bluuebunny/crossref_metadata_2025 huggingface dataset:
Frontal Assessment Battery to Evaluate Frontal Lobe Dysfunction in ALS Patients
Authors: Ahn Suk-Won , Kim Su-Hyun , Kim Jee-Eun , Kim Sung-Min , Kim Seung Hyun , Sung Jung-Joon , Lee Kwang-Woo , Hong Yoon-Ho
Published: December 2014

Background:

Assessment of frontal lobe impairment in amyotrophic lateral sclerosis (ALS) is a matter of great importance, since it often causes ALS patients to decrease medication and nursing compliance, thus shortening their survival time.

Methods:

The frontal assessment battery (FAB) is a short and rapid method for assessing frontal executive functions. We investigated the applicability of the FAB as a screening method for assessing cognitive impairments in 61 ALS patients. Depending on the results of the FAB, we classified patients into two subgroups: FAB-normal and FAB-abnormal. We then performed additional evaluations of cognitive function using the Korean version of the mini-mental state examination (K-MMSE), a verbal fluency test (COWAT), and a neuropsychiatric inventory (NPI). Results of these tests were compared between the two groups using Mann-Whitney U-tests, and Spearman correlation analyses were used to investigate the relationships between FAB score and disease duration and severity.

Results:

Of the 61 sporadic ALS patients included in this study, 14 were classified as FAB-abnormal and 47 were classified as FAB-normal. The FAB-normal and FAB-abnormal patients performed significantly differently in all domains of the COWAT. There was no difference in behavioral disturbance, as assessed by the NPI, between the two groups. The FAB scores were found to significantly correlate with both disease duration and severity.

Conclusions:

The FAB shows promise as a method of screening for frontal lobe dysfunction in ALS, as it is not only quick and easy, but also reliable. Additional studies should examine how FAB performance changes as ALS progresses.
Early Treatment of a Progressive Rasmussen's Like Syndrome with Ganciclovir
Authors: McLachlan Richard S. , Diosy David , Levin Simon
Published: December 2014

Background:

Escalating focal sensorimotor seizures, progressive neurologic deficit and cognitive decline with associated typical magnetic resonance imaging (MRI) findings or pathological confirmation constitute the syndrome of Rasmussen's encephalitis.

Methods:

Three patients with this clinical scenario had long-term follow-up after being given the antiviral drug ganciclovir 10 mg/kg/day IV for ten days within one to three months of disease onset.

Results:

Seizures occurred at least hourly and were localized to the Rolandic region. The MRIs were normal in one patient and in two showed changes consistent with ongoing seizures. Two patients, one whose short-term outcome was reported previously, had immediate and sustained cessation of seizures and resolution of their neurologic deficit. One patient with seizures from both hemispheres did not respond and went on to hemispherectomy that confirmed chronic encephalitis. Seizures continued in five other patients treated 6 to 72 months after disease onset.

Conclusion:

The sustained seizure control after ganciclovir in two of three patients suggests this drug may be effective when given early in the course of this subacute intractable focal epilepsy syndrome.
Susac's Syndrome
Authors: Lian Kevin , Siripurapu Rekha , Yeung Robert , Hopyan Julia , Eng Kenneth T. , Aviv Richard I. , Symons Sean P.
Published: December 2014

A 40-year-old woman with no significant previous medical history presented with a three month history of ataxia, confusion, memory difficulties, and headaches. Physical examination revealed numbness in the left hand, but was otherwise unremarkable. Magnetic resonance imaging fluid-attenuated inversion recovery (MRI FLAIR) images demonstrated multiple small white matter hyperintensities, including lesions involving the corpus callosum. There were also deep gray nuclei lesions (Figure 1). The corpus callosum lesions involved the central fibers (Figure 2). Post gadolinium T1 images demonstrated enhancement of some of the lesions as well as extensive perivascular and leptomeningeal enhancement (Figure 3). Extensive infectious serology, autoimmune panel, and paraneoplastic antibodies were negative. Lumbar puncture revealed elevated protein (1116 mg/L), but was otherwise normal. Brain biopsy indicated no apparent pathology. The patient was tentatively diagnosed with acute encephalopathy and treated with high dose steroids seven days after presentation. She was subsequently discharged and was sent for rehabilitation.
Adherence to Multiple Sclerosis Disease-Modifying Therapies in Ontario is Low
Authors: Wong Janice , Gomes Tara , Mamdani Muhammad , Manno Michael , O'Connor Paul W.
Published: December 2014

Background/Objective:

Differences in patient adherence to various disease-modifying drugs (DMDs) in the treatment of multiple sclerosis (MS) are not well understood. The goal of this study was to evaluate adherence of adult MS patients in Ontario with public drug plan coverage to various DMDs: intramuscular interferon beta-1a (i.m. IFNβ-1a, Avonex), subcutaneous interferon beta-1a (s.c. IFNβ-1a, Rebif), subcutaneous interferon beta-1b (IFNβ-1b, Betaseron) or glatiramer acetate (Copaxone).

Methods:

In this retrospective cohort study, Ontario Public Drug Plan beneficiaries aged 15 or older who were newly treated with i.m. IFNβ-1a, s.c. IFNβ-1a, IFNβ-1b or glatiramer acetate between April 2006 and March 2008 were followed forward until treatment discontinuation, switch to another DMD or a maximum two year follow-up period. Cumulative persistence rates were analyzed by the Kaplan-Meier method. The proportion of patients reaching the study endpoints after the two year follow-up period was also calculated.

