bluuebunny/crossref_metadata_2025 huggingface dataset:
A Follow-up Study of Infants with Intracranial Hemorrhage at Full-Term
Authors: Jhawar Balraj S. , Ranger Adrianna , Steven David A. , Maestro Rolando F. Del
Published: December 2014

Objective:

To determine physical and cognitive outcomes of full-term infants who suffered intracranial hemorrhage (ICH) at birth.

Methods:

A retrospective hospital-based, follow-up study of infants treated in London, Ontario between 1985 and 1996. Follow-up was conducted by telephone interviews and clinic visits. Outcome was measured according to physical and cognitive scales. Perinatal risk factors and hemorrhage characteristics were correlated with final outcome.

Results:

For this study 66 infants with ICH were identified, of which seven died during the first week of life. We obtained follow-up in all but ten cases (median = 3-years; range 1.0 to 10.9 years). Overall, 57% of infants had no physical or cognitive deficits at follow-up. Death occurred most frequently among those with primarily subarachnoid hemorrhage (19%) and the most favorable outcomes occurred among those with subdural hemorrhage (80% had no disability). In univariate models, thrombocytopenia (platelet count ≤ 70 x 109/L), increasing overall hemorrhage severity, frontal location and spontaneous vaginal delivery as opposed to forceps-assisted delivery increased risk for poor outcome. In multivariate models, all these factors tended towards increased risk, but only thrombocytopenia remained significant for physical disability (OR = 7.6; 95% CI = 1.02 – 56.6); thrombocytopenia was borderline significant in similar models for cognitive disability (OR = 4.6; 95% CI = 0.9 – 23.9).

Conclusion:

Although forceps-assisted delivery may contribute to ICH occurrence, our study found better outcomes among these infants than those who had ICH following a spontaneous vaginal delivery. Hemorrhage in the frontal lobe was the most disabling hemorrhage location and if multiple compartments were involved, disability was also more likely to occur. However, in this report we found that the factor that was most likely to contribute to poor outcome was thrombocytopenia and this remained important in multivariate analysis.
Concurrence of glioma and multiple sclerosis
Authors: Khan Shah-Naz Hayat , Buwembo Joseph E. , Li Q.
Published: December 2014

A 29-year-old Caucasian female diagnosed with multiple sclerosis (MS) for seven years, presented with a history of headaches and a single episode of new onset seizures. Her physical examination was unremarkable and she was placed on anti-seizure medications. A computed tomography (CT) scan showed a right frontal brain lesion causing minimal mass effect (Figure 1). Magnetic resonance imaging (MRI) revealed a large nonenhancing space occupying lesion in the right frontal lobe, in addition to numerous smaller lesions which were characteristic of MS plaques (Figures 2 & 3). The large lesion was causing mass effect with right to left midline shift (Figures 2, 3A & B). Given the patient’s history, the appearance and unusually large size of the frontal lesion, it was unclear whether it was a demyelinating MS plaque, or an intra-axial tumour.
Transient Edematous Lesions of the Splenium in Epileptic Patients
Authors: Carrara Giovanna , Ferlazzo Edoardo , Tampieri Donatella , Andermann Frederick , Melanson Denis
Published: December 2014

Background:

Transient focal lesions in the splenium of the corpus callosum (SCC) have been previously described in patients with epilepsy or without epilepsy but receiving antiepileptic drugs (AED).

Case reports:

Two epileptic patients were admitted to our long-term monitoring unit. Antiepileptic drugs were completely discontinued a few days later. One patient had no seizures. The other had three attacks, the last of which occurred two days before a brain magnetic resonance imaging (MRI) was performed. In both cases brain MRI showed a lesion in the SCC characterized by high signal on T2-weighted images and no enhancement after Gadolinium infusion. The patients were discharged with their pre-admission medications. A follow-up MRI five weeks later showed resolution of the SCC lesions.

Conclusions:

The pathogenesis of transient SCC lesions in epileptic patients is still unclear. In our patients, either the sudden AED withdrawal or the seizures activity may be presumed to be the cause, though an individual susceptibility must also be considered.
Sudden Quadriplegia after Acute Cervical Disc Herniation
Authors: Sadanand Venkatraman , Kelly Michael , Varughese George , Fourney Daryl R.
Published: December 2014

Background:

Acute neurological deterioration secondary to cervical disc herniation not related to external trauma is very rare, with only six published reports to date. In most cases, acute symptoms were due to progression of disc herniation in the presence of pre-existing spinal canal stenosis.

Case report:

A 42-year-old man developed weakness and numbness in his arms and legs immediately following a sneeze. On physical examination he had upper motor neuron signs that progressed over a few hours to a complete C5 quadriplegia. An emergent magnetic resonance imaging study revealed a massive C4/5 disc herniation. He underwent emergency anterior cervical discectomy and fusion. Postoperatively, the patient remained quadriplegic. Eighteen days later, while receiving rehabilitation therapy, he expired secondary to a pulmonary embolus. Autopsy confirmed complete surgical decompression of the spinal cord.

