bluuebunny/crossref_metadata_2025 huggingface dataset:
Subcortical Hyperexcitability in Migraineurs: A High-Frequency Oscillation Study
Authors: Lai Kuan-Lin , Liao Kwong-Kum , Fuh Jong-Ling , Wang Shuu-Jiun
Published: December 2014

Objective:

An abnormal central nervous system excitability level was found in patients with migraine. Whether it is hyper- or hypo-excitable is still debated. This study aimed to compare the somatosensory high-frequency oscillations (HFOs), which reflected subcortical excitability (early phase) and intracortical inhibition (late phase), between patients with migraine and control subjects.

Methods:

HFOs were recorded from C3'-Fz, using a 500-1000 Hz frequency filter after stimulation at right median nerves at the wrists, and divided into early and late phases based on the N20 peak. Fifty-nine untreated patients (n=24 during ictal period; n=35, interictal) and 22 controls finished the study.

Results:

In early HFOs, patients both during ictal and interictal periods had higher maximal amplitudes (p =0.039) and area-under-curve (p =0.029) than those of the controls. Regarding the late HFOs, there were no significant differences among these groups.

Conclusion:

Our study suggests a hyper-excitable state in the subcortical regions in patients with migraine both during interictal and ictal periods.
Interprofessional Stroke Rehabilitation for Stroke Survivors Using Home Care
Authors: Markle-Reid Maureen , Orridge Camille , Weir Robin , Browne Gina , Gafni Amiram , Lewis Mary , Walsh Marian , Levy Charissa , Daub Stacey , Brien Heather , Roberts Jacqueline , Thabane Lehana
Published: December 2014

Objective:

To compare a specialized interprofessional team approach to community-based stroke rehabilitation with usual home care for stroke survivors using home care services.

Methods:

Randomized controlled trial of 101 community-living stroke survivors (<18 months post-stroke) using home care services. Subjects were randomized to intervention (n=52) or control (n=49) groups. The intervention was a 12-month specialized, evidence-based rehabilitation strategy involving an interprofessional team. The primary outcome was change in health-related quality of life and functioning (SF-36) from baseline to 12 months. Secondary outcomes were number of strokes during the 12-month follow-up, and changes in community reintegration (RNLI), perceived social support (PRQ85-Part 2), anxiety and depressive symptoms (Kessler-10), cognitive function (SPMSQ), and costs of use of health services from baseline to 12 months.

Results:

A total of 82 subjects completed the 12-month follow-up. Compared with the usual care group, stroke survivors in the intervention group showed clinically important (although not statistically significant) greater improvements from baseline in mean SF-36 physical functioning score (5.87, 95% CI -3.98 to 15.7; p=0.24) and social functioning score (9.03, CI-7.50 to 25.6; p=0.28). The groups did not differ for any of the secondary effectiveness outcomes. There was a higher total per-person costs of use of health services in the intervention group compared to usual home care although the difference was not statistically significant (p = 0.76).

Conclusions:

A 12-month specialized, interprofessional team is a feasible and acceptable approach to community-based stroke rehabilitation that produced greater improvements in quality of life compared to usual home care. Clinicaltrials.gov identifier: NCT00463229
Pediatric Traumatic Retroclival Epidural Hematoma
Authors: McDougall Cameron M. , Sankar Tejas , Mehta Vivek , Pugh Jeffrey A.
Published: December 2014

A previously healthy ten-year-old girl was involved in a high speed motor vehicle accident (MVA) in which she was the belted front-seat passenger. The patient's teeth marks on the dashboard were evidence of a high-velocity impact. Her Glasgow Coma Score on scene was 13, and she was amnestic for the event. She was subsequently transported to the emergency room in full spinal precautions; on arrival she was hemodynamically stable with a Glasgow Coma Score of 14, complaining of neck and jaw pain. Neurological examination revealed impaired abduction of the right eye, with no other focal deficits. She had oral lacerations and bruising over the mandibles bilaterally.

Computed tomogram (CT) scan of the head was initially interpreted as normal, but on closer inspection demonstrated a 4mm retroclival hematoma (Figure 1). Sagittal CT through the upper cervical spine revealed the hematoma was epidural, bounded by the spheno-occipital synchondrosis superiorly and by the mid-body of the axis inferiorly (Figure 2). The odontoid was retroflexed (Figure 2). Bilateral mandibular fractures were also uncovered on facial imaging.
Stroke in Young Women
Authors: Salisbury Meredith , Pfeffer Gerald , Yip Samuel
Published: December 2014

In women ages 15-45 years, an additional set of risk factors are important in the pathogenesis of ischemic stroke. Some of these pertain strictly to women, and relate to exogenous hormones and pregnancy. Various other conditions are more common in women, which include migraine with aura, selected vascular disorders and autoimmune conditions. These differences do have implications for management in both the primary and secondary prevention of stroke in this age group.
Anatomical Variants of the Circle of Willis and Brain Lesions in Migraineurs
Authors: Cavestro C. , Richetta L. , L'Episcopo M. R. , Pedemonte E. , Duca S. , Di Pietrantonj C.
Published: December 2014

Background:

Some reports demonstrated vascular alterations in brain magnetic resonance imaging (MRI) in migraineurs and a relationship between circle of Willis (Circle) variants and lacunar brain infarcts. We examined anomalies of the whole circle of Willis and their relationship with vascular brain lesions in migraineurs, to identify any possible vascular mechanism in migraine.

