital EEG done prior the onset of epilepsy and only 2 patients with glaucoma had digital EEG done during their follow up. No significant difference was noted between EEG background activities in the two groups (p= 0.514). The presence of venous drainage anomalies (VDA) predicted (p = 0.004) the onset of epilepsy. Conclusions: Cerebral VDA increases the risk of epilepsy in SWS patients. Since they can be detected at birth, they might guide the management.

Background: A large proportion of people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) suffer from neurocognitive impairment (NCI). The causes of the NCI are multifold in HIV infection although a subset of HIV/AIDS patients are affected by the spectrum syndrome, HIV-associated neurocognitive disorder (HAND). We investigated the Montreal Cognitive Assessment (MoCA) in relation to clinical, demographic and laboratory findings as well as its ability to predict symptomatic HAND (sHAND) among patients with HIV/AIDS. Methods: All subjects were receiving regular HIV care including CD4+ T cell counts, plasma viral load measurements, clinical evaluations and antiretroviral therapy. The diagnosis of sHAND was based upon clinical, neuroimaging, and neuropsychological assessments.Results: Among HIV-1 seropositive subjects (n=125), ethnicity, education and employment were positively correlated with their MoCA scores (p<0.05). In contrast, polypharmacy, central nervous system penetration-effectiveness (CPE) score, antiretroviral drug exposure, substance use and nucleoside/nucleotide reverse transcriptase inhibitor side effects were negatively correlated with MoCA scores (p<0.05). Of note, MoCA scores were not associated with CD4 T cell nadir levels, age, peak viral load, or veterans aging cohort study index. In subjects with or without sHAND, mean MoCA scores differed (sHAND, 22.8±3.51; non-HAND 25.2±2.64) (p<0.05) with a receiver operating characteristic curve showing an area under curve of 0.71 and an optimal MoCA cut-off value of 23.5 when compared to the established diagnostic paradigm. Conclusions: MoCA scores were generally lower in this HIV/AIDS population compared to reported scores in the general population. MoCA performance was associated with multiple clinical variables but displayed limited predictive utility in detecting sHAND.

The purpose of this study was to investigate the impact of an intervention designed to support newly diagnosed primary brain tumour patients. The intervention involved a structured, one time meeting between newly diagnosed patients and trained volunteer “veteran” primary brain tumour patients. Methods Two trained volunteers met for a single, face to face meeting on an individual basis with a total of 10 newly diagnosed patients. A combination of questionnaires and interviews were used to investigate the impact of the intervention for the new patients and the volunteers. Results: The intervention appeared to be of substantial value for both groups of participants. Analysis revealed that the newly diagnosed patients experienced a range of benefits, including those related to the themes of: increased hope; valued guidance; hearing what it’s really like; overcoming aloneness; and realignment of priorities. Veteran patients experienced a sense accomplishment and decreased anxiety as a result of the intervention. Only minor adverse effects and challenges were reported. Conclusions The findings provide initial evidence that the experimental intervention has the potential to be a safe, effective means of promoting psycho-social well-being in newly diagnosed patients and may also have positive effects for veteran patients. Further investigation into the use of one to one, peer support for brain tumour patients is an important research priority.

Background: The muscular dystrophies are a heterogeneous group of genetic muscle diseases with variable distribution of weakness and mode of inheritance.Methods: We previously performed a systematic review of worldwide population-based studies on Duchenne and Becker muscular dystrophies; the current study focused on the epidemiology of other muscular dystrophies using Medline and EMBASE databases. Two reviewers independently reviewed all abstracts, full-text articles, and abstracted data from 1985 to 2011. Pooling of prevalence estimates was performed using random-effect models.Results: A total of 1104 abstracts and 167 full-text articles were reviewed. Thirty-one studies met all eligibility criteria and were included in the final analysis. The overall pooled prevalence of combined muscular dystrophies was 16.14 (confidence interval [CI], 11.21-23.23) per 100,000. The prevalence estimates per 100,000 were 8.26 (CI, 4.99-13.68) for myotonic dystrophy, 3.95 (CI, 2.89-5.40) for facioscapulohumeral dystrophy, 1.63 (CI, 0.94-2.81) for limb girdle muscular dystrophy, and 0.99 (CI, 0.62-1.57) for congenital muscular dystrophies.Conclusions: The studies differed widely in their approaches to case ascertainment, and substantial gaps remain in the global estimates of many other types of muscular dystrophies. Additional epidemiological studies using standardized diagnostic criteria as well as multiple sources of case ascertainment will help address the economic impact and health care burden of muscular dystrophies worldwide.

Background: Down syndrome (DS) is the primary genetic cause of mental retardation and seizures are present in an estimated 5-13% of cases. One-third of seizures in DS are infantile spasms (IS). Hypsarrythmia (HS) is the cardinal electroencephalogram (EEG) feature of IS and has been found to affect cognition; however, its effect on DS patients is inconclusively reported. This study assesses the correlation of HS with cognitive outcomes in DS using the largest sample size to date. Methods: Retrospective study of medical records of children with DS [0-18yrs] at SickKids Hospital in Toronto, from 1990-2013. Seizure history, EEG findings, comorbities, and pharmacological treatments were identified. Developmental outcomes were also assessed from physician comments on motor, verbal and cognitive abilities. The cognitive outcomes of DS patients with and without HS were compared. Results: 70 [male=40] patients with DS and seizures were included. Among 31 (44.2%) patients with DS and IS, 27 had HS. Chi-square analysis showed a significant difference [P=0.007] in prevalence of severe developmental delay in patients with IS and HS versus all other seizure types. Conclusions: The developmental outcome of patients with Down syndrome appears to worsen when IS and HS had occurred in the first year of life.