Conclusions:

Our case demonstrates that acute quadriplegia secondary to cervical disc herniation may occur without a history of myelopathy or spinal canal stenosis after an event as benign as a sneeze.
Hypertension and Stroke: 2005 Canadian Hypertension Educational Program Recommendations
Authors: Boulanger J.M. , Hill Michael D. ,   on behalf of the CHEP (Canadian Hypertension Educational Program)
Published: December 2014

Background:

Hypertension is the most important modifiable cause of stroke. The Canadian Hypertension Educational Program, representing Canada's experts in the field of hypertension, publishes annual evidence-based recommendations on the diagnosis and treatment of hypertension.

Methods:

We present the 2005 Canadian Hypertension Educational Program guidelines regarding the management of hypertension in patients with stroke.

Results:

The diagnosis of hypertension should be expedited and can be made as early as the second visit in patients with stroke. Unless contraindicated, a combination of angiotensin-converting-enzyme (ACE) inhibitors and diuretics is the preferred therapy in these patients. A target blood pressure below 140/90mmHg for non-diabetic patients, below 130mmHg/80mmHg for diabetic patients and below 125mmHg/75mmHg for those with renal disease and proteinuria (³ 1 gram per day) should be reached. Lifestyle interventions may be as effective as medication and should be used in conjunction with medical management. Waist circumference should be less than 102cm for men and 88cm for women. There remains uncertainty about the management of high blood pressure in the context of acute stroke.

Conclusions:

A combination of ACE-inhibitors and diuretics is recommended in hypertensive stroke patients. Blood pressure should be maintained below 140/90 mmHg.
Highlights of the 2002 Canadian Neurological Society (CNS) Manpower Survey
Authors: Bailey Peter , Warren Sharon , Buske Lynda
Published: December 2014

Background:

The Canadian Neurological Society commissioned a manpower survey in 2002 to assess demographics, distribution, specialty interests, working conditions, job satisfaction and future plans of neurologists across the country.

Methods:

A survey was mailed to all known Canadian neurologists (n = 694) on two separate occasions. Further encouragement by telephone contact was undertaken. The response rate was 54%.

Results:

The mean age of neurologists who responded was 51 years, with 14% being women. Approximately 55% of neurologists were community-based. Seventy-six percent designated a sub-specialty interest. On average, neurologists worked 57 hours per week and the majority had significant “on-call” commitments. Job satisfaction was higher among academic neurologists when compared with community-based neurologists, and greater among men than women. A greater percentage of older neurologists were satisfied with their work than their younger colleagues. Significant attrition in the neurological work force is a major concern, since up to 20% of neurologists reported that they are likely to retire in the next five years and about 15% are likely to reduce their practice.

Conclusions:

This survey suggests that substantial concerns are facing Canadian neurology over the next five years. Major efforts to retain existing expertise and enhance residency training will be required to simply maintain the present quality of neurological care in Canada.
The Numbers Needed to Treat for Neurological Disorders
Authors: Bussière Miguel , Wiebe Samuel
Published: December 2014

Background:

Numerous therapeutic interventions have been developed in the neurosciences. Clinicians need summary measures about efficacy of therapies that derive from the best available evidence, and that can be readily extrapolated to clinical practice. The number needed to treat (NNT) is intuitive and clinically applicable. We provide clinicians with a single source that summarizes important therapies in the main neurological and neurosurgical areas.

Methods:

Critically appraised evidence about therapies in the neurosciences was obtained from meta-analyses in all neurosciences groups in the Cochrane library, and from critically appraised topics at the University of Western Ontario. Therapies were included if they were deemed relevant and if outcomes were dichotomous. For each therapy, we obtained absolute risk differences and their 95% confidence intervals (CI), the corresponding NNTs, control and experimental event rates, and the time-frame of the outcome assessment.

Results:

We assembled a table of NNTs for 87 interventions in ten disease categories, deriving from meta-analyses (70%) or randomized controlled trials (30%), and assessing surgical interventions (7%), procedures (9%) or pharmacological treatments (84%). The NNTs varied widely, ranging from 1 in the use of epidural blood patch for post-dural puncture headache to 4608 for meningococcal vaccination. Preventative interventions had substantially larger NNTs. Time-frames were inappropriately short for many chronic conditions.

Conclusions:

Large collections of NNTs provide useful, updateable summaries of therapeutic effects in the neurosciences, an increasingly interventional clinical field.
The Reliability of Ultrasound Measurements of Carotid Stenosis Compared to MRA and DSA
Authors: Honish Colin , Sadanand Venkatraman , Fladeland Derek , Chow Vance , Pirouzmand Fahrad
Published: December 2014

Objective:

Carotid ultrasound (US) is a screening test for patients with transient ischemic attacks (TIAs) or stroke who then undergo Digital Subtraction Angiogram (DSA) or Magnetic Resonance Angiography (MRA). Gold standard DSA is invasive with inherent risks and costs. MRA is an evolving technology. This study compares reliability of MRA and US modes with DSA in determining degree of internal carotid artery stenosis.

Methods:

A five year retrospective analysis of 140 carotid arteries from patients who had carotid US and DSA, and possibly Magnetic Resonance Angiography was undertaken. Recorded US parameters were peak systolic velocity (PSV), end diastolic velocity (EDV), and ICA/CCA peak systolic velocity ratio. The MRA and DSA parameters used NASCET technique for measuring stenosis. Statistical analysis included ROC curves and Kappa computation.

