bluuebunny/crossref_metadata_2025 huggingface dataset:
The Metabolic Epicenter of Supratentorial Gliomas: A1H-MRSI Study
Authors: Sankar Tejas , Kuznetsov Yevgeniy E. , Ryan Robert W. , Caramanos Zografos , Antel Samson B. , Arnold Douglas L. , Preul Mark C.
Published: December 2014

Background:

Assessing the impact of glioma location on prognosis remains elusive. We approached the problem using multivoxel proton magnetic resonance spectroscopic imaging (1H-MRSI) to define a tumor “metabolic epicenter”, and examined the relationship of metabolic epicenter location to survival and histopathological grade.

Methods:

We studied 54 consecutive patients with a supratentorial glioma (astrocytoma or oligodendroglioma, WHO grades II-IV). The metabolic epicenter in each tumor was defined as the1H-MRSI voxel containing maximum intra-tumoral choline on preoperative imaging. Tumor location was considered the X-Y-Z coordinate position, in a standardized stereotactic space, of the metabolic epicenter. Correlation between epicenter location and survival or grade was assessed.

Results:

Metabolic epicenter location correlated significantly with patient survival for all tumors (r2= 0.30, p = 0.0002) and astrocytomas alone (r2= 0.32, p = 0.005). A predictive model based on both metabolic epicenter location and histopathological grade accounted for 70% of the variability in survival, substantially improving on histology alone to predict survival. Location also correlated significantly with grade (r2= 0.25, p = 0.001): higher grade tumors had a metabolic epicenter closer to the midpoint of the brain.

Conclusions:

The concept of the metabolic epicenter eliminates several problems related to existing methods of classifying glioma location. The location of the metabolic epicenter is strongly correlated with overall survival and histopathological grade, suggesting that it reflects biological factors underlying glioma growth and malignant dedifferentiation. These findings may be clinically relevant to predicting patterns of local glioma recurrence, and in planning resective surgery or radiotherapy.
Cost-Effectiveness: Cholinesterase Inhibitors and Memantine in Vascular Dementia
Authors: Wong Camilla L. , Bansback Nick , Lee Philip E. , Anis Aslam H.
Published: December 2014

Background:

Several randomized controlled trials of cholinesterase inhibitors and memantine in mild to moderate vascular dementia have demonstrated the efficacy of these treatments. However, given these drugs incur considerable cost, the economic argument for their use is less clear.

Objective:

To determine the incremental cost-effectiveness of cholinesterase inhibitors and memantine for mild to moderate vascular dementia.

Design:

A decision analysis model using a 24-28 week time horizon was developed. Outcomes of cholinesterase inhibitors and memantine and probabilities of adverse events were extracted from a systematic review. Costs of adverse events, medications, and physician visits were obtained from local estimates. Robustness was tested with probabilistic sensitivity analysis using a Monte Carlo simulation.

Interventions:

Donepezil 5 mg daily, donepezil 10 mg daily, galantamine 16-24 mg daily, rivastigmine flexible dosing up to 6 mg twice daily, or memantine 10 mg twice daily versus standard care.

Main Outcome Measures:

Incremental cost-effectiveness ratio (ICER) expressed as cost per unit decrease in the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) subscale.

Results:

Donepezil 10 mg daily was found to be the most cost-effective treatment with an ICER of $400.64 (95%CI, $281.10-$596.35) per unit decline in the ADAS-cog subscale. All other treatments were dominated by donepezil 10 mg, that is, more costly and less effective.

Conclusion:

From a societal perspective, treatment with cholinesterase inhibitors or memantine was more effective but also more costly than standard care for mild to moderate vascular dementia. The donepezil 10 mg strategy was the most cost-effective and also dominated the other alternatives.
A Rare Case of Cerebral Cortical Dysplasia with Arterial Vascular Dysplasia
Authors: Shankar Jai Jai Shiva , Banerjee Susitna Trina , Hogan Matthew , terBrugge Karel , Lasjaunias Pierre , dos Santos Marlise P.
Published: December 2014

Background:

Cortical dysplasias are rarely associated with vascular anomalies. They are usually associated with venous anomalies or in few cases with both arterial and venous anomalies.

Methods:

Twenty-six year old female presented with history of headache showed cortical dysplasia associated with pure arterial dysplasia in the absence of any associated venous anomaly.