Methods:

We studied, with a cohort controlled study, the circle of Willis in migraineurs seen consecutively in our Headache Center, and in non-headache controls, using angio-MRI of the brain. Statistical analysis used ANOVA, Scheffè's criterion, t-student test.

Results:

We recruited 270 migraineurs (204 without aura (MWOA), 66 with aura (MWA) and 159 controls. Migraineurs presented an anatomical variant in 108 (40%) cases with 34 controls (21.4%) presenting a variant. We found a significant association between MWOA and variants (OR=2.4 CI95% [1.5 to 3.9]) and between MWA and variants (OR=3.2 CI95% [1.6 to 4.1]). Unilateral posterior variants with basilar hypoplasia are statistically associated only with MWA compared to controls (OR=9.2, CI95% [2.3 to 37.2]). Thirty-three percent of MWOA and 24% of MWA sufferers present some kind of brain lesion, included 2% of infra-tentorial lesions. We did not find any statistical association between the presence of Circle variants and ischemic lesions on MRI (OR=1.5 CI95% [0.68; 1.94]), or with infratentorial lacunar lesions (OR=1.58 CI95% [0.48 to 5.24]).

Conclusions:

Anatomical variants of the Circle of Willis are significantly more frequent in migraineurs; posterior anomalies are more frequent in MWA, suggesting a vascular mechanism provoking changes in cerebral blood flow, thereby stimulating cortical spreading depression.
Meta-Analysis of Aldehyde Dehydrogenase 2 Gene Polymorphism and Alzheimer's Disease in East Asians
Authors: Hao Pan-Pan , Chen Yu-Guo , Wang Jia-Li , Wang Xing Li , Zhang Yun
Published: December 2014

Background:

The association of genetic polymorphism of mitochondrial aldehyde dehydrogenase 2 (ALDH2) and Alzheimer's disease (AD) has been controversial and has been investigated only in several small-sample studies. In the present study, we performed a meta-analysis to evaluate the cross-sectional association ofALDH2variants and AD risk in East Asian populations.

Methods:

Trials were retrieved through MEDLINE, EMBASE, J-STAGE and the China National Knowledge Internet databases (from January 1, 1994 to November 1, 2010) without any restriction on language. Data were abstracted by a standardized protocol.

Results:

We found four studies of 821AD patients and 1380 healthy controls that qualified for the analysis. The variantALDH2genotype GA/AA was not associated with increased AD risk (odds ratio (OR) = 1.35; 95% confidence interval (CI) = 0.75-2.42; p = 0.32), even after stratification for the status of apolipoprotein E epsilon 4 allele. However, in the subgroup analyses, the association was significant for men (OR = 1.72; 95% CI = 1.10-2.67; p = 0.02).

Conclusions:

This study adds to the evidence thatALDH2GA/AA genotype increases the risk of AD among East Asian men, although the effect size is moderate.
An Interesting Case of Nuchal Rigidity
Authors: Boettcher Christina , Warnke Clemens , Macht Stephan , Hartung Hans-Peter , Kieseier Bernd C.
Published: December 2014

A 34 year-old female without prior relevant medical history presented to our emergency room with a two-day history of neck pain, odynophagia and elevated body temperature up to 38.2° C. Her general practitioner had started the patient on antibiotic treatment with ciprofloxacin and referred her to our emergency department for further diagnostic workup and treatment of suspected meningitis. Initial neurological examination revealed neck rigidity and head pain without further focal neurological signs. Body temperature was 37.7 °C, blood analyses revealed a normal leukocyte count (8.900/μl) and normal C-reactive protein (<0.3mg/dl), blood cultures were sterile. Lumbar puncture was without pathological findings (<1 leukocytes/μl, normal levels for glucose, lactate and protein). Cervical magnetic resonance imaging could rule out osseous injury and cervical myelopathy, however a small prevertebral, retropharyngeal fluid collection was visible (Figure 1a-c). This prompted the diagnosis of acute retropharyngeal calcific tendinitis (RCT). This diagnosis was confirmed by conventional x-ray showing the presence of a characteristic amorphous calcification in the retropharyngeal space anterior to the C1-C2 segments (Figure 1d). Treatment with i.v. methylprednisolone (250mg) was started and pain was reduced shortly after the first infusion. The patient was discharged on tapered oral methylprednisolone and non-steroidal anti-inflammatory drug (NSAID) treatment. Symptoms resolved completely within a week.
ARAC - The Montreal Jewish General Hospital Alzheimer Risk Assessment Clinic
Authors: Schipper Hyman M. , Liberman Adrienne , Kelner Nora , Babins Lennie , Fried Lynda , Bilbul Melanie , Goodman Rachel
Published: December 2014

Introduction:

In parallel with robust efforts world-wide to develop effective neuroprotection for established disease, resources are being mobilized to delineate risk factors and implement preventive measures in a concerted effort to forestall the anticipated Alzheimer disease (AD) epidemic. A review of heritable and ‘acquired’ dementia risk factors, many operating at midlife, is presented in a companion paper.

Objectives:

In 2009, an Alzheimer Risk Assessment Clinic (ARAC) was established at the Jewish General Hospital (Montreal) to address the concerns increasingly being voiced by active middle-aged individuals at risk for AD. A positive family history of AD and/or perceived changes in personal cognitive function (predominantly short-term memory) are main reasons for referral. The primary objectives of ARAC are to (i) ascertain, inform and mitigate the risks of developing AD in cognitively-healthy persons aged 40-65 based on best available medical and epidemiological evidence, (ii) conduct scientific research on midlife dementia risk and prevention in this population and (iii) provide instruction in dementia risk assessment and management to health professionals, clinical/research fellows, medical residents and students. ARAC infrastructure, evaluation protocol, risk profile classification scheme, interventions, knowledge dissemination program, case vignettes, and seminal research projects are described.