Results:

US grading of carotid stenosis can be made more reliable by choosing appropriate parameters. The best combination of sensitivity and specificity for stenosis > 70% in our hospital was seen at PSV > 173cm/s (sensitivity 0.87, specificity 0.8, Positive Predictive Value (PPV) 0.70, Negative Predictive Value (NPV) 0.93, kappa 0.64 and weighted kappa 0.71). MRA kappa was 0.78, (sensitivity 0.75, specificity 1.0, PPV 1.0, NPV 0.85).

Conclusions:

US parameters should be validated in each centre. At best, US can only approximate the accuracy of DSA, probably due to inherent limitations of this modality. Magnetic Resonance Angiography has a perfect specificity and PPV but this technique needs to be standardized. Simultaneous use of MRA and US for screening increases sensitivity to over 0.9 without compromising specificity in > 70% stenosis.
How Well Does Neurology Residency Mirror Practice?
Authors: Moore Fraser G.A. , Chalk Colin
Published: December 2014

Objective:

To report the residency training experience of two neurologists, focusing on setting and diagnoses encountered.

Methods:

Data from prospective patient logs kept by the authors during residencies completed a decade apart were compared with each other and the literature.

Results:

The range of diagnoses was broadly similar between residencies, as were the proportions of common or uncommon disorders, and the proportion of cases without a neurological diagnosis. Although most patients were seen in in-patient settings, the rates at which common neurological conditions and functional disorders were seen was comparable to published experiences of community neurologists.

Conclusions:

The diagnostic profile of North American neurology residency appears to be relatively stable, regardless of location or date of training. In several respects, the content of current neurology residencies mirrors clinical practice well. Changes to residency training are doubtless needed, but they should be guided by a clear understanding of the experiences of contemporary trainees.
Management of Chronic Subdural Hematoma: A National Survey and Literature Review
Authors: Cenic Aleksa , Bhandari Mohit , Reddy Kesava
Published: December 2014

Objective:

To survey neurosurgical practices in the treatment of chronic and subacute subdural hematoma in the Canadian adult population.

Methods:

We developed and administered a questionnaire to Canadian Neurosurgeons with questions relating to the management of chronic and subacute subdural hematoma. Our sampling frame included all neurosurgery members of the Canadian Neurosurgical Society.

Results:

Of 158 questionnaires, 120 were returned (response rate = 76%). The respondents were neurosurgeons with primarily adult clinical practices (108/120). Surgeons preferred one and two burr-hole craniostomy to craniotomy or twist-drill craniostomy as the procedure of choice for initial treatment of subdural hematoma (35.5% vs 49.5% vs 4.7% vs 9.3%, respectively). Craniotomy and two burr-holes were preferred for recurrent subdural hematomas (43.3% and 35.1%, respectively). Surgeons preferred irrigation of the subdural cavity (79.6%), use of a subdural drain (80.6%), and no use of anti-convulsants or corticosteroids (82.1% and 86.6%, respectively). We identified a lack of consensus with keeping patients supine following surgery and post-operative antibiotic use.

Conclusion:

Our survey has identified variations in practice patterns among Canadian Neurosurgeons with respect to treatment of subacute or chronic subdural hematoma (SDH). Our findings support the need for further prospective studies and clinical trials to resolve areas of discrepancies in clinical management and hence, standardize treatment regimens.
A Rehabilitation Program for Patients Recovering from Severe Stroke
Authors: Teasell Robert W. , Foley Norine C. , Bhogal Sanjit K. , Chakravertty Raja , Bluvol Anna
Published: December 2014

Objective:

The purpose of this study was to describe the outcomes of patients with a severe stroke admitted to a specialized “slow stream” rehabilitation program and to develop a model to predict discharge destination.

Methods:

Chart review of 196 consecutive non-ambulatory (“lower-band”) stroke patients admitted between 1996-2001, to a specialized in-patient rehabilitation unit designed to accommodate the needs of patients with profound disabilities, and who were considered inappropriate for conventional inpatient rehabilitation programs. Special features of this program included the availability of an independent living unit, therapies tailored to individual tolerance and the opportunity to remain on the unit for an extended period until such time that the patients' rehabilitation potential had been maximized.

Results:

Patients were admitted to the unit after a median of 49 days following stroke onset. Their median admission and discharge functional independence measure (FIMTM) scores were 46 and 70, respectively. The improvement in ability to perform self-care tasks was statistically significant (Z= -11.18, p<0.0001). By discharge, 54 patients (28%) were able to ambulate independently (with or without an assistive device), while 142 patients (72%) remained wheelchair dependent. Eighty-five patients (43%) returned to their own home upon rehabilitation discharge, while the remainder were admitted to nursing homes or hospitals closer to the patients' home. Admission FIM score, age, no previous history of stroke and male sex were the variables found to most strongly predict discharge home.