Results:

Cumulative persistence rates for all four DMDs were similar over time (p=0.80), ranging from 73.6-79.1% at six months, 59.1-63.1% at one year and 41.5-47.4% at two years. After two years, the proportion of patients who had discontinued treatment, switched to another DMD or died was similar among DMDs (p=0.79, Fisher's exact test). Switching between DMD types was low and occurred in 3.4-6.5% of new DMD users.

Conclusions:

Adherence to DMDs in adult MS patients in Ontario is poor, which is consistent with previously reported adherence rates to MS DMDs in other regions. No significant differences in adherence exist between the DMDs evaluated in this study.
Lumbar Microdiscectomy: A Clinicoradiological Analysis of Outcome
Authors: Rahme Ralph , Moussa Ronald , Bou-Nassif Rabih , Maarrawi Joseph , Rizk Tony , Nohra Georges , Samaha Elie , Okais Nabil
Published: December 2014

Background:

The long-term outcome after lumbar microdiscectomy (LMD) may be affected by low back pain (LBP) and segmental instability, the determinants of which remain unclear. We sought to analyze the interaction between clinical, functional, and radiological variables and their impact on patient outcome.

Methods:

All patients who underwent LMD in 2004-2005 were invited to participate in this retrospective cohort study. Patients were re-evaluated clinically and radiologically after a three to five year follow-up.

Results:

Forty-one of 97 eligible patients were enrolled. Twelve patients (29.3%) reported moderate-to-severe sciatica, 12 (29.3%) had moderate LBP, and 13 (31.7%) exhibited clinical evidence of segmental instability. Thirty-eight patients (92.7%) had minimal disability and 3 (7.3%) had moderate disability. Twenty-three patients (56.1%) were fully satisfied, while 18 (43.9%) had only partial satisfaction, having expected a better outcome. Thirty-three patients (80.5%) returned to full-time work. Median disc space collapse (DSC) was 20% (range 5-66%) and L4-L5 was particularly affected. Prevalence of Modic changes increased from 46.3% to 78% with type 2 predominance. Multivariate logistic regression analysis identified the following negative prognostic factors: female sex, young age, lack of regular exercise, and chronic preoperative LBP. There was no correlation between the course of Modic changes, DSC, and patient outcome.

Conclusion:

Although many patients may be symptomatic following LMD, significant disability and dissatisfaction are uncommon. Female sex, young age, lack of exercise, and chronic preoperative LBP may predict a worse outcome. Disc collapse is a universal finding, particularly at L4-L5. Neither DSC nor Modic changes seem to affect patient outcome.
Pain Management in Post-Craniotomy Patients: A Survey of Canadian Neurosurgeons
Authors: Hassouneh Basil , Centofanti John E. , Reddy Kesava
Published: December 2014

Introduction:

Despite the growing recognition for analgesic needs in post-craniotomy patients, this remains a poorly studied area in neurological surgery. The class and regimen of analgesia that is most suitable for these patients remains controversial. The objective of this study is to examine the current beliefs and practices of Canadian neurosurgeons when managing post-craniotomy pain.

Methods:

A survey was sent to all practicing Canadian neurosurgeons to examine the following aspects of analgesia in craniotomy patients: type of analgesics used, common side effects encountered, satisfaction with current regimen and the rationale for their practice.

Results:

Of 156 potential respondents, 103 neurosurgeons (66%) completed the survey. Codeine (59%) was the most prescribed firstline analgesic followed by morphine (38%). The use of a second-line opioid was significantly higher among codeine prescribers compared to morphine, 53% compared to 28% (p < 0.001). Nausea, constipation and neurologic depression were reported as common side effects by 76%, 66% and 27% of respondents respectively. Of the respondents, 90% reported a high level of satisfaction with their current choice of analgesia; nonetheless, they predominantly described their practice as personal preference or protocol driven rather than evidence-based.

Conclusions:

Codeine - a weak opioid - is the most common first-line analgesic prescribed to craniotomy patients. This practice is associated with substantially increased reliance on potent opioids for rescue analgesia. Whether novel regimens can provide optimal pain control while minimizing neurologic and gastrointestinal side effects remains to be addressed by future trials.
Tauopathies: One Disease or Many?
Authors: Bouchard Manon , Suchowersky Oksana
Published: December 2014

Tauopathies are a group of disorders that have in common abnormal accumulation of tau protein in the brain. Although the different tauopathies have long been considered to be separate diseases, it is now clear that progressive supranuclear palsy, corticobasal degeneration and some forms of tau-positive frontotemporal lobar degeneration share clinical, pathological and genetic features. The important overlap between these disorders suggest they may represent different phenotypes of a single disease process, the clinical result depending on the topography of pathological lesions as well as other unknown factors.
Gastrointestinal Symptoms in Parkinson Disease: Clinical Aspects and Management
Authors: Salat-Foix D. , Andrews C. N. , Meddings J. , Suchowersky O.
Published: December 2014