Conclusions:

It is hoped that ARAC and similar initiatives will help prevent or delay dementia by innovating effective interventions based on increasingly nuanced estimation of modifiable AD risk in presymptomatic persons.
Primary or Secondary Decompressive Craniectomy: Different Indication and Outcome
Authors: Al-Jishi Ahmed , Saluja Rajeet Singh , Al-Jehani Hosam , Lamoureux Julie , Maleki Mohammad , Marcoux Judith
Published: December 2014

Background:

Intracranial hypertension can cause secondary damage after a traumatic brain injury. Aggressive medical management might not be sufficient to alleviate the increasing intracranial pressure (ICP), and decompressive craniectomy (DC) can be considered. Decompressive craniectomy can be divided into categories, according to the timing and rationale for performing the procedure: primary (done at the time of mass lesion evacuation) and secondary craniectomy (done to treat refractory ICP). Most studies analyze primary and secondary DC together. Our hypothesis is that these two groups are distinct and the aim of this retrospective study is to evaluate the differences in order to better predict outcome after DC.

Methods:

Seventy patients had DC over a period of four years at our center. They were divided into two groups based on the timing of the DC. Primary DC (44 patients) was done within 24 hours of the injury for mass lesion evacuation. Secondary DC (26 patients) was done after 24 hours and purely for the treatment of refractory ICP. Pre-op characteristics and post-op outcomes were compared between the two groups.

Results:

There was a significant difference in the mechanism of injury, the pupil abnormalities and Marshall grade between primary and secondary DC. There was also a significant difference in outcome with primary DC showing 45.5% good outcome and 40.9% mortality and secondary DC showing 73.1% good outcome and 15.4% mortality.

Conclusions:

Primary and secondary DC have different indications and patients characteristics. Outcome prediction following DC should be adjusted according to the surgical indication.
2-Methoxyestradiol Attenuates Autophagy Activation After Global Ischemia
Authors: Xin Xiao-Yu , Pan Jing , Wang Xiao-Qiang , Ma Jian-Fang , Ding Jian-Qing , Yang Guo-Yuan , Chen Sheng-Di
Published: December 2014

Background:

Hypoxia inducible factor 1 (HIF-1) is a key transcriptional factor activated during cerebral ischemia, which regulates a great number of downstream genes, including those associated with cell death. In the present study, we aimed to test the hypothesis that post-ischemic HIF-1α up-regulation might promote autophagy activation; thereby, HIF-1α inhibitor 2ME2 might prevent neurons from ischemic injury through inhibiting autophagy.

Methods:

Global ischemia was induced using the four-vessel occlusion model (4-VO) in Sprague-Dawley rats (male, 250-280g). 2-Methoxyestradiol (2ME2, 5mg/kg, i.p.) was administrated to down-regulate HIF-1α expression. Post-ischemic beclin-1 and LC3 protein expression was determined at different time points through Western blot assay. Neuronal injury was determined by cresyl violet staining and TUNEL staining in coronal histological sections.

Results:

The expression of beclin-1 and the ratio of LC3-II/LC3-I increased significantly at 12 and 24 h after ischemia. 2ME2 could remarkably inhibit the up-regulation of beclin-1 and the increase of LC3-II/LC3-I ratio during reperfusion. Moreover, 2ME2 and 3-MA exhibited powerful protective effects against ischemic/reperfusion induced neuronal injury.

Conclusions:

This study confirmed that autophagy participated in post-ischemic neuronal injury. 2ME2, a HIF-1α inhibitor, might significantly decrease autophagy activation after cerebral ischemia and relieve post-ischemic neuronal injury. Our findings demonstrate that autophagy could be a potential target for neuronal protection after cerebral ischemia.
Neuroscience in Nazi Europe Part II: Resistance against the Third Reich
Authors: Zeidman Lawrence A.
Published: December 2014

Previously, I mentioned that not all neuroscientists collaborated with the Nazis, who from 1933 to 1945 tried to eliminate neurologic and psychiatric disease from the gene pool. Oskar and Cécile Vogt openly resisted and courageously protested against the Nazi regime and its policies, and have been discussed previously in the neurology literature. Here I discuss Alexander Mitscherlich, Haakon Saethre, Walther Spielmeyer, Jules Tinel, and Johannes Pompe. Other neuroscientists had ambivalent roles, including Hans Creutzfeldt, who has been discussed previously. Here, I discuss Max Nonne, Karl Bonhoeffer, and Oswald Bumke. The neuroscientists who resisted had different backgrounds and motivations that likely influenced their behavior, but this group undoubtedly saved lives of colleagues, friends, and patients, or at least prevented forced sterilizations. By recognizing and understanding the actions of these heroes of neuroscience, we pay homage and realize how ethics and morals do not need to be compromised even in dark times.
Aspirin Treatment Increases the Risk of Cerebral Microbleeds
Authors: Ge Lihong , Niu Guangming , Han Xiaodong , Gao Yang , Wu Qiong , Wu Hui , Zhang Ying , Guo Dongling
Published: December 2014

Background:

The objective of the study was to determine the frequency of cerebral microbleeds (CMBs) by using phasesensitive imaging in patients with previous transient ischemic attack (TIA) or stroke who were receiving aspirin treatment.