Conclusions:

Patients with severe strokes who received individualized care on a highly specialized stroke rehabilitation unit achieved impressive functional outcomes despite a lag of seven weeks post stroke before rehabilitation was initiated. Many patients were no longer wheelchair dependent and almost half returned home. Active rehabilitation should not be limited to “middle-band” stroke patients.
Use of Complementary and Alternative Medical Therapies in a Pediatric Neurology Clinic
Authors: Soo Isaac , Mah Jean K. , Barlow Karen , Hamiwka Lorie , Wirrell Elaine
Published: December 2014

Background:

Complementary and alternative medicine (CAM) is increasingly used in adults and children. Studies on CAM in neurological disorders have focused on the adult population and its use among pediatric neurology patients has not been well characterized.

Objectives:

The purpose of this study was: 1) To characterize the prevalence of CAM in pediatric neurology patients; 2) To determine the perceived effectiveness of CAM in these children; 3) To compare the cost of CAM with conventional therapies; and 4) To describe caregiver or patient-related variables associated with the use of CAM.

Methods:

This was a cross-sectional survey of patients and families attending the Alberta Children's Hospital neurology clinic between February and May 2004. Patients were considered eligible if they were between two and 18 years of age and had a known history of neurological disorders. Caregivers completed several self-administered questionnaires regarding their socio-demographic profile, their child's neurological illness, and their experience with CAM. Caregivers also rated their child's quality of life using the Pediatric Quality of Life Inventory.

Results:

One hundred and five of 228 (46%) families completed the survey. The mean age of the neurology patients was 9.8 ± 4.5 years. Forty-six (44%) out of 105 patients received one or more types of CAM, with the most common types being chiropractic manipulations (15%), dietary therapy (12%), herbal remedies (8%), homeopathy (8%), and prayer/faith healing (8%). Caregivers' sociodemographic variables or pediatric health-related quality of life were not significantly associated with the use of CAM. Fifty-nine percent of CAM users reported benefits, and only one patient experienced side effects. There was no significant difference in the total median cost of CAM compared to conventional therapies ($31.70 vs. $50.00 per month). Caregivers' personal experience or success stories from friends and media were common reasons for trying CAM.

Conclusions:

The use of CAM was common among pediatric neurology patients. Over half of the families reported benefits with CAM, and side effects were perceived to be few. Physicians should initiate discussion on CAM during clinic visits so that the families and patients can make informed decisions about using CAM. Further studies should address the specific role of CAM in children with neurological disorders, and to determine the potential interactions between CAM and conventional therapies in these patients.
Canadian Association of Neurosciences Review: Postnatal Development of the Mammalian Neocortex: Role of Activity Revisited
Authors: Zhang Zhong-wei
Published: December 2014

The mammalian neocortex is the largest structure in the brain, and plays a key role in brain function. A critical period for the development of the neocortex is the early postnatal life, when the majority of synapses are formed and when much of synaptic remodeling takes place. Early studies suggest that initial synaptic connections lack precision, and this rudimentary wiring pattern is refined by experience-related activity through selective elimination and consolidation. This view has been challenged by recent studies revealing the presence of a relatively precise pattern of connections before the onset of sensory experience. The recent data support a model in which specificity of neuronal connections is largely determined by genetic factors. Spontaneous activity is required for the formation of neural circuits, but whether it plays an instructive role is still controversial. Neurotransmitters including acetylcholine, serotonin, and γ-Aminobutyric acid (GABA) may have key roles in the regulation of spontaneous activity, and in the maturation of synapses in the developing brain.
ASPECT Scoring to Estimate >1/3 Middle Cerebral Artery Territory Infarction
Authors: Demaerschalk Bart M. , Silver Brian , Wong Edward , Merino Jose G. , Tamayo Arturo , Hachinski Vladimir
Published: December 2014

Purpose:

To compare the inter-observer reliability of Alberta Stroke Programme Early CT Scoring (ASPECTS) with the ICE (Idealize-Close-Estimate) method of estimating > 1/3 middle cerebral artery territory (MCAT) infarction amongst stroke neurologists and to determine how well ASPECT Scoring predicts > 1/3 MCAT infarctions in acute ischemic stroke (AIS).

Background:

The European Cooperative Acute Stroke Study suggested that > 1/3 involvement of the MCAT on early CT scan was a risk factor for symptomatic intracerebral hemorrhage (SICH) following treatment with tissue plasminogen activator (tPA) for AIS but, in the absence of a systematic method of estimation had poor interobserver reliability (Kappa 0.49). The ICE method was developed to standardize the approach to estimating early MCAT infarct size and has very good interobserver reliability (Kappa 0.72). ASPECTS has comparable interobserver reliability and is reported to predict both neurological outcome and SICH.

Methods:

Five stroke neurologists were tested with 40 AIS CT scans. Each performed blinded independent assessments of early ischemic changes with both ASPECTS and ICE. The reference standard was majority opinion of 1/3 MCAT determination of five neuroradiologists. A receiver operator curve (ROC) was constructed and likelihood ratios (LR) were calculated. Chance corrected agreement (kappa) and chance independent agreement (phi) were calculated for both methods, and analysis of variance was used to calculate reliability by intraclass correlation coefficient (ICC) for ASPECTS.