Although it is now generally recognized that the clinical spectrum of Parkinson disease (PD) is broader than its defining motor aspects, its various non-motor symptoms are often not routinely assessed in the clinical setting. As most of these symptoms are amenable to treatment, improved recognition would lead to more comprehensive management of the disease, and ultimately improve the quality of life for PD patients. In an attempt to increase the general awareness of physicians caring for these patients, this article focuses on the clinical manifestations and treatment of the gastrointestinal symptoms most commonly experienced by PD patients, as well as on the gastrointestinal side effects of antiparkinsonian treatments.
Monoclonal Antibodies and Progressive Multifocal Leukoencephalopathy
Authors: Keene Daniel L. , Legare Carole , Taylor Elaine , Gallivan Jim , Cawthorn Gloria Mah , Vu Duc
Published: December 2014

Monoclonal antibodies have become an important treatment option for a number of serious conditions. Concerns have arisen about the potential association of these products with progressive multifocal leukoencephalopathy (PML). A list of monoclonal antibodies authorized for sale was derived from the Health Canada Drug Product Database. Case reports of PML after exposure to a monoclonal antibody authorized for use in Canada were retrieved by searching Canada Vigilance and WHO adverse event databases and through a Pub MED/Medline literature search. 182 adverse event case reports were retrieved (adalimumab -1 case, alemtuzumab-14, bevacizumab -3, cetuximab -1, efalizumab - 8, ibritumomab tiuxetan-5, infliximab-4, natalizumab-32, and rituximab-114). The Canadian Product Monographs for natalizumab and ritiximab contain box warnings for PML. A natalizumab registry has been established.
ERK5: A Novel IKKα-Kinase in Rat Hippocampal Neurons
Authors: Goalstone Marc L.
Published: December 2014

Background:

Alzheimer's Disease (AD) is characterized in part by the increased presence of neurofibrillary tangles and amyloid beta (Aβ) plaques. Alzheimer's Disease is considered an inflammatory disease and, as such, nuclear factor-kappaB (NFκB) plays an important role in the pathophysiology of AD. Insulin acts as a neurotrophic factor. Yet, in the context of insulin resistance, concomitant hyperinsulinemia may contribute to the pathogenesis of AD.

Methods:

Rat Primmary Hippocampal Neurons (RPHN) were treated with insulin in the absence and presence of Wortmannin and ERK5 small inhibitory RNA and assayed for downstream effectors of activated ERK5.

Results:

Here we demonstrate that genetic inhibition of ERK5 blocks insulin stimulated (1) activation and translocation of ERK5 and NFκB, (2) phosphorylation of IKKα via association with ERK5, (3) increases in Aβ1-40 and Aβ1-42 soluble proteins 3-fold and 2.2-fold, respectively, and (4) increases in tau phosphorylation in RPHN.

Conclusions:

ERK5 plays an active role in insulin signaling in neurons and may be a potential therapeutic target for neurodegenerative diseases.
Causes for Treatment Delays in Dystonia and Hemifacial Spasm: A Canadian Survey
Authors: Jog Mandar , Chouinard Sylvain , Hobson Doug , Grimes David , Chen Robert , Bhogal Meetu , Simonyi Susan
Published: December 2014

Background:

Dystonia must be accurately diagnosed so that treatment can be administered promptly. However, dystonia is a complex disorder, with variable presentation, which can delay diagnosis.

Methods:

Data were gathered by questionnaire from 866 patients with dystonia or hemifacial spasm (HFS) treated in 14 movement disorders centres in Canada injecting botulinum toxin, to better understand the path to diagnosis, wait times and obstacles to treatment.

Results:

Most participants were female (64.1%), mean age was 58 years, and patients consulted an average of 3.2 physicians before receiving a dystonia or HFS diagnosis. Many patients (34%) received other diagnoses before referral to a movement disorders clinic, most commonly “stress” (42.7%). A variety of treatments were often received without a diagnosis. The mean lag time between symptom onset and diagnosis was 5.4 years. After the decision to use botulinum toxin, patients waited a mean of 3.1 months before treatment. The most common diagnoses were cervical dystonia (51.6% of patients), HFS (20.0%) and blepharospasm (9.8%).

Conclusions:

Survey results show that diagnosis of dystonias or of HFS, and therefore, access to treatment, is delayed. An educational program for primary care physicians may be helpful to decrease the time to diagnosis and referral to a specialist centre for treatment.
Stroke Rehabilitation in Ontario: An Opportunity for Health Care Transformation
Authors: Meyer Matthew J , Meyer John P , Foley Norine , Salter Katherine , McClure J Andrew , Teasell Robert
Published: December 2014

In this article, Ontario's stroke rehabilitation system is used to exemplify the challenges faced by rehabilitation and healthcare systems across Canada who are attempting to provide quality care to patients in the face of increasing demands. Currently, Ontario's rehabilitation system struggles in its efforts to provide accessible and comprehensive care to patients recovering from stroke. We begin our exploration by identifying both the primary stakeholders and the underlying factors that have contributed to the current challenges. The framework put forward in the Canadian Medical Association's recommendations for transformation is then used to suggest a vision for a more patient-focused system incorporating three key principles: a broader perspective, a patient-first approach, and greater unity. The use of health information technology, proper incentives, and greater accountability are discussed as mechanisms to improve the quality and efficiency of care.
E-Selectin Expression Increased in Human Ruptured Cerebral Aneurysm Tissues
Authors: Jia Wenqing , Wang Rong , Zhao Jizong , Liu Isabelle Yisha , Zhang Dong , Wang Xuejiang , Han Xiaodi
Published: December 2014

Objectives:

The purpose of the present study is to investigate the expression of inflammation factor endothelial-leukocyte adhesion molecule (E-selectin, CD62E) in cerebral aneurysm walls and its relationship with aneurysm rupture.