Methods:

We retrospectively analyzed 300 outpatients with ischemic cerebrovascular disease: 150 had been receiving aspirin treatment for >1 year (patients), and 150 controls had not previously received aspirin. Cerebral microbleeds were defined by a trained observer (blinded to clinical details) according to results of T2-weighted, T1-weighted, diffusion-weighted, and phase-sensitive magnetic resonance imaging (MRI). Numerous vascular risk factors including white matter hyperintensity (WMH), duration of aspirin treatment, age, hypertension or diabetes mellitus were investigated for a possible association with the presence of CMBs in the two groups.

Results:

The frequency of CMBs (60/150 (40%) vs 18/150 (12%); odds ratio 4.899, p <0.0001) and intracerebral hemorrhage (ICH)(42/150 (28%) vs 2/150 (1%); odds ratio 28.778, p <0.0001) were significantly higher in the patients than in the controls. Among patients, those using aspirin for >5 years(42/68 (62%) showed a higher frequency of CMBs than those receiving aspirin for ≤ 5 years(18/82 (22%); odds ratio 5.744, p<0.0001). WMH (p=0.020/0.030, 0.007/0.000) age (p=0.007/0.000) and hypertension (p=0.000/0.033), in patients and controls respectively, were each associated with CMBs.

Conclusions:

There was a clear impact of aspirin treatment on CMBs associated with intracerebral hemorrhage in Chinese patients. The frequency of CMBs and hemorrhagic complications was higher in patients treated with long-term aspirin.
A Critical Look at Phenytoin Use for Early Post-Traumatic Seizure Prophylaxis
Authors: Debenham Sierra , Sabit Behzad , Saluja Rajeet S. , Lamoureux Julie , Bajsarowicz Paul , Maleki Mohammad , Marcoux Judith
Published: December 2014

Backround:

The American Academy of Neurology recommended using phenytoin or carbamazepine to prevent early post-traumatic seizures (PTS) in severe traumatic brain injuries (TBI). In this study, we examined the effects of using phenytoin prophylaxis on mild, moderate, and severe TBIs. There have been no studies looking at compliance rate and side effects of systematic use of phenytoin at a large population scale. The goal of this study is to determine 1) the proportion of TBI patients receiving phenytoin prophylaxis; 2) which parameters decided when to decide administer phenytoin; 3) prophylaxis efficacy and complication rate.

Methods:

We retrospectively studied all patients admitted with a TBI over a two year-period and collected the following information: age, GCS score, CT-scan Marshall grade, incidence of early PTS, incidence of phenytoin use and time delay, side effects, and incidence of over-dosage or under-dosage.

Results:

1008 patients were included. 5.4 % had early PTS, 2.3 % while on prophylaxis and 3.1% while not on prophylaxis, 1.9% before reaching the hospital and 1.2% prior to phenytoin administration while in hospital. Delay of administration was 5 hours. 64.8% received prophylaxis and physicians used positive CT scan as the primary decision-making parameter (p<.001). Compliance with guidelines was 99.7%. Adverse reactions occurred in 0.5%. Levels were drawn in 42.2% (52% therapeutic, 41% low, 7% high).

Conclusions:

Phenytoin is used according to guidelines, with CT scan being the main decision factor for its use. The frequency of early PTS rate is low and side effects are rare. However, earlier administration of phenytoin and adequate levels could further prevent early PTS.
Inflammatory Demyelinating Brain Lesions Heralding Primary CNS Lymphoma
Authors: Husseini Leila , Saleh Andreas , Reifenberger Guido , Hartung Hans-Peter , Kieseier Bernd C.
Published: December 2014

Brain biopsy plays a crucial role in the exploration of suspect white matter lesions in the differential diagnosis of primary central nervous system lymphoma (PCNSL) and inflammatory demyelination. We present the case of a previously healthy, immunocompetent woman, aged fifty-nine, who developed a histologically confirmed demyelinating white matter lesion months prior to the manifestation of a PCNSL. Similar cases of “sentinel lesions” preceding a PCNSL have been reported. In a literature review, we compared the diagnostic features that may be useful to differentiate a PCNSL from inflammatory demyelinating disease in older age. We conclude that the occurrence of large, contrast-enhancing cerebral lesions in older patients with a relapsing-remitting disease course and steroid-resistant vision disorders should lead to the consideration of a PCNSL.
Growing Up With Cerebral Palsy: Contemporary Challenges of Healthcare Transition
Authors: Oskoui Maryam
Published: December 2014

Cerebral palsy is traditionally known as a major cause of chronic disability in childhood. With advances in neonatal care and improved survival, the majority of adolescents with cerebral palsy require ongoing services into adulthood. This paper highlights some of the challenges in their transition from pediatric to adult healthcare and proposes key elements to ensure a smooth transition process.
Predictors of Survival in a Huntington's Disease Population from Southern Italy
Authors: Rinaldi Carlo , Salvatore Elena , Giordano Ilaria , De Matteis Sara , Tucci Tecla , Cinzia Valeria Russo , Rossi Fabiana , Castaldo Imma , Morra Vincenzo Brescia , Di Maio Luigi , Filla Alessandro , De Michele Giuseppe
Published: December 2014

Background:

The primary aim of the present study was to determine the survival rates and identify predictors of disease duration in a cohort of Huntington's disease (HD) patients from Southern Italy.