Conclusions:

An abnormal arterial supply to or an abnormal venous drainage from the growing cortex may result in cortical rearrangements that eventually give rise to various neuronal migration anomalies.
Sequestered Intradural Lumbar Disc
Authors: Mitha Alim P. , Hsu Forrest D. , Scott James N. , Addas Bassam M. , Starreveld Yves
Published: December 2014

A 42-year-old farmer was lifting a hay bale and experienced a sudden onset of sharp pain radiating down his left leg. Over the ensuing week, the pain became less pronounced, but was replaced with a progressive left greater than right leg numbness, foot weakness, and urinary hesitancy. He presented to his local hospital, where he was initially managed conservatively, and then transferred to our institution for consultation after an MR lumbar spine was completed. On physical exam, he had grade 1/5 weakness of left and right dorsi- and plantar flexion. Sensory testing showed a moderate decrease in pinprick sensation in his left leg from L1 to S1 dermatomes. He was symmetrically hyporeflexic with grade 1 knee reflexes and absent ankle jerks. Peri-anal sensation was intact, but there was moderately reduced rectal tone. The remainder of his neurological exam was normal.
Extracranial Carotid and Vertebral Artery Dissection: A Review
Authors: Redekop Gary John
Published: December 2014

Dissection of the extracranial carotid and vertebral arteries is increasingly recognized as a cause of transient ischemic attacks and stroke. The annual incidence of spontaneous carotid artery dissection is 2.5 to 3 per 100,000, while the annual incidence of spontaneous vertebral artery dissection is 1 to 1.5 per 100,000. Traumatic dissection occurs in approximately 1% of all patients with blunt injury mechanisms, and is frequently initially unrecognized. Overall, dissections are estimated to account for only 2% of all ischemic strokes, but they are an important factor in the young, and account for approximately 20% of strokes in patients less than 45 years of age. Arterial dissection can cause ischemic stroke either by thromboemboli forming at the site of injury or as a result of hemodynamic insufficiency due to severe stenosis or occlusion. Available evidence strongly favors embolism as the most common cause. Both anticoagulation and antiplatelet agents have been advocated as treatment methods, but there is limited evidence on which to base these recommendations. A Cochrane review on the topic of antithrombotic drugs for carotid dissection did not identify any randomized trials, and did not find that anticoagulants were superior to antiplatelet agents for the primary outcomes of death and disability. Healing of arterial dissections occurs within three to six months, with resolution of stenosis seen in 90%, and recanalization of occlusions in as many as 50%. Dissecting aneurysms resolve on follow-up imaging in 5- 40%, decrease in size in 15-30%, and remain unchanged in 50-65%. Resolution is more common in vertebral dissections than in carotid dissections. Aneurysm enlargement occurs rarely. The uncommon patient presenting with acute hemodynamic insufficiency should be managed with measures to increase cerebral blood flow, and in this setting emergency stent placement to restore cerebral perfusion may be considered, provided that irreversible infarction has not already occurred.
Motor Unit Number Estimation in Neuromuscular Disease
Authors: Rashidipour Omid , Chan K. Ming
Published: December 2014

Motor unit number estimation (MUNE) is an electrophysiological method designed to quantify motor unit loss in target muscles of interest. Most of the techniques are noninvasive and are therefore well suited for longitudinal monitoring. In this brief review, we describe the more commonly used techniques and their applications in amyotrophic lateral sclerosis, poliomyelitis, spinal muscular atrophy and hereditary sensorimotor neuropathies. Findings in some of these studies offer important pathophysiological insights. Since conventional electrophysiologic methods are not sensible measures of motor neuronal loss, MUNE could play a potentially important role in the diagnosis, monitoring of disease progression and response to treatment in neuromuscular diseases in which motor unit loss is a major feature.
Effect of Ximelagatran and Warfarin on Stroke Subtypes in Atrial Fibrillation
Authors: Teitelbaum Jeanne S. , von Kummer Rüdiger , Gjesdal Knut , Kristinsson Arni , Gahn Georg , Albers Gregory W.
Published: December 2014

ABSTRACT

Background and Purpose:

The most common stroke subtype among atrial fibrillation (AF) patients not receiving anticoagulants is cardioembolic. In the SPORTIF III and V trials, the oral direct thrombin inhibitor ximelagatran was as effective as warfarin in reducing the risk of stroke in patients with nonvalvular AF. We assessed any differential effect of warfarin versus ximelagatran on the risk and outcome of cardioembolic and noncardioembolic stroke.