Methods:

Cerebral aneurysm tissue samples were collected at the time of surgical clipping of nine patients with history of subarachnoid hemorrhage, and then compared with control artery tissues from the superficial temporal arteries (STA) of five patients with intracranial tumors. Immunohistochemistry (IHC) was performed to reveal and localize E-selectin expression in the aneurysms and artery tissues. Western blot analysis was used to relatively quantify the level of E-selectine protein expression in cerebral aneurysms when compared with normal arteries.

Results:

E-selectin was detected in the wall of all the aneurysm tissue samples and was rarely found in normal control arteries by IHC, and it was concentrated in proliferating and disorganized epithelia cells. Moreover, with the Western blot method, the E-selectin protein level increased significantly in aneurysm tissues compared to normal STA.

Conclusions:

E-selectin might be an important factor involved in the process of cerebral aneurysm formation and rupture, by promoting inflammation and weakening cerebral artery walls.
TGF-beta 1 Codon 10 Polymorphism is Associated with Cerebral SVD
Authors: Tao Hong-miao , Chen Guo-zhong , Lu Xiao-dong , Hu Xiao-gang , Chen Gan-ping , Shao Bei
Published: December 2014

Background:

To clarify the role of inflammation in the pathogenesis of cerebral small vessel disease (SVD), we investigated whether the gene encoding transforming growth factor-beta 1(TGF-beta 1) is a risk factor for cerebral SVD as a whole, and for two different SVD subtypes.

Methods:

TGF-beta 1 codon10 (T+29C) genotype was determined in 441 Chinese patients (313 male and 128 female) with cerebral SVD and 450 control subjects (326 male and 124 female). Cerebral SVD patients were retrospectively classified into two groups based on neuroimaging findings: lacunar infarction group with 112 patients and ischaemic leukoaraiosis group with 329 patients.

Results:

Subjects carrying TT homozygote were susceptible to cerebral SVD [adjusted odds ratio (OR) =1.44, 95% confidence interval (CI), 1.05-1.98; P=0.026]. Further analysis of SVD subtypes revealed a moderate association with the ischaemic leukoaraiosis group [OR= 1.60, 95% CI, 1.14-2.25; P=0.007].

Conclusions:

Codon 10 of TGF-beta 1 might be a risk factor for SVD, specifically in ischaemic leukoaraiosis phenotype.
Elevated Free Fatty Acid is Associated with Cardioembolic Stroke Subtype
Authors: Seo Woo-Keun , Kim Juyeon , Kim Yoo Hwan , Kim Ji Hyun , Oh Kyungmi , Koh Seong-Beom , Seo Hong Seok
Published: December 2014

Background and Objectives:

Free fatty acids (FFAs), an important energy substrate, have an association with cardiovascular diseases, such as atherosclerosis, myocardial dysfunction and abnormal cardiac rhythm. However, limited reports are available on the association between FFAs and ischemic stroke. We hypothesized that plasma FFA concentration could be associated with an ischemic stroke, emphasizing the relationship between FFA and subtypes of ischemic stroke.

Methods:

A cross-sectional study examined the association between FFA concentration and subtypes of stroke and cerebral atherosclerosis from a hospital-based acute stroke registry.

Results:

Data of 715 stroke patients were analyzed. The concentration of FFA was highest in the cardioembolic stroke subtype compared with the other stroke subtypes. Logistic regression analysis revealed that an increase in FFA concentration was significantly associated with the cardioembolic subtype after the adjustment of covariates. FFA concentration was also higher in patients with atrial fibrillation (AF) than those without AF. According to the presence of atherosclerotic stenosis, no significantly difference of FFA concentration was found for intracranial and extracranial cerebral arterial atherosclerosis.

Conclusion:

Here we report a significant association between fasting FFA concentration and the cardioembolic stroke subtype. AF is suggested as the mediating factor between FFA and the cardioembolic stroke subtype.
A Canadian Paradox: Tommy Douglas and Eugenics
Authors: Shevell Michael
Published: December 2014

Tommy Douglas is an icon of Canadian 20th Century political history and is considered by many as the “Father” of Medicare, a key component of our national identity. Throughout his career, he was associated at both the provincial and federal levels with progressive causes concerning disadvantaged populations. In his sociology Master's thesis written in the early 1930's, Douglas endorsed eugenic oriented solutions such as segregation and sterilization to address what was perceived to be an endemic and biologically determined problem. At first glance, this endorsement of eugenics appears to be paradoxical, but careful analysis revealed that this paradox has multiple roots in religion, political belief, historical exposure and our own desire to view our collective history in a favourable light.
Biomarkers of Oxidative Stress in Vascular Dementia Patients
Authors: Shi Guang-Xia , Liu Cun-Zhi , Wang Lin-Peng , Guan Li-Ping , Li Si-Qian
Published: December 2014

Objective:

Little is known about the role of oxidative stress in the pathogenesis of vascular dementia (VaD). The aim of this study was to investigate the biomarkers of oxidative stress in urine, as reflected by 8-hydroxydeoxyguanosine (8-OHdG), 8-isoprostaglandin F2a (8-isoPGF2a) and nitrotyrosine (NT) levels, in a group of well characterized VaD patients and in two control groups of Vascular Not Demented (VaND) patients and healthy subjects.