Methods:

All medical records of HD patients followed between 1977 and 2008 at the Department of Neurological Sciences of Federico II University in Naples were retrospectively reviewed and 135 patients were enrolled in the analysis. At the time of data collection, 41 patients were deceased (19 males and 22 females) with a mean ± SD age at death of 56.6 ± 14.9 years (range 18-83).

Results:

The median survival time was 20 years (95% CI: 18.3-21.7). Cox regression analysis showed that the number of CAG in the expanded allele (HR 1.09 for 1 point triplet increase, p=0.002) and age of onset (HR 1.05 for 1 point year increase, p=0.022) were independent and significant predictors of lower survival rates.

Conclusions:

We believe that these findings are important for a better understanding of the natural history of the disease and may be relevant in designing future therapeutic trials.
Recurrent Encephalopathy: NAGS (N-Acetylglutamate Synthase) Deficiency in Adults
Authors: Cartagena A. , Prasad A.N. , Rupar C.A. , Strong M. , Tuchman M. , Mew N. Ah , Prasad C.
Published: December 2014

N-acetyl-glutamate synthase (NAGS) deficiency is a rare autosomal recessive urea cycle disorder (UCD) that uncommonly presents in adulthood. Adult presentations of UCDs include; confusional episodes, neuropsychiatric symptoms and encephalopathy. To date, there have been no detailed neurological descriptions of an adult onset presentation of NAGS deficiency. In this review we examine the clinical presentation and management of UCDs with an emphasis on NAGS deficiency. An illustrative case is provided. Plasma ammonia levels should be measured in all adult patients with unexplained encephalopathy, as treatment can be potentially life-saving. Availability of N-carbamylglutamate (NCG; carglumic acid) has made protein restriction largely unnecessary in treatment regimens currently employed. Genetic counselling remains an essential component of management of NAGS.
Serum Urate and the Risk of Parkinson's Disease: Results From a Meta-Analysis
Authors: Shen Chunhong , Guo Yi , Luo Wei , Lin Chen , Ding Meiping
Published: December 2014

Objective:

Serum urate may exert protective effects against Parkinson's disease (PD) through its antioxidant capacities. In this article, we examine the hypothesis that high serum urate levels are associated with lower risk of PD.

Methods:

We searched NCBI (PubMed), ISI Web of Science and EMBASE for studies that reported the risk of PD associated with serum urate. Fixed or random effects meta-analysis was used to pool results across studies, and further analysis was used to assess the effects by gender.

Results:

Six studies met the inclusion criteria involving a total of 33 185 participants. Overall, we found a 33% reduction in PD incidence among persons with high serum urate level (relative risk [RR]=0.67; 95% confidence interval [CI], 0.50-0.91). Subgroup analysis was performed with 20 641 men and 12 544 women included, indicating statistically significant protective effects of serum urate in men (RR=0.60; 95% CI, 0.40-0.90) but not in women. A dose-response trend of serum urate to reduce PD risk was also observed involving 11 795 participants (RR=0.77; 95% CI, 0.68-0.88). Additionally, high serum urate levels seemed to slow the clinical decline of PD patients (RR=0.56; 95% CI, 0.43-0.72).

Conclusions:

In light of these findings, our study confirms previous findings of a robust association between high serum urate level and PD risk, especially in men. It also suggests that long-term exposure to high serum urate may be linked to the delay of PD progression, however more well-designed investigations are needed.
Status Epilepticus: A Review, With Emphasis on Refractory Cases
Authors: Hunter Gary , Young G. Bryan
Published: December 2014

Status epilepticus is among the most dramatic of clinical presentations encountered by emergency room physicians, neurologists, neurosurgeons and intensivists. While progress in its management has been aided significantly with an increasing number of effective treatment options, improved diagnostic methods and more effective monitoring, poor outcomes and diagnostic failures are still frequently encountered. Refractory cases still carry significant morbidity and mortality rates, including poor cognitive outcomes. This review discusses basic pathophysiology and management of status epilepticus, neuroimaging findings, the role of continuous electroencephalogram monitoring and nonconvulsive status epilepticusas well as recent developments in treatment options for refractory cases.
Patients Referred for TIA May Still Have Persisting Neurological Deficits
Authors: Moreau Francois , Jeerakathil Thomas , Coutts Shelagh B. ,   FRCPC for the ASPIRE investigators
Published: December 2014

Background:

The presence of residual neurological deficits after neurological symptoms is important information for making a diagnosis of Transient Ischemic Attack (TIA) versus stroke. The purpose of this study was to establish the reliability of the referring physician (non neurologist) to report focal neurological deficits in the context of an urgent referral for TIA.

Methods:

Prospectively recorded urgent physician-to-physician phone referrals for TIA through the Southern Alberta TIA hotline from March 2009 to July 2010 were reviewed. “Has the neurological deficit completely resolved?” was asked to the referring physician (family or emergency room physician) and recorded prospectively as a yes/no response. Patients were included if a neurological examination was performed by a neurologist on the same day as referral. The neurologist's assessment of whether the deficit had resolved was compared to that of the referring physician.

Results:

78 patients were included in this study. 62 patients had resolved as per the referring physician's assessment. Of these 62 patients, 16 (25.8% 95%CI 16-38) had evidence of persisting neurological deficits on the neurologist's assessment. A wide variety of mild neurological deficits were identified. None of these deficits appeared to be explained by progression of symptoms.