Methods:

7329 patients with AF and ≥1 risk factors for stroke were randomized to treatment with warfarin (target international normalized ratio 2.0-3.0) or fixed-dose ximelagatran. Strokes were classified into specific subtypes. Therapeutic effect of warfarin and ximelagatran, adverse events, and stroke outcomes were assessed according to stroke subtype.

Results:

The annual stroke rate was low for both cardioembolic (ximelagatran, 0.39%; warfarin, 0.47%) and noncardioembolic stroke (ximelagatran, 0.57%; warfarin, 0.37%). In ischemic strokes, 33.9% (ximelagatran) and 34.3% (warfarin) had strokes of presumed cardioembolic origin. When fatal stroke, disabling stroke, myocardial infarction, and death from any cause were combined as poor outcome, patients with cardioembolic strokes had the highest rate of poor outcome (40%) but this was non- significant.

Conclusions:

In SPORTIF III and V the efficacy of warfarin and ximelagatran were similar for prevention of cardioembolic and noncardioembolic strokes. Overall outcome tended to be worse following cardioembolic stroke. Ximelagatran has been withdrawn from the market due to hepatic side effects, but similar compounds are presently being studied.
Effect of Therapy on Motor Cortical Excitability in Parkinson’s Disease
Authors: Soysal Aysun , Sobe Ismail , Atay Turan , Sen Aysu , Arpaci Baki
Published: December 2014

Objective:

To assess the impact of the disease stage and therapy on motor cortical excitability in Parkinson’s disease (PD).

Methods:

Twenty newly diagnosed and medication-free, early stage patients, 20 late stage patients under antiparkinsonian therapy and 20 normal healthy controls were included. Motor threshold (MT), amplitudes of motor evoked potential (MEP), motor evoked potential amplitude/compound muscle action potential amplitude (MEP/CMAP) ratio, central motor conduction time (CMCT) and cortical silent period (CSP) were measured by stimulation of the motor cortex using a 13.5 cm circular coil and recordings from abductor digiti minimi muscle. Following the first study protocol, early stage patients were given therapy and the same protocol was repeated three months later.

Results:

Motor threshold was lower; and the MEP/CMAP ratio was higher in early and late stage patients than normals. In early stage patients after proper therapy, the MTs became higher than before therapy, but still remained lower than normals. In late stage patients, the CMCTs were shorter than the early stage patients before therapy and normals, but there was no difference between the early stage patients and normals. In early stage patients after therapy, the CMCT became longer than before therapy and this difference was significant in both late stage patients and normals. Although more prominent in late stage patients, the CSP duration in both PD groups was found shorter than normals. In early stage patients, after therapy, the CSP durations became significantly longer compared with before therapy.

Conclusion:

These findings suggest that the motor cortical excitability increases in PD because of the impairment of the corticomotoneuronal inhibitory system.
Pergolide Associated Cardiac Valvulopathy Based on Ontario Administrative Data
Authors: Zadikoff Cindy , Duong-Hua Minh , Sykora Kathy , Marras Connie , Lang Anthony , Rochon Paula
Published: December 2014

Introduction:

Pergolide is an ergot derived dopamine agonist that is widely used for the treatment of Parkinson’s disease. Studies have found an association between pergolide and valvular heart abnormalities although there is still much to be learned about the clinical significance of the valvular changes, who is at risk, and whether there is duration of exposure effect.

Objective:

To assess the long term risk of hospital admissions for valvular heart disease (VHD) or congestive heart failure (CHF, a clinically overt outcome of VHD) in new users of pergolide compared to new users of levodopa. The secondary objective was to assess whether there are any characteristics that can predict who is at higher risk of developing this outcome.

Design:

Retrospective, population-based cohort study.

Setting:

Ontario, Canada.

Subjects:

Ontario residents aged 66 and older, newly started on treatment with either pergolide or levodopa.

Outcomes:

Admission to hospital with the most responsible diagnosis of congestive heart failure or valvular heart disease.