Methods:

Ninety-six subjects from the Tianjin municipality in China were recruited. Forty-six patients were in the VaD group, 24 patients with VaND and 26 persons with no signs of cognitive disorder were employed as control groups. Urinary 8-OHdG and 8-isoPGF2a was performed using enzyme-linked immunosorbent assay (ELISA), and urinary NT levels were measured by chemiluminescence detection.

Results:

Significantly higher urinary 8-OHdG levels were detected in VaD patients compared to VaND patients and healthy control subjects. In contrast, urinary 8-isoPGF2a levels were significantly lower in VaD patients compared with two control groups. For NT levels, no statistically significant differences were observed among the three groups.

Conclusion:

Increased urinary 8-OHdG level was a potential marker of oxidative stress in VaD patients. Furthermore, it is also important to take into account potential confounders in order to improve the identification of changes in the status of oxidative stress as related to VaD.
Ethical Challenges with Awake Craniotomy for Tumor
Authors: Kirsch Brandon , Bernstein Mark
Published: December 2014

Background:

Awake brain surgery is useful for the treatment of a number of conditions such as epilepsy and brain tumor, as well as in functional neurosurgery. Several studies have been published regarding clinical results and outcomes of patients who have undergone awake craniotomy but few have dealt with related ethical issues.

Objective:

The authors undertake to explore broadly the ethical issues surrounding awake brain surgery for tumor resection to encourage further consideration and discussion.

Methods:

Based on a review of the literature related to awake craniotomy and in part from the personal experience of the senior author, we conducted an assessment of the ethical issues associated with awake brain tumor surgery.

Results:

The major ethical issues identified relate to: (1) lack of data; (2) utilization; (3) conflict of interest; (4) informed consent; (5) surgical innovation; and (6) surgical training.

Conclusion:

The authors respectfully suggest that the selection of patients for awake craniotomy needs to be monitored according to more consistent, objective standards in order to avoid conflicts of interest and potential harm to patients.
Improving the Neurological Exam Skills of Medical Students
Authors: Moore Fraser G. A. , Chalk Colin
Published: December 2014

Objective:

Determine if distributed practice of neurological exam (NE) skills in first year medical school produces sustained improvements in the skills of second year students.

Methods:

A prospective, controlled, non-blinded study conducted at McGill University (class size = 180 students). Expanded teaching of muscle stretch reflexes was provided to first year medical students. A structured examination of muscle stretch reflexes (max score = 100) was administered in second year medical school after a required two week rotation in Neurology. Results for class A (received the intervention in first year) were compared to the results for the preceding class B (had not received the intervention).

Results:

77 of 177 (44%) eligible students in class A and 69 of 166 (42%) eligible students in class B participated. Results were analyzed separately for each of two examiners. Mean (SD) scores were 95.2 (5.6) for class A (intervention) and 81.7 (11.1) for class B (control) for the first examiner and 90.4 (8.2) for class A and 83.8 (11.7) for class B for the second examiner. Results were statistically significant (Mann-Whitney test z = 5.27, p < 0.0001 first examiner and z = 2.67, p < 0.0038 second examiner).

Conclusions:

Distributed practice of muscle stretch reflexes during first year medical school results in improved performance by second year medical students after their mandatory clinical rotation in neurology, even when examined up to 14 months after the intervention. This finding has implications for the teaching of the NE.
Genetic Testing of Epileptic Encephalopathies of Infancy: An Approach
Authors: Sharma Suvasini , Prasad Asuri N.
Published: December 2014

The epileptic encephalopathies of infancy are a group of disorders characterized by intractable seizures, persistent abnormality of cortical function documented on EEG, and consequently impaired neuro-developmental outcomes. The etiologies vary and include; structural brain malformations, acquired brain insults, and inborn errors of metabolism in the majority of the affected patients. In a proportion of these cases no obvious etiology is identifiable on investigation. Recent advances in molecular diagnostics have led to the discovery of a number of gene defects that may be causal in many epileptic encephalopathies. Identification of the causative mutation is important for prognostic and genetic counseling, and may also carry treatment implications. The recently described genes include; Cyclin-Dependent Kinase-Like 5 gene (CDKL5), Protocadherin 19 (PCDH19), Sodium channel neuronal type 1a subunit gene (SCN1A), Aristaless-Related Homeobox Gene (ARX), and Syntaxin binding protein 1 gene (STXBP1), amongst others. Distinct electro-clinical syndromes are increasingly being identified amongst patients carrying the various mutations. In this review, we outline the approach to clinical evaluation and genetic testing of epileptic encephalopathies in infancy.
When Dementia is in the House: Needs Assessment Survey for Young Caregivers
Authors: Nichols Katherine R. , Fam David , Cook Cheryl , Pearce Michelle , Elliot Gail , Baago Sylvia , Rockwood Kenneth , Chow Tiffany W.
Published: December 2014

Objective:

To learn more about the needs and experiences of young carers for patients of frontotemporal dementia (FTD) in order to create a relevant support website for young caregivers to dementia patients.

Methods:

Two focus groups were held with a total of fourteen young carers aged 11-18. The data corpus was collected through a semi-structured interview facilitated by a medical journalist who had prior experience as a caregiver to a patient with FTD. The transcripts were narrowed to a dataset for descriptive analysis using a coding scheme to reveal the main themes of their responses.

Results:

Seven overlapping theme areas were: emotional impact of living with a parent with FTD, caregiving, coping, symptoms, diagnosis, relationships, and support. Based on the participants' responses, a website was launched providing supportive information and counsel for young carers.