Conclusion:

Physicians referring patients with TIA syndromes for emergent assessment do not reliably detect mild residual deficits in one-quarter of patients. We are questioning the validity of neurological deficit resolution as a triage rule. The findings suggest that studies of TIA likely include a proportion of minor stroke patients and this should be remembered when extrapolating the results to other populations.
Increased Intestinal Permeability and Parkinson Disease Patients: Chicken or Egg?
Authors: Salat-Foix D. , Tran K. , Ranawaya R. , Meddings J. , Suchowersky O.
Published: December 2014

Gastrointestinal involvement is a frequent and early event in the course of Parkinson Disease (PD), and may have a prominent role in the early pathophysiology of the disease. On the other hand, derangement in intestinal permeability could also result from the involvement of the gastrointestinal tract over the course of the disease.

Patients and methods:

The intestinal permeability of 12 non-selected PD patients was studied using a validated, non-invasive test; these results were compared to predefined age-adjusted reference values.

Results:

4/12 PD patients had abnormal gastrointestinal permeability; two had both an abnormal lactulose/mannitol ratio and an abnormal sucrose concentration, and two an isolated abnormal result. An increased lactulose/mannitol ratio is consistent with defect of either the enterocytes or the tight junctions between them.

Conclusion:

Intestinal permeability is increased in a significant proportion of unselected PD patients with minimal gastrointestinal symptoms. The significance of this finding needs to be further evaluated.
Effects of Creatine and Exercise on Skeletal Muscle of FRG1-Transgenic Mice
Authors: Ogborn Daniel I. , Smith Katelyn J. , Crane Justin D. , Safdar Adeel , Hettinga Bart P. , Tupler Rossella , Tarnopolsky Mark A.
Published: December 2014

Background:

The FRG1-transgenic mouse displays muscle dysfunction and atrophy reminiscent of fascioscapulohumeral muscular dystrophy (FSHD) and could provide a model to determine potential therapeutic interventions.

Methods:

To determine if FRG1 mice benefit from treatments that improve muscle mass and function, mice were treated with creatine alone (Cr) or in combination with treadmill exercise (CrEX).

Results:

The CrEx treatment increased quadriceps weight, mitochondrial content (cytochome c oxidase (COX) activity, COX subunit one and four protein), and induced greater improvements in grip strength and rotarod fall speed. While Cr increased COX subunits one and four protein, no effect on muscle mass or performance was found. Since Cr resulted in no functional improvements, the benefits of CrEx may be mediated by exercise; however, the potential synergistic action of the combined treatment cannot be excluded.

Conclusion:

Treatment with CrEx attenuates atrophy and muscle dysfunction associated with FRG1 overexpression. These data suggest exercise and creatine supplementation may benefit individuals with FSHD.
Epileptiform Activity in Neurocritical Care Patients
Authors: Kramer Andreas H. , Jette Nathalie , Pillay Neelan , Federico Paolo , Zygun David A.
Published: December 2014

Background:

Non-convulsive seizures have been reported to be common in neurocritical care patients. Many jurisdictions do not have sufficient resources to enable routine continuous electroencephalography (cEEG) and instead use primarily intermittent EEG, for which the diagnostic yield remains uncertain. Determining risk factors for epileptiform activity and seizures could help identify patients who might particularly benefit from EEG monitoring.

Methods:

We performed a cohort study involving neurocritical care patients with admission Glascow Coma Scale (GCS) scores =≤ 12, who underwent ≥ 1 EEG. EEGs were reviewed for presence of interictal discharges, periodic epileptiform discharges (PEDs), and seizures. Multivariate analysis was used to identify predictors of these findings and to describe their prognostic implications.

Results:

393 patients met inclusion criteria. 34 underwent cEEG, usually because epileptiform activity was first detected on a routine EEG. The prevalence of PEDs or electrographic seizures was 13%, and was highest with anoxic encephalopathy and central nervous system infections. Other independent predictors for epileptiform activity included a history of convulsive seizure(s), increasing age, deeper coma, and female gender. Although patients with epileptiform activity had higher mortality, this association disappeared after adjustment for confounders.

Conclusion:

Approximately 7-8 neurocritical care patients must undergo intermittent EEG monitoring in order to diagnose one with PEDs or seizures. The predictors we identified could potentially help guide use of resources. Repeated intermittent studies, or cEEG, should be considered in patients with multiple risk factors, or when interictal discharges are identified on an initial EEG. It remains unclear whether aggressive prevention and treatment of electrographic seizures improves neurologic outcomes.
Concussion Knowledge among Medical Students and Neurology/Neurosurgery Residents
Authors: Boggild Miranda , Tator Charles H.
Published: December 2014

Background and Objectives:

Concussion is a prevalent brain injury in the community. While primary prevention strategies need to be enhanced, it is also important to diagnose and treat concussions expertly and expeditiously to prevent serious complications that may be life-threatening or long lasting. Therefore, physicians should be knowledgeable about the diagnosis and management of concussions. The present study assesses Ontario medical students’ and residents’ knowledge of concussion management.

Methods:

A survey to assess the knowledge and awareness of the diagnosis and treatment of concussions was developed and administered to graduating medical students (n= 222) and neurology and neurosurgery residents (n = 80) at the University of Toronto.

Results:

Residents answered correctly significantly more of the questions regarding the diagnosis and management of concussions than the medical students (mean = 5.8 vs 4.1, t= 4.48, p<0.01). Gender, participation in sports, and personal concussion history were not predictive of the number of questions answered correctly. Several knowledge gaps were identified in the sample population as a whole. Approximately half of the medical students and residents did not recognize chronic traumatic encephalopathy (n = 36) or the second impact syndrome (n = 44) as possible consequences of repetitive concussions. Twenty-four percent of the medical students (n = 18) did not think that “every concussed individual should see a physician” as part of management.