Results:

The risk for admission for valvular heart disease or congestive heart failure were higher in those with 1-4 years exposure to pergolide compared with no exposure to pergolide (VHD: hazard ratio 2.4, p = 0.04; CHF: hazard ratio 1.6, p =0.02). No such pattern was found with exposure to levodopa.

Conclusion:

Our study demonstrates that treatment with pergolide is associated with a higher risk of hospital admission for valvular heart disease or congestive heart failure and that this risk is greater in those with 1-4 years exposure than in those with less exposure. We did not find an increased risk beyond four years.
When Temozolomide Alone Fails: Adding Procarbazine in Salvage Therapy of Glioma
Authors: Huang Fleur , Kavan Petr , Guiot Marie-Christine , Markovic Yelena , Roberge David
Published: December 2014

Background:

Since temozolomide (TMZ) entry into routine practice in the first-line management of glial tumors, post-TMZ recurrences present a growing challenge. Without standard chemotherapy for TMZ failure, care in such palliative settings requires consideration not only of efficacy but of toxicity and convenience.

Methods:

At our institution, a combination regimen has been used: oral alkylating agents procarbazine (PCB) (100-150 mg/m2/day) and TMZ (150-200 mg/m2/day) administered on days 1-5 of a 28-day cycle. This treatment has been initiated upon radiological and/or clinical disease progression, and continued until evidence of further progression or toxicity. We retrospectively reviewed our experence with this regimen.

Results:

Since November 2004, 17 patients (median age 53) were treated for histologically confirmed glioma (glioblastoma multiforme (GBM), N=12; Grade 3 glioma, N=3; Grade 2 glioma, N=2) after a median of 2 recurrences. TMZ was previously given either as adjuvant therapy (post-chemoradiotherapy maintenance in 8 of 13 cases) or as salvage monotherapy (4 cases). Of 16 evaluable cases, 14 (13 high grade tumors) showed O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. Two patients achieved partial response and one had complete response by RECIST criteria. Disease progressed after a median of 4 cycles (range 1 to 11+), with an actuarial progression-free survival of 42% after 6 cycles. Grade 3/4 toxicity was rare, and no dose reductions were needed. One patient discontinued treatment due to procarbazine hypersensitivity.

Conclusion:

Combination PCB-TMZ is well-tolerated, with modest activity in TMZ-exposed glioma.
Pituitary Adenomas: Presentations and Outcomes in a South Asian Country
Authors: Shamim Muhammad Shahzad , Bari Muhammad Ehsan , Khursheed Faraz , Jooma Rashid , Enam Syed Ather
Published: December 2014

Objective:

: The purpose of this retrospective review of all operated cases of pituitary adenomas in the last decade, is to define the demographic patterns and characteristics of such tumors and to assess surgical outcomes with regards to safety and efficacy of trans–sphenoidal tumor removal in our institution.

Methods:

Surgically treated pituitary adenomas presenting from 1995 till 2005 were reviewed for different variables. Results were expressed as mean, standard deviation and median for continuous and number with percentage for categorical data. Chi square test was applied to measure differences and significance was taken at p value < 0.05.

Results:

One hundred and twenty–five patients were operated for pituitary adenoma. Sixty–three percent were male and mean age was 37 years. Sixty percent of the patients presented with headache and/or visual symptoms. Twelve percent presented with pituitary apoplexy and 28% presented with symptoms due to pituitary hyperfunction. Fifty–five percent of patients had functioning and 44% had nonfunctioning adenomas. Mean pre operative tumor diameter from 86 pre op MRI scans was 26.76 mm (3–78 mm). Eighty–four percent of patients underwent trans–sphenoidal tumor resection and three percent had craniotomy. Mean size of post op residual tumor as calculated from 76 available post operative scans was 5.3 mm (range 0–31 mm). 17.6% of the patients required hormone replacement beyond three months and 10% were re–operated. Overall mortality was 1.6%.

Conclusion:

In Pakistan, patients are more likely to present either with apoplexy or with a giant pituitary adenoma than patients reported from developed countries. Overall, our results have been satisfactory and comparable with the literature.
Leptomeningeal Disease from Oligodendroglioma: Clinical and Molecular Analysis
Authors: Roldán Gloria , Scott James , George David , Parney Ian , Easaw Jacob , Cairncross Gregory , Forsyth Peter , Yan Elizabeth
Published: December 2014

Background:

Leptomeningeal disease (LMD) is a late complication of malignant glioma, mostly of glioblastoma, that usually responds poorly to treatment and is rapidly fatal. A long surviving case led us to review our experience with LMD in patients with oligodendrogliomas.