Conclusion:

Young carers saw the experience of caring for a parent with early-onset dementia as positive overall, but identified opportunities for professionals to assist them in overcoming stigma and the challenge of balancing childhood and adolescent development within this context.
Establishing a Canadian Registry of Patients with Amyotrophic Lateral Sclerosis
Authors: Korngut L. , Genge A. , Johnston M. , Benstead T. , Bourque P. , Briemberg H. , Casey A. , D'Amour M. , Dupré N. , Figlewicz D. , Hader W. , Johnston W. , Kalra S. , Melanson M. , O'Connell C. , Rouleau G. , Shoesmith C. , Wee J. , Zinman L.
Published: December 2014

Background:

Amyotrophic lateral sclerosis (ALS) is a devastating cause of progressive weakness, respiratory failure and death. To date there is no effective therapy to meaningfully extend survival but continuously emerging targets and putative treatments are studied in clinical trials. Canadian epidemiological data on ALS is scarce and the socioeconomic impact of ALS on Canadian society is unclear. The Canadian Neuromuscular Disease Registry (CNDR) is a national clinic-based registry of patients with neuromuscular diseases with the goal of facilitating the design and execution of clinical research.

Methods:

We conducted a national stakeholder survey to assess interest for a Canadian ALS registry and an assessment of expected case ascertainment. A dataset derivation meeting was held to establish the registry medical dataset.

Results:

We report the results of the national stakeholder survey, case ascertainment assessment, and the derived dataset that have resulted in the current implementation of a Canadian registry of patients with ALS.

Conclusions:

The development of this long sought-after resource is a significant step forward for the Canadian ALS patient and research communities that will result in more efficient clinical trial recruitment and advancements in our understanding of ALS in Canada.
Prevalence of Lifestyle Risk Factors in Myotonic Dystrophy Type 1
Authors: Gagnon Cynthia , Chouinard Maud-Christine , Laberge Luc , Brisson Diane , Gaudet Daniel , Lavoie Mélissa , Leclerc Nadine , Mathieu Jean
Published: December 2014

Background:

The prevalence of unhealthy lifestyle habits such as smoking has seldom been described in neuromuscular disorders, including myotonic dystrophy type 1 (DM1). However, it is essential to document the unhealthy lifestyle habits as they can exacerbate existing impairments and disabilities. The objectives are: 1) To determine the prevalence of risk factors among individuals with DM1; 2) To compare the prevalence among classic and mild phenotypes.

Method:

A survey was done on a sample of two-hundred (200) patients with DM1 as part of a larger study. Lifestyle risk factors included being overweight or obese, tobacco smoking, illicit drug use, excessive alcohol consumption and physical inactivity. A registered nurse administered the validated public health survey. Categorization of risk factors were based on national standards and compared with provincial and regional prevalences.

Results:

50% of DM1 patients were overweight or obese, 23.6% were regular smokers, and 76% were physically inactive. Except for overweight and obesity, significant differences were observed between patients with classic and mild phenotypes for all the other lifestyle risk factors: those with the classic phenotype being more often regular smokers, consuming more often illicit drugs and being less physically active.

Conclusions:

The results of this study will provide guidance for the development of better adapted and focussed health promotion interventions in the future.
Diversity of ARSACS Mutations in French-Canadians
Authors: Thiffault I. , Dicaire M.J. , Tetreault M. , Huang K.N. , Demers-Lamarche J. , Bernard G. , Duquette A. , Larivière R. , Gehring K. , Montpetit A. , McPherson P.S. , Richter A. , Montermini L. , Mercier J. , Mitchell G.A. , Dupré N. , Prévost C. , Bouchard J.P. , Mathieu J. , Brais B.
Published: December 2014

Background:

The growing number of spastic ataxia of Charlevoix-Saguenay (SACS) gene mutations reported worldwide has broadened the clinical phenotype of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The identification of Quebec ARSACS cases without two knownSACSmutation led to the development of a multi-modal genomic strategy to uncover mutations in this large gene and explore phenotype variability.

Methods:

Search forSACSmutations by combining various methods on 20 cases with a classical French-Canadian ARSACS phenotype without two mutations and a group of 104 sporadic or recessive spastic ataxia cases of unknown cause. Western blot on lymphoblast protein from cases with different genotypes was probed to establish if they still expressed sacsin.

Results:

A total of 12 mutations, including 7 novels, were uncovered in Quebec ARSACS cases. The screening of 104 spastic ataxia cases of unknown cause for 98SACSmutations did not uncover carriers of two mutations. Compounds heterozygotes for one missenseSACSmutation were found to minimally express sacsin.

Conclusions:

The large number ofSACSmutations present even in Quebec suggests that the size of the gene alone may explain the great genotypic diversity. This study does not support an expanding ARSACS phenotype in the French-Canadian population. Most mutations lead to loss of function, though phenotypic variability in other populations may reflect partial loss of function with preservation of some sacsin expression. Our results also highlight the challenge ofSACSmutation screening and the necessity to develop new generation sequencing methods to ensure low cost complete gene sequencing.
Association of Serum Bilirubin with Stroke Severity and Clinical Outcomes
Authors: Xu Tian , Zhang Jintao , Xu Tan , Liu Wenqing , Kong Yan , Zhang Yonghong
Published: December 2014

Objective:

The aim of the study is to explore the association of serum bilirubin levels with admission severity and short term clinical outcomes among acute ischemic stroke patients.