Conclusions:

A significant number of medical students and residents have incomplete knowledge about concussion diagnosis and management. This should be addressed by targeting this population during undergraduate medical education.
Diabetes, Intracranial Stenosis and Microemboli in Asymptomatic Carotid Stenosis
Authors: Lam Thach D. , Lammers Stephanie , Munoz Claudio , Tamayo Arturo , Spence J. David
Published: December 2014

Background:

The risk of stroke in patients with asymptomatic carotid stenosis (ACS) is now so low that it is important to have methods to identify those patients most likely to benefit from intervention, or who may require special consideration in choice of medical therapy. We studied the prediction of stroke, death or transient ischemic attacks (stroke/death/TIA) in patients with ACS by intracranial arterial stenosis, and microemboli on transcranial Doppler (TCD), and the effect of diabetes mellitus on microemboli, intracranial stenosis and risk of events.

Methods:

Patients with ACS > 60% by Doppler ultrasound were recruited from the Stroke Prevention Clinic of University Hospital, London, Canada. All 339 participants underwent TCD for detection of intracranial stenosis and detection of microemboli, and carotid ultrasound to measure extracranial stenosis and total carotid plaque area. Participants were followed for three years, to determine the risk of stroke/death/TIA.

Results:

Stroke/death/TIA occurred in 38% of patients with microemboli versus 10% without (p=0.0001), and in 18% of patients with intracranial stenosis, versus 10% without (p=0.042). Diabetics were significantly more likely to have intracranial stenosis (45% vs. 29%, p =0.014), microemboli (38% vs. 10%, p <0.0001), and had significantly higher risk of stroke/death/TIA over three years (21% vs. 11% without; p=0.024). Survival free of stroke, TIA or death was significantly better without microemboli or intracranial stenosis (p<0.0001).

Conclusions:

Diabetes, microemboli and intracranial stenosis predicted higher risk of stroke, death or TIA than did extracranial stenosis or total plaque area; diabetics may need more intensive therapy.
Long-term Results of Radiosurgery for Cerebral Arteriovenous Malformations
Authors: Lecavalier-Barsoum Magali , Roy Daniel , Doucet Robert , Fortin Bernard , Lambert Carole , Moumdjian Robert , Bahary Jean-Paul
Published: December 2014

Background:

Stereotactic radiosurgery (SRS) is known to safely result in a high obliteration rate for small and medium sized arteriovenous malformations (AVM).

Objective:

To evaluate the long-term outcome of patients treated with SRS, with special emphasis given to obliteration and toxicity rates.

Methods:

We performed a review of 43 cerebral AVM patients, treated from 1998 to 2008 with a single SRS dose ranging from 21-25 Gy. Of these, 37 had a minimal follow-up of one year. Medical files were reviewed to assess patient and AVM characteristics, the SRS treatment, therapy prior to SRS, the obliteration rate and toxicities. Whenever necessary, outcome data was supplemented by telephone interviews with the patient or treating physician.

Results:

AVM size was ≥3cm in diameter in 21% of patients. Five patients (11.6%) underwent surgery prior to SRS and 31 patients (72.1%) received one or more embolizations prior to SRS. Of the patients followed with angiography ≥1 year post-SRS, 89% (33/37) had a complete obliteration of the nidus, after a median time of 24.7 months post-treatment. Embolization prior to SRS was not predictive of outcome. One patient suffered a non-fatal haemorrhage between treatment and obliteration. The rate of symptomatic radiation-induced radiological changes was 8.1%.

Conclusion:

Our study shows both obliteration and complication rates in the upper limit of those reported in the literature. SRS seems an attractive treatment option for small AVMs. Unlike other reports, the prior use of embolization did not impact negatively on obliteration rates.
The Syndrome of Infantile-Onset Saccade Initiation Delay
Authors: Salman Michael S. , Ikeda Kristin M.
Published: December 2014

Introduction:

Infantile-onset saccade initiation delay (ISID), also known as congenital ocular motor apraxia, is characterized by the inability to initiate volitional horizontal saccades. Other abnormalities including developmental delay and ataxia have been reported. The frequency of these abnormalities is unknown. We performed a detailed review of the medical literature to quantify features of ISID.

Methods:

We searched the English medical literature for articles related to ISID from 1952 to 2010. Whenever possible, patients were excluded if they had acquired SID, Joubert syndrome or neurodegenerative conditions. The minimum prevalence was calculated for each abnormality.

Results:

Sixty-six articles with information on 288 patients were included in the analysis. Head thrusts were reported in 84.7%. Blinks without head thrusts were used to initiate saccades in 41%. The fast phases of the optokinetic response and vestibulo-ocular reflex were impaired in 69.8% and 34.4% respectively. Smooth ocular pursuit was abnormal in 33%. Global developmental delay occurred in 41.3%, speech or language delay in 36.5%, cognitive delay in 17%, hypotonia in 35.8%, motor delay in 48.6%, and ataxia/clumsiness in 49.3% of patients. Neuroimaging was performed on 197 patients and was normal in 39.1%. Abnormalities involved the cerebellum (24.9%), cerebrum (15.7%), other infratentorial structures (11.7%), and corpus callosum (6.1%).