Methods:

A 15-year retrospective chart review was performed. Patients with both oligodendroglial tumors and LMD were identified. A single neuro-pathologist reviewed all histological sections, a single neuro-radiologist reviewed all available images and lp/19q status was assessed.

Results:

Seven out of 145 patients with oligodendroglioma were diagnosed with LMD. Six were male. Median age at tumor diagnosis was 41 years (range, 28-50). None had radiographic or pathological evidence of leptomeningeal or subependymal tumor at initial diagnosis. Most patients had pure anaplastic oligodendrogliomas (4/7); 6/7 had 1p/19q co-deletion. The median time to first relapse was 41 months (range, 19-127). The median time to LMD was 76 months (range, 19-151) from initial diagnosis and 28 months (range, 0-36) from first relapse, respectively. Leptomeningeal disease treatments included spinal radiation and intrathecal and systemic chemotherapy. After progression, some patients with LMD remained stable clinically. The median survival from initial diagnosis was 104 months (range, 19-183) and from LMD diagnosis was 32 months (range, 2-43).

Conclusion:

Leptomeningeal disease is a complication of oligodendroglioma that may occur preferentially in long surviving patients with 1p/19q co-deletion. Leptomeningeal disease in patients with oligodendrogliomas appears to be relatively indolent which may have implications for their treatment and be related to 1p/19q status.
Effect of ALS IgG on Motor Neurons in Organotypic Spinal Cord Cultures
Authors: Li Bin , Liu Xiao-Yun , Li Zhe , Bu Hui , Sun Meng-Meng , Guo Yan-Su , Li Chun-Yan
Published: December 2014

Objective:

Reports about the role of autoimmunity in amyotrophic lateral sclerosis (ALS) are inconsistent. The aim of this work was to investigate the effect of IgG from patients with ALS on motor neurons in a physiological-like surrounding.

Methods:

Using affinity chromatography, IgG from six ALS patients, four disease controls and five healthy subjects was purified. Organotypic spinal cord cultures, which conserve the structure of the spinal cord in a horizontal plane and are suitable for studies with long-term treatment, were used and IgG with different concentrations ranging from 0.05 mg/mL to 0.5 mg/mL was added to the culture medium. Ventral motor neuron survival was evaluated by morphology and SMI-32 immunohistochemistry staining. Lactate dehydrogenase (LDH) level in the culture medium was measured by colorimetry.

Results:

After cultures were treated with ALS IgG for three weeks, the number and morphology of motor neurons showed little change. In addition, there was no significant difference in lactate dehydrogenase release between cultures treated with medium alone, normal control IgG, disease control IgG or ALS IgG.

Conclusions:

The results indicate that IgG from these ALS patients was insufficient per se to induce motor neuron death in Organotypic slice cultures. However, this does not preclude the possibility that other changes may have occurred in the motor neurons. This work offered a new model to evaluate the role of IgG in the pathogenesis of ALS. Organotypic cultures contribute to study of the impact of IgG on motor neurons by mimicking physiological conditions.
The Role of Piriform Cortex Adenosine A1 Receptors on Hippocampal Kindling
Authors: Namvar Simin , Mirnajafi-Zadeh Javad , Fathollahi Yaghoub , Zeraati Maryam
Published: December 2014

Introduction:

The hippocampus and piriform cortex have a critical role in seizure propagation. In this study, the role of adenosine A1 receptors of piriform cortex on CA1 hippocampal kindled seizures was studied in rats.

Methods:

Animals were implanted with a tripolar electrode in the right hippocampal CA1 region and two guide cannulae in the left and right piriform cortex. They were kindled by daily electrical stimulation of hippocampus. In fully kindled rats, N6- cyclohexyladenosine (CHA; a selective adenosine A1 receptors agonist) and 1, 3-dimethyl-8-cyclopenthylxanthine (CPT a selective adenosine A1 receptor antagonist) were microinfused into the piriform cortex. The animals were stimulated at 5, 15 and 90 minutes (min) after drag injection.