Methods:

Data were collected from 2361 acute ischemic stroke patients in four hospitals of Shangdong Province during January 2006 and December 2008. National Institutes of Health Stroke Scale (NIHSS) was used to assess admission and discharge severity. NIHSS≥10 at discharge or in-hospital death was defined as short-term clinical outcomes. Logistic regression and trend test were used to examine the association of serum bilirubin levels with admission severity and short term clinical outcomes.

Results:

Serum bilirubin levels were significantly and positively associated with admission severity (P for trend <0.05). The age-sex adjusted odds ratios (95% confidential intervals) of NIHSS≥10 associated with the second, third and fourth quartile of total bilirubin/direct bilirubin were 1.245 (0.873, 1.777)/1.276 (0.895, 1.818), 1.484 (1.048, 2.102)/1.628 (1.158, 2.289) and 2.869 (2.076, 3.966)/2.765 (1.996, 3.828), respectively, compared with the lowest quartile; the multivariate adjusted odds ratios of NIHSS≥10 associated with the second, third and fourth quartile of total bilirubin/direct bilirubin were 1.088(0.711, 1.665)/1.436(0.94, 2.193), 1.328(0.877, 2.011)/1.647(1.092, 2.485) and 2.336(1.579, 3.458)/3.079 (2.049, 4.623), respectively, compared with the lowest quartile. However, no association between serum bilirubin levels and short-term clinical outcomes was observed in our study.

Conclusion:

Serum bilirubin levels were associated with initial stroke severity closely. Nevertheless, there is no significant relationship between serum bilirubin levels and short-term clinical outcomes among acute ischemic stroke patients.
Autoimmune Encephalopathies and Epilepsies in Children and Teenagers
Authors: Wong-Kisiel Lily C. , McKeon Andrew , Wirrell Elaine C.
Published: December 2014

Recognition of autoimmune encephalopathies and epilepsies in children and teenagers with acute or subacute onset of central nervous system dysfunction, through detection of the pertinent antibody on serum or cerebral spinal fluid, or through a response to immunotherapy may lead to an early diagnosis, and thus expedited implementation of immunotherapy and improved neurological outcome. The epidemiology of pediatric autoimmune encephalopathy and epilepsy is not well established, but advances in disease-specific biomarker discovery have lead to identification of disorders with either a cytotoxic T cell mediated pathogenesis or (more recently) possible autoantibody mediated disorders. This review summarizes the clinical presentations and recommended evaluations and treatment of pediatric epileptic encephalopathy suspected to be of autoimmune etiology.
Iron Deficiency Anemia Prevalence at First Stroke or Transient Ischemic Attack
Authors: Dubyk Melanie D. , Card Robert T. , Whiting Susan J. , Boyle Carol A. J. , Zlotkin Stanley H. , Paterson Phyllis G.
Published: December 2014

Background:

Iron deficiency anemia (IDA) has been implicated in the etiology of transient ischemic attack and ischemic stroke. This study aimed to: 1) document IDA prevalence in patients ≥ 65 years of age admitted to hospital with transient ischemic attack or first ischemic stroke, and 2) investigate dietary intake as a predictor of iron status.

Methods:

Ninety-four patients were enrolled. An algorithm containing values for hemoglobin, ferritin, total iron binding capacity, transferrin saturation, and serum transferrin receptor measured at admission was used to identify IDA. Usual dietary intake was assessed with the Clue II food frequency questionnaire.

Results:

Prevalence estimates were 6.4% for IDA, 2.1% for iron deficiency without anemia, and 6.4% for anemia from other causes. IDA prevalence was significantly higher than published National Health and Nutrition Examination Survey III (NHANES III) estimates for gender-specific age groups ≥ 70 years (One-Sample Proportion Test; males p = 0.038 [n= 37]; females p = 0.002 [n=44]). A comparison of IDA prevalence against selected controls from the NHANES III database yielded an odds ratio (OR) of 6.3, 95% confidence interval (CI) 0.8 to 53.7, which was not statistically significant (Fisher's Exact Test; n=94; p = 0.118). Multivariate linear regression analysis of dietary intake with indicators of iron status (n=58) revealed only iron supplements (p = 0.013) and heme iron intake (p = 0.038) as negative predictors of total iron binding capacity (p<0.05).

Conclusions:

These findings support the initiation of a prospective case control study to investigate IDA as a risk factor for ischemic stroke in elderly patients.
Treatment Comfort of Adult Neurologists in Childhood Onset Conditions
Authors: Oskoui M. , Wolfson C.
Published: December 2014

Background:

The majority of children with chronic neurodevelopmental disabilities are surviving to adulthood. Our goal was to assess how prepared and comfortable adult neurologists are in treating young adults with childhood onset chronic neurological conditions and evaluate the difficulty pediatric neurologists experience when transferring these patients to adult care.

Methods:

We conducted a cross-sectional study using two postal surveys of all pediatric and adult neurologists in the province of Quebec, Canada.

Results:

The response rate was 51.5%, with 119 neurologists completing the survey. Half of neurologists agreed that adult neurologists may not have adequate training in childhood onset disorders to prepare them to manage the disorders in adulthood, and 60% of pediatric neurologists reported having difficulty finding an adult provider for their patients. Adult neurologists were least comfortable treating patients with autism, chromosomal or metabolic disorders, and cognitive or behavioral disorders.