Results:

The LR for a positive test (> 1/3 MCAT) were extremely large and conclusive (approaching infinity) for ASPECTS of 0-3; were large and conclusive (30, 20, and 10) for ASPECTS of 4, 5, and 6 respectively; was an unhelpful 1 for ASPECTS of 7, and were again extremely large and conclusive (approaching zero) for ASPECTS of 8-10. A ROC plot supported an ASPECTS cutoff of < 7 as best for 1/3 MCAT estimation (94% sensitivity and 98% specificity). Kappa and Phi statistics were moderately good for both ASPECTS and ICE (0.7). ICC for ASPECTS was 0.8.

Conclusion:

When experienced stroke neurologists utilize a formalized method of quantifying early ischemic changes on CT, either ASPECTS or ICE, the interobserver agreement and reliability are satisfactory. ASPECTS allows for a strong and conclusive estimation of the presence of 1/3 MCAT involvement and a cutoff point of < 7 results in best test performance.
Morbidity Associated With the Use of Intracranial Electrodes for Epilepsy Surgery
Authors: Burneo Jorge G. , Steven David A. , McLachlan Richard S. , Parrent Andrew G.
Published: December 2014

Background:

Invasive monitoring for the investigation of medically intractable epilepsy may be associated with undesirable morbidity. We performed a review of our recent experience to determine the incidence of major complications.

Methods:

We reviewed the clinical records of all patients who underwent invasive EEG monitoring at our institution between 2000 and 2004.

Results:

One-hundred and sixteen patients (57 males, 59 females) with a mean age of 32 years of age underwent intracranial placement of electrodes for epilepsy surgery investigation. Subdural strips were placed in 115 patients with a mean of eight strips per patient. Subdural grids were inserted in 11 patients and depth electrodes in five. Fourteen of the 15 patients with grids or depth electrodes also had strips. Coverage was unilateral in 37 patients and bilateral in 79 patients. Electrodes were placed over the frontal lobe in 78 cases, temporal in 93, parietal in 24, and occipital in 27 patients. The average duration of investigation was 12.3 days (range 3-29). The evaluation led to the performance of a surgical resection in 85 patients (74%). Complications were seen in four patients with subdural strips (3%), and in two patients with grids (13%), characterized by clinical infection, intracranial hemorrhage, aseptic meningitis, transient neurological deficits, and status epilepticus. Mortality was nil.

Conclusion:

In comparison with previously published literature on the topic, the major complication rate in this group of patients appears to be low.
A Pediatric Case of Reversible Segmental Cerebral Vasoconstriction
Authors: Kirton Adam , Diggle John , Hu William , Wirrell Elaine
Published: December 2014

Background:

Reversible segmental cerebral vasoconstriction (RSCV) is a recognizable clinical and radiographic syndrome consisting of thunderclap headache with or without focal neurological symptoms combined with reversible segmental vasoconstriction of proximal cerebral blood vessels.

Methods:

We report a case of reversible segmental cerebral vasoconstriction in a child.

Results:

A healthy 13-year-old boy experienced the sudden onset of a severe, diffuse headache upon surfacing from a deep dive in a swimming pool. Severity was maximal at the onset and improved over several hours. The same headache recurred three times over the next four days and a low baseline headache persisted throughout. Vomiting occurred once and mild photo/osmophobia were reported but throbbing, aura, or autonomic symptoms were absent. Focal neurological signs or symptoms were absent and he denied previous history of headaches, medications, drugs, or trauma. Two normal CT scans were performed within hours of separate headaches. Cerebrospinal fluid study on day 5 was bloody with no xanthochromia. MRI/MRA/MRV of the brain and vasculitic work-up were normal. Cerebral angiography on day 6 demonstrated smooth narrowing of multiple proximal cerebral vessels including supraclinoid internal carotid artery (ICA), M1, and A1 on the right and M1 on the left. By ten days, the patient's headaches had resolved and repeat angiography was normal.

Conclusion:

RSCV should be considered in a child with thunderclap headache.
Immunizations and Autism: A Review of the Literature
Authors: Doja Asif , Roberts Wendy
Published: December 2014

Because of a temporal correlation between the first notable signs and symptoms of autism and the routine childhood vaccination schedule, many parents have become increasingly concerned regarding the possible etiologic role vaccines may play in the development of autism. In particular, some have suggested an association between the Measles-Mumps-Rubella vaccine and autism. Our literature review found very few studies supporting this theory, with the overwhelming majority showing no causal association between the Measles-Mumps-Rubella vaccine and autism. The vaccine preservative thimerosal has alternatively been hypothesized to have a possible causal role in autism. Again, no convincing evidence was found to support this claim, nor for the use of chelation therapy in autism. With decreasing uptake of immunizations in children and the inevitable occurrence of measles outbreaks, it is important that clinicians be aware of the literature concerning vaccinations and autism so that they may have informed discussions with parents and caregivers.
Randomized Trials and Collaborative Research in Epilepsy Surgery: Future Directions
Authors: Wiebe Samuel , Jette Nathalie
Published: December 2014

Background:

Although randomized controlled trials (RCTs) are the gold standard for evaluating therapeutic interventions, surgical RCTs are particularly challenging and few have been done in the field of epilepsy surgery. We assess the level of RCT activity in epilepsy surgery and propose feasible alternatives to develop sustainable research initiatives in this area.

Methods:

We undertook a systematic review of the world literature to assess the level of RCT activity in epilepsy surgery. Previous personal experience with RCTs in epilepsy surgery and examples of successful Canadian multicentre research networks were reviewed to propose initiatives for sustainable, valid research in epilepsy surgery.