Results:

Obtained data showed that CHA (10 and 100 μM) reduced afterdischarge duration, stage 5 seizure duration, and total seizure duration at 5 and 15 min after drag injection. There was no significant change in latency to stage 4 seizure. CPT at concentration of 20 μM increased afterdischarge duration, stage 5 seizure duration, and total seizure duration and decreased latency to stage 4 seizure at 5 and 15 min post injection. Pretreatment of rats with CPT (10 μM), 5 min before CHA (100 μM), reduced the effect of CHA on seizure parameters.

Conclusion:

These results suggested that activity of adenosine A1 receptors in the piriform cortex has an anticonvulsant effect on kindled seizures resulting from electrical stimulation of the CA1 region of the hippocampus.
The Return of Evidence-Based Neurology to the Journal: It’s All About Patient Care
Authors: Jenkins ME , Burneo JG
Published: December 2014

Finding the current best evidence for care of the neurological patient and keeping up-to-date with new advances in clinical research is challenging. New medical knowledge is evolving quickly, but most studies lead nowhere or are too preliminary to act on and serve to bury or at least camouflage the few important studies. Evidence Based Clinical Practice (EBCP) is becoming an important and vital tool in this rapidly changing culture. As the quantity of neurological research publications continues to expand exponentially, evidence based principles provide a systematic and comprehensive strategy to approach this literature. There is a need for more availability of evidence based critically appraised information in the clinical neurosciences.
Seizure Freedom Reduces Illness Intrusiveness and Improves Quality of Life in Epilepsy
Authors: Poochikian-Sarkissian Sonia , Sidani Souraya , Wennberg Richard , Devins Gerald M.
Published: December 2014

Background:

Chronic illnesses are associated with multiple stressors that compromise quality of life (QOL). Implicit in many of these stressors is the concept of illness intrusiveness: the disruption of lifestyles, activities, and interests due to the constraints imposed by chronic disease and its treatment. The purpose of this study was to examine illness intrusiveness and QOL in epilepsy in patients with different levels of seizure control.

Methods:

Cross-sectional data were obtained and compared between two groups of patients categorized by presence of seizures: seizure freedom or continued seizures (N=145). Standard instruments measured the following variables: illness intrusiveness, perceived personal control, subjective well-being, and disease specific QOL.

Results:

Illness intrusiveness varied inversely and significantly with seizure control. Complete seizure freedom, whether achieved by pharmacological or surgical treatment, was associated with the lowest levels of illness intrusiveness. Seizure freedom was also associated with increased perceived control, positive affect, self-esteem and QOL in epilepsy.

Conclusions:

The most robust benefits of decreased illness intrusiveness in epilepsy occur when treatment leads to complete seizure control. Therefore every effort should be made by health care providers to achieve seizure freedom to reduce illness intrusiveness and improve QOL in epilepsy.
The Prevalence of Cerebral Palsy in British Columbia, 1991-1995
Authors: Smith Les , Kelly Karen D. , Prkachin Glenda , Voaklander Donald C.
Published: December 2014

Objective:

To quantify the prevalence of cerebral palsy (CP) in British Columbia within a four-year birth cohort.

Methods:

The study was a population-based record linkage study of a birth cohort of British Columbian children born between April 1, 1991 and March 31, 1995. Cases were identified by the presence of International Classification of Diseases, Version 9 (ICD-9) diagnostic code “343” recorded at three years of age or older or by having the ICD-9 diagnostic code “343” recorded prior to the third birthday with two confirmatory diagnoses within the first three years of life through a record search of the BC Medical Services Plan billing files for the fiscal years 1991 to 1995.

Results/Conclusion:

This research has provided an estimate of the prevalence of CP in the four-year birth cohort 1991 to 1995 in British Columbia. An aggregate prevalence rate of CP was measured as 2.68 per 1000 live births, and a congenital rate was measured at 2.57 for the same population. Birth weight and gestational age demonstrated a significant relationship with the development of CP. This study should lend credence to the establishment of a CP register in British Columbia.
Internal Carotid Artery Septa in Sickle Cell Disease: Risk Factor for Stroke?
Authors: Sharma Pranshu , Goyal Mayank , Al-Khathaami Ali M. , Demchuk Andrew
Published: December 2014