Conclusion:

Almost half of those surveyed believed that adult neurologists are not adequately trained to care for this growing patient population. Improving treatment comfort and knowledge among adult neurologists in childhood onset chronic neurological conditions may smooth the transition of these young adults from pediatric to adult care.
NASCET Percent Stenosis Semi-Automated Versus Manual Measurement on CTA
Authors: Lian Kevin , White Jeremy H. , Bartlett Eric S. , Bharatha Aditya , Aviv Richard I. , Fox Allan J. , Symons Sean P.
Published: December 2014

Purpose:

To compare North American Symptomatic Carotid Endarterectomy Trial (NASCET) stenosis values and NASCET grade categorization (mild, moderate, severe) of semi-automated vessel analysis software versus manual measurements on computed tomography angiography (CTA).

Methods:

There were four observers. Two independently analyzed 81 carotid artery CTAs using semi-automated vessel analysis software according to a blinded protocol. The software measured the narrowest stenosis in millimeters (mm), distal internal carotid artery (ICA) in mm, and calculated percent stenosis based on NASCET criteria. One of these two observers performed this task twice on each carotid, the second analysis was delayed two months in order to mitigate recall bias. Two other observers manually measured the narrowest stenosis in mm, distal ICA in mm, and calculated NASCET percent stenosis in a blinded fashion. The calculated NASCET stenoses were categorized into mild, moderate, or severe. Chi square and analysis of variance (ANOVA) were used to test for statistical differences.

Results:

ANOVA did not find a statistically significant difference in the mean percent stenosis when comparing the two manual measurements, the two semi-automated measurements, and the repeat semi-automated. Chi square demonstrated that the distribution of grades of stenosis were statistically different (p<0.05) between the manual and semiautomated grades. Semi-automated vessel analysis tended to underestimate the degree of stenosis compared to manual measurement.

Conclusion:

The mean percentage stenosis determined by semi-automated vessel analysis is not significantly different from manual measurement. However, when the data is categorized into mild, moderate and severe stenosis, there is a significant difference between semi-automated and manual measurements. The semi-automated software tends to underestimate the stenosis grade compared to manual measurement.
Pediatric Neurology Training in Canada: Current Status and Future Directions
Authors: Doja Asif
Published: December 2014

Background:

Child neurology training in Canada has changed considerably over time, with increasing requirements for standardized teaching of the fundamentals of child neurology and the CanMEDS competencies. We sought to determine the current status of child neurology training in Canada as well future directions for training.

Method:

A web-based survey was sent to program directors (PD's) of active pediatric neurology training programs. General questions about the programs were asked, as well as about success at the Royal College of Physicians and Surgeons of Canada (RCPSC) exam, breakdown of rotations, views on CanMEDS roles and questions on the future of pediatric neurology.

Results:

9/9 PD's completed the survey. 96.5% of all trainees successfully passed their RCPSC exam from 2001-2006. Breakdowns of the number and type of rotations for each year of training were provided. All CanMEDS roles were deemed to be important by PD's and programs have developed unique strategies to teach and assess these roles. 92.6% of trainees chose to go into academic practice, with the most popular subspecialty being epilepsy. All PD's favour joint training sessions particularly for neurogenetics and neuromuscular disease. Overall, PD's suggest recruitment for future child neurologists at the medical student level but are divided as to whether we are currently training too few or too many child neurologists.

Conclusions:

This survey provides a view of the current state of pediatric neurology training in Canada and suggestions for further development of postgraduate training. In particular, attention should be given to joint educational programs as well as urgently assessing the manpower needs of child neurologists.
Ketogenic Diet
Authors: Dhamija Radhika , Eckert Susan , Wirrell Elaine
Published: December 2014

About one third of patients with epilepsy are pharmacoresistent. For a subgroup of this population, the ketogenic diet can be highly efficacious and should be considered early. This review discusses the different types of ketogenic diet, proposed mechanism of actions and its evidence for use in children and adults with both generalized and focal epilepsies where surgery is not feasible. In addition we discuss a practical approach to diet initiation, maintenance and monitoring for side effects. We also summarize the emerging evidence for the use of ketogenic diet in a broad range of neurological disorders.
Traumatic Injury and Multiple Sclerosis: A Systematic Review and Meta-Analysis
Authors: Warren Sharon A. , Olivo Susan Armijo , Contreras Jorge Fuentes , Turpin Karen V. L. , Gross Douglas P. , Carroll Linda J. , Warren Kenneth G.
Published: December 2014

A systematic review/meta-analysis of literature addressing a possible association between traumatic injury and onset of multiple sclerosis was conducted. Medline, Embase, Cochrane DSR, Ovid HealthStar, CINAHL, ISI Web of Science and Scopus were searched for analytical studies from 1950 to 2011. Two investigators independently reviewed articles for inclusion, assessing their quality using the Newcastle-Ottawa Scale. Of the 13 case-control studies included, 8 were moderate quality and 5 low; of the 3 cohort studies 2 were high and 1 moderate. Meta-analysis including moderate and low quality case-control studies produced a modest but significant odds ratio: 1.41 (95% confidence interval: 1.03, 1.93). However, when low quality studies were excluded, the resulting odds ratio was non-significant. Cohort studies produced a non-significant standardized incidence ratio of 1.00 (95% confidence interval: 0.86, 1.16). These findings support the conclusion that there is no association between traumatic injury and multiple sclerosis onset; more high quality cohort studies would help to confirm this observation.