Results:

We identified 12 RCTs in epilepsy surgery, including 692 patients, of whom 416 were involved in vagus nerve stimulation, 16 in various brain electrostimulation procedures, 180 in comparisons of different surgical techniques, and 80 in a comparison of medical versus surgical therapy. Most studies were of short duration (median = 3 months, range 3-12 months). In the area of resective surgery, only temporal lobe epilepsy has been subjected to any type of RCT comparison. All RCTs have been done within the last 13 years. There were no multicentre Canadian surgical studies.

Conclusion:

The adoption of RCTs in epilepsy surgery has been slow and difficult worldwide. Because of its universal health care system and its well established epilepsy surgery centres, Canada is in a strong position to create a national epilepsy surgery research initiative capable of undertaking high quality, sustainable research in epilepsy surgery.
A 10-Year-Old Girl with Progressive Generalized Weakness
Authors: Mah Jean K. , Sarnat Harvey B.
Published: December 2014

Case Presentation

Dr. Harvey Sarnat:A.Y. was a 10-year-old Mexican girl who presented with a 7-year history of progressive weakness. She was the full-term product of an uncomplicated pregnancy and delivery, weighing 2850 grams at birth. Early developmental milestones were achieved at the expected rate until age three, when frequent falling was noted. Progressive weakness of her legs ensued, and at age nine years, A.Y. lost the ability to walk beyond a few steps, and shortly thereafter she could not stand without support. She had no seizures, visual disturbance, dysphagia, or incontinence. Previously an excellent student, her academic performance in school had deteriorated over the past year. She was not on any medications. Family history was negative for any known neurological or neuromuscular diseases. A.Y. was an only child. Both parents were alive and well; there was no history of consanguinity.
N. Paucivorans Infection Presenting as a Brain Abscess
Authors: Khan Shah-Naz Hayat , Sanche Stephen E. , Robinson Christopher A. , Pirouzmand Farhad
Published: December 2014

We report an intracerebral abscess caused by a recently identified nocardial species, in an immunocompetent individual without extraneural involvement.

A 63-year-old non-smoking Caucasian male with an unremarkable history of hypertension, presented with a 2-week history of personality changes including apathy, some difficulty walking, a tendency to veer to the left and a possible seizure. Preliminary assessment, including laboratory investigations were unremarkable. Computed tomography (CT) of his brain revealed a right frontal lobe multi-loculated, ring-enhancing lesion with vasogenic edema and associated mass effect (Figure 1). He was then referred to our institution.
Consent in Alzheimer's Disease Research: Risk/Benefit Factors
Authors: Beattie B. Lynn
Published: December 2014

In the era of chronic disease, we are challenged to find therapies that provide symptomatic relief and ideally, alter the course of the underlying disease. In Alzheimer's disease (AD), these issues are complicated by the disease itself, which affects the subject's decision-making capacity for participation in the research. According to established ethical guidelines it is clear that individuals with impaired capacity may participate in research and their risk should be no greater than that which the individual would have in day to day activities with anticipation of benefits within that realm. Decision making processes are complex and involve proxies who themselves have biases about their loved one and the potential for participating in the research. Newer disease-modifying approaches such as immunotherapy have potential for affecting the course of the underlying disease but with greater risk of more significant side effects. Ideally the health care of the subjects is not disadvantaged by research participation. At the same time, trials of potentially riskier therapy are relevant in subjects with the disease. Research for subjects with AD must have appropriate safeguards in place to enable effective progress in innovative therapy for a vulnerable, often elderly population. Recommendations are made which could further our capacity to undertake ethical research in the AD population.
Alternatives to Placebo-Controlled Trials
Authors: Streiner David L.
Published: December 2014

Until recently, the gold standard for assessing the efficacy and effectiveness of new medications has been the placebocontrol randomized clinical trial (RCT). However, there are serious ethical concerns about placing patients on a placebo when effective treatments exist. Further, if a new agent is tested only against a placebo, there is no guarantee that it is more effective, or even as effective, as an existing agent. For these and other reasons, ethicists and regulatory bodies have said that, under these circumstances, new drugs should be tested against an active agent. There are three types of such trials: superiority, equivalence, and non-inferiority. In superiority trials, the goal is to establish that the new drug is better (i.e., more effective, or with a more benign side-effect profile) than the standard. Because such trials require much larger sample sizes than placebo-control studies, and are rarely required to bring a drug onto market, they are rarely done. In equivalence trials, the aim is to show that the new and standard agents have similar degrees of effectiveness or adverse events. Due to sample size requirements, most studies of new drugs are non-inferiority trials, in which it is sufficient to demonstrate that the new drug is not significantly worse than the existing ones. However, there are methodological concerns with equivalence and non-inferiority trials, including (a) an inability to determine if the drugs were equally good or equally bad; (b) poorly executed trials with low power can be mistaken for “proving” equivalence or non-inferiority; (c) the equivalence interval is arbitrary; (d) successive non-inferiority trials may lead to a gradual reduction in effectiveness; and (e) often larger trials are necessary. The paper also discusses “add on trials.” It is recommended that, even when existing drugs exist, trials should consist of at least three arms, one of which is a placebo. This paper briefly considers the ethics of placebo, and conditions are stated under which such studies can be conducted.
Global Assessment Measures for Assessing Efficacy in Dementia Drug Trials
Authors: Rockwood Kenneth
Published: December 2014