Conclusions:

Infantile-onset saccade initiation delay is frequently associated with deficits in reflexive saccades and less frequently with impaired smooth ocular pursuit. Developmental delay, hypotonia, and ataxia occur frequently in ISID, suggesting more global brain impairment and not just a saccadic disorder.
Experiences with the Execution of Intercultural, Intercontinental Trials - Part I
Authors: Barnett H. J. M.
Published: December 2014

Large scale, international clinical trials are formidable challenges, but they are the most effective means of answering important clinical questions in a definitive, generalizable manner. They require adequate funding and must be rigorously conducted. Much can be gleaned from such studies, which address the important research questions and provide answers to related questions. Such trials are enormously rewarding and are worth the expense and effort.
Impact of Technique on Cushing Disease Outcome Using Strict Remission Criteria
Authors: Alahmadi Hussein , Cusimano Michael D. , Woo Kenneth , Mohammed Ameen A. , Goguen Jeannette , Smyth Harley S. , Macdonald Robert L. , Muller Paul J. , Horvath Eva , Kovacs Kalman
Published: December 2014

Background:

Cushing disease (CD) constitutes a challenging condition for the pituitary surgeon. Given the variety of factors affecting outcomes in CD, it is uncertain whether the newer endoscopic technique improves the results of surgery.

Methods:

A review was conducted of CD cases at our institution between 2000 and 2010. Analysis was done to: determine if surgical technique had an effect on outcome, identify the predictors of outcome and provide details of failed cases. Remission was defined as normal postoperative 24-hour urinary free cortisol (24-h UFC), suppression of morning serum cortisol to <50 nmol/L after 1mg of dexamethasone or being dependent on steroid replacement.

Results:

Forty-two patients met our inclusion criteria. Average follow-up period was 33 months. There were 15 macroadenomas and 27 microadenomas. Seventeen patients had an endoscopic transsphenoidal surgery and twenty-five patients had a microscopic transsphenoidal procedure. Long-term overall remission was achieved in 26 (62%) patients. There was no significant difference in remission rates between the two techniques (p value 0.757). Patient's subjective symptomatic improvement and drop of morning serum cortisol in the postoperative period to less than 100 nmol/L correlated with long-term remission (p value 0.0031and 0.0101, respectively) while repeat surgery was the only predictor of the lack of postoperative remission (p value 0.0008).

Conclusions:

Revision surgery predicted poor remission rate for CD. Within the power of our study size, there was no difference in outcome between the endoscopic and microscopic approaches. Surgical outcomes should be reviewed in association with remission criteria used in a study.
Correlation Between MRI Findings and Histological Diagnosis of Brainstem Glioma
Authors: Yin Luxin , Zhang Liwei
Published: December 2014

Objective:

In most studies, treatment decisions of brainstem glioma are based solely on MRI features and do not incorporate a histopathological diagnosis. In the current study, we sought to compare MRI characteristics with histopathological findings of bainstem glioma.

Methods:

From April 2003 through April 2012, 150 patients were diagnosed with brainstem gliomas by MRI and microsurgically treated in Tiantan Hospital, Beijing, China. All the MRI and histopathological findings of these patients were respectively reviewed.

Results:

Of the 150 patients, 65 were female and 85 were male, 120 were adults and 30 were children (age < 18 years), 108 were low-grade glioma (72.0%), 35 were high-grade glioma (23.3%). The accuracy of the MRI diagnosis for brainstem glioma was 95.3%. Data analysis of the MRI findings revealed that a focal lesion was associated with a more favorable histopathological diagnosis in intrinsic (P=0.005) and exophytic (P=0.001) brainstem glioma patients. In the intrinsic diffuse type, tumors without enhancement had more favorable pathological findings (P=0.009).

Conclusions:

To our knowledge, this is the largest case series of this nature reported in the literature to date. The results of this study suggest that MRI features of brainstem gliomas could predict some pathological features and guide prognosis, choice of biopsy and treatment modalities. The pathology of tumors with a focal appearance on MRI was associated with a prognosis that was significantly better than their diffuse counterparts. For the intrinsic diffuse gliomas, non-enhancing tumors had pathology suggestive of a favorable prognosis.
Size Ratio: A Morphological Factor Predictive of the Rupture of Cerebral Aneurysm?
Authors: Li Meihua , Jiang Zhiqun , Yu Huiqiang , Hong Tao
Published: December 2014

Background:

Determining factors predictive of the natural risk of rupture of cerebral aneurysms is difficult. We studied morphological factors associated with rupture in a study model of patients with mirror location intracranial aneurysms, one aneurysm that had ruptured and one that had not, each patient served as their own control attempting to eliminate confounding variables.

Methods:

We collected five one-dimensional measurements and four two-dimensional indices from three-dimensional rotational digital subtraction angiography images of patients in the proposed study model and explored their correlation with aneurysm rupture. Parameters were analyzed with a paired Student's t test for significance and significant parameters were further examined by multivariate conditional logistic regression analysis.

Results:

Fifty-two patients with 52 pairs of intracranial aneurysms in a mirror location were studied. The maximum perpendicular height, neck diameter, maximum width, maximum height, aspect ratio, size ratio, and bottleneck factor were significantly associated with ruptured aneurysms on bivariate analysis. A logistic regression analysis showed that only size ratio, which was defined as the ratio of the maximal height to parent artery average diameter, is independently correlated with ruptured intracranial aneurysms.

Conclusions:

In a case-control study of patients with mirror location intracranial aneurysms, size ratio was identified as the unique morphological factor associate with the rupture of cerebral aneurysms.