The use of judgment-based global measures of clinical treatment effects has a long history in the regulatory approval of drugs for the treatment of dementia. This paper reviews current use of these measures, noting several practical difficulties with their implementation. Importantly, global measures have usually yielded general estimates of drug effects similar to psychometric test batteries, even though correlations between global and psychometric measures at the individual patient level is modest. Like psychometric tests, global measures can tell us that some clinically detectable effect is present but often yield only limited evidence about what those effects might be. Steps should be taken to improve the specificity of treatment effect description and to incorporate patient/caregiver preferences in global measures about disease treatment in dementia.
Is Mild Cognitive Impairment a Valid Target of Therapy
Authors: Rockwood Kenneth , Chertkow Howard , Feldman Howard H.
Published: December 2014

The status of Mild Cognitive Impairment (MCI) as a valid construct is controversial. The term encompasses people with heterogeneous clinical profiles, and invites sub-classifications that still require validation. Still, much evidence suggests that, properly selected, many people with MCI - especially Amnestic MCI - are at a high risk of dementia. This paper considers the validity of the construct of MCI as a high-risk state for progression and a target for treatment. We conclude that the status of MCI as an entity remains controversial. On the one hand, it can be argued that the careful section of cases at high risk of developing dementia means that it is a valid target, with the goal being the prevention of dementia. Advocates of this view see a linear progression that they are trying to arrest, but studies have yet to show that this can be done. On the other hand, it can be argued that the patients who progressed did not develop dementia: they actually had a very early form of it. By this view, people without the progressive form will be needlessly exposed to antidementia drugs, and the others should be treated anyway. Why some people progress and others do not is not clear, but the variable rates of progression - between clinic-based and population-based samples and between very similar clinical trials with slightly different inclusion criteria - suggests that MCI is a heterogeneous entity. The phenomenon of slowing or non-progression itself should be investigated, and such investigations likely should extend to people now classified as having mild dementia.
Improving Drug Trials for Mild to Moderate Alzheimer's Disease
Authors: Hogan David B.
Published: December 2014

Over the last two decades, numerous studies have been conducted on subjects with mild to moderate Alzheimer's disease. The objective of this paper was to review concerns raised in the literature about the design and methodology of these clinical trials and to make recommendations to deal with the limitations identified. Concerns raised in the literature include the following: undue focus on statistical rather than clinical significance; the need for further pharmacoeconomic evaluations; the nonrepresentativeness of the study populations; perceived inadequacies in the direct-comparison studies conducted to date; the limitations of open-label extension studies; the inability of standard psychometric tools to document all the relevant treatment effects; the ethics of placebo-controlled trials; and, problems caused by the actions of the regulatory authorities. Recommendations are made to deal with the issues raised.
Perivascular Spaces: Normal and Giant
Authors: Fanous Randy , Midia Mehran
Published: December 2014

The purpose of this paper is to discuss both normal perivascular spaces (PVSs) and pathological giant perivascular spaces (GPVSs). The anatomy and physiology of normal PVSs, including important immunological and lymphatic roles, are described. Special attention is given to the Magnetic Resonance Imaging (MRI) findings of both normal and GPVSs. Furthermore, the clinical features and pathogenesis of GPVSs are explored, with special emphasis on the pathological implications of these lesions, and their relevance. It is important that symptomatic GPVSs not be mistaken for more devastating disease processes. When the lesions in question occur in a characteristic location along the path of a penetrating vessel, are isointense with cerebrospinal fluid on all MRI sequences, do not enhance with contrast material, are not calcified, and have normal adjacent brain parenchyma, their appearance is pathognomonic of GPVSs. The clinician should realize that an extensive differential diagnosis is superfluous and that biopsy is unnecessary in these patients. Instead, the clinical focus should be aimed at neurosurgical intervention, as dictated by the symptoms of mass effect.
ALS Incidence in Nova Scotia Over a 20- Year-Period: A Prospective Study
Authors: Bonaparte J.P. , Grant I.A. , Benstead T.J. , Murray T.J. , Smith M.
Published: December 2014

Objective:

Previous studies have suggested that the incidence of amyotrophic lateral sclerosis (ALS) in Nova Scotia is relatively high and increasing over time. This study was performed to determine the current incidence of ALS in Nova Scotia and to compare this to data collected in 1984 and 1995.

Methods:

All physiatrists and neurologists were surveyed on a monthly basis over one year to record all new cases of ALS diagnosed in Nova Scotia. Data was compared to that collected using similar methods in 1984 and 1995. To validate our methods, we also performed a retrospective study using a provincial health care database.

Results:

There were 21 new ALS cases in Nova Scotia during the 2003 study period, yielding a crude incidence of 2.24/100,000. The age-adjusted incident rate for 2003 was 2.13 (95% CI = 0.11-4.15). The age-adjusted rate for 1995 was 2.3 (95% CI = 0.08-4.53) while the age-adjusted rate for 1984 was 2.22 (95% CI = 0.13-4.32). Analysis of provincial health records identified 24 cases of ALS and an age-adjusted incidence of 2.44/100,000.

Conclusion:

The age-adjusted incidence of ALS in Nova Scotia has remained stable over the period 1984-2003. The incidence is similar to that reported in several other parts of the world.
Memory Performance in HIV/AIDS - A Prospective Case Control Study
Authors: Odiase Francis E. , Ogunrin Olubunmi A. , Ogunniyi Adesola A.
Published: December 2014

Background:

Memory impairment, usually impaired retrieval of information, has been described in HIV/AIDS, especially among those with severe illness. Neuro-cognitive disturbances in HIV/AIDS have been linked to poor quality of life and medication adherence. This prospective, case-control study was designed to assess the verbal and non-verbal memory as well as the attention abilities of Nigerian Africans with HIV/AIDS and correlate their performances with their CD4+ T lymphocytes (CD4+) counts.

Methods:

A total of 288 randomly selected subjects, comprising 96 HIV-positive symptomatic patients, 96 HIV-positive asymptomatic patients and 96 HIV-negative controls, participated in the study. The subjects were age-, sex-, and level of education matched. The Recognition Memory Test and Choice Reaction Time tasks, components of the computer-assisted neuropsychological tests battery- the Iron Psychology ‘FePsy’ were used for cognitive assessments.

Results:

The mean memory scores of the HIV-positive asymptomatic subjects did not differ significantly from the controls (p>0.05) but the HIV-positive symptomatic subjects' scores were significantly lower than the controls (p<0.05). Both HIV-positive groups had psychomotor slowing and impaired attention (p<0.05). The HIV-positive subjects with CD4+ counts <200/μl and between 200 and 499/μl had significant memory impairment (p<0.001 and p<0.001 respectively) but there was no significant impairment among those with count ≥500/μl. Impaired ability for sustained attention was however present irrespective of the CD4+ level relative to controls (p<0.001).

Conclusions:

We concluded that there was no significant memory disturbance among HIV-positive asymptomatic subjects despite the presence of impaired attention and psychomotor slowing, and that the severity of immune suppression (as indicated by the CD4+ T lymphocytes count) is a strong determinant of cognitive decline in HIV/AIDS.
Endoscopic Versus Microsurgical Resection of Third Ventricle Colloid Cysts
Authors: Grondin Ron T. , Hader Walter , MacRae M. Elizabeth , Hamilton Mark G.
Published: December 2014

Objective:

Endoscopic resection of colloid cysts has been performed as an alternative to microsurgical resection and stereotactic aspiration since 1982. To date, there are limited published studies comparing these procedures. In this study, we present the largest series of endoscopic resections published to date and compare outcomes to a cohort of microsurgical resections performed at the same institution.

Methods:

A retrospective chart review was conducted for all patients in the Calgary Health Region undergoing resection of a colloid cyst between 1991 and 2004. Comparison was made between patients treated with endoscopic resection versus microsurgical resection.

Results:

Twenty-five endoscopic and nine microsurgical procedures were performed. Complete resection was achieved in 24 of 25 procedures in the Endoscopic group, compared with all 9 procedures in the Microsurgical group. Patients in the Endoscopic group had a reduced operative time (mean 104 minutes versus 217 minutes) and reduced length of stay (3.8 days versus 8.4 days) compared to the Microsurgical group. One patient in the Endoscopic group had a complication (hemiparesis/pulmonary embolus). By contrast, 3 patients in the Microsurgical group had complications (seizure, ventriculitis/bone flap infection, and transient memory deficit). There was one recurrence in each group which both occurred at 5 years follow-up. The mean length of follow-up is 38 months in the Endoscopic group and 33 months in the Microsurgical group.

Conclusion:

Endoscopic resection of colloid cysts can be performed with significantly lower risk of complication than microsurgical resection and with equivalent surgical success. Operative time and length of hospital stay are both significantly reduced with endoscopic resection.
Treatment of Secondary Tonsillar Herniation by Lumboperitoneal Shunt Revision
Authors: Lam Fred C. , Wheatley Matthew B. , Mehta Vivek
Published: December 2014

Background:

Idiopathic intracranial hypertension (IIH) is a condition that usually affects young, obese women. Management is aimed at controlling symptoms of increased intracranial pressure (ICP) and prevention of visual failure due to papilledema. A common surgical treatment for IIH is the insertion of a lumboperitoneal shunt (LP shunt). Secondary symptomatic tonsillar herniation is an uncommon side effect following lumbar cerebrospinal fluid diversion.

Methods:

We present two cases of symptomatic secondary tonsillar herniation, one associated with a syrinx, in patients with IIH following valved LP shunting. Treatment options for this side effect may include transplanting the shunt to the ventricular system or decompression of the foramen magnum.

Results:

In our cases we elected to alter the construct of the LP shunt by inserting a programmable valve which led to clinical and radiological reversal of the tonsillar herniation as well as a dramatic reduction in an associated syrinx.

Conclusions:

When faced with LP shunt induced symptomatic secondary tonsillar herniation, consideration may be given to altering LP shunt dynamics, prior to inserting a ventricular catheter into normal sized ventricles or decompressing the posterior fossa.