Sickle cell disease is a hemoglobinopathy occurring due to replacement of valine for glutamic acid at the sixth position of the beta globin chain. The altered hemoglobin structure makes it prone for polymerization during hypoxic and infective stress. Polymerization of the hemoglobin molecule leads to sickling of the red blood cells in the vessels causing thrombosisvasoocclusive crises. Although abdomen and extremities are more often involved, silent cerebral infarcts and stroke can occur in up to 25-29% of patients and is the major cause of morbidity and mortality.
Insulin Resistance and High Sensitivity C-Reactive Protein in Migraine
Authors: Guldiken Baburhan , Guldiken Sibel , Demir Muzaffer , Turgut Nilda , Kabayel Levent , Ozkan Hulya , Ozcelik Emine , Tugrul Armagan
Published: December 2014

Background:

A relationship between migraine and vascular disorders such as hypertension, stroke, and coronary ischemia has been recently reported. Insulin resistance and endothelial dysfunction, which commonly underlies these disorders, have not been widely investigated in migraine patients. In this study, we aimed to investigate the existence of insulin resistance and endothelial dysfunction, and their relationship to vascular risk factors in patients with migraine.

Methods:

We evaluated insulin resistance and high-sensitivity C-reactive protein (hs-CRP), a marker of endothelial dysfunction, in 60 migraine patients and 25 healthy control subjects. Multiple analysis of covariance test was used to adjust for known confounding factors that can influence insulin metabolism and endothelial function, such as obesity, blood pressure, and lipid parameters.

Results:

Insulin resistance, as measured homeostasis model assessment (HOMA)-R levels, was significantly higher in the migraine group (p<0.001). After adjustment for confounding variables, the relationship between migraine and the HOMA-R levels remained significant (p<0.001). The hs-CRP levels did not differ between the migraine and control groups.

Conclusions:

Our data show that insulin resistance is present in migraine patients. Endothelial dysfunction is not found during the headache-free period. Further studies are needed to explain the role of insulin resistance in migraine pathogenesis.
Effects of Rivastigmine on Memory and Cognition in Multiple Sclerosis
Authors: Shaygannejad Vahid , Janghorbani Mohsen , Ashtari Fereshteh , Zanjani Hamid Afshar , Zakizade Naser
Published: December 2014

Background:

Cognitive dysfunction is one of the common clinical symptoms in multiple sclerosis (MS), but there is no effective treatment for it.

Objective:

The aim of this study was to evaluate the effect of rivastigmine in treating memory and cognitive dysfunction in MS.

Methods:

A single-center double-blind placebo-controlled randomized clinical trial conducted from October 2005 to February 2007. Sixty definite MS patients with cognitive impairment age 16 to 54 years were randomly allocated to receive a 12-week treatment course of either rivastigmine (1.5 mg once a day increment over 4 weeks to 3 mg twice daily) or placebo. Response to treatment was assessed by the Wechsler Memory Scale (WMS) at baseline and 12 weeks after start of therapy.

Results:

A slight, but significant memory improvement occurred in both groups. Of the 30 patients treated with rivastigmine, the mean (SD) WMS general memory score increased from 60.3 (4.2) at baseline to 64.9 (5.3) at the end of study period (P<0.001). Correspondingly, in the 30 patients treated with placebo, the mean (SD) WMS general memory score increased from 60.5 (4.9) to 64.5 (3.7) (P < 0.001). The average WMS general memory score at the end of trial did not changed between rivastigmine and placebo group (mean difference, 0.4; 95% CI, -2.0, 2.8).

Conclusion:

No significant differences were seen between rivastigmine and placebo on the mean (SD) WMS general memory score. A larger multicenter study of rivastigmine in MS is warranted in order to more definitely assess the efficacy of this intervention.
Retinal Nerve Fiber Layer and Future Risk of Multiple Sclerosis
Authors: Costello Fiona , Hodge William , Pan Y. Irene , Metz Luanne , Kardon Randy H.
Published: December 2014

Background:

Optical coherence tomography (OCT) - measured retinal nerve fiber layer (RNFL) values may represent a surrogate biomarker for axonal integrity in multiple sclerosis (MS). The purpose of this study was to determine whether RNFL measurements obtained within two years of an optic neuritis (ON) event distinguish patients at increased risk of developing clinically-definite MS (CDMS).

Methods:

Fifty consecutively sampled patients who experienced a single ON event were followed prospectively for a mean period of 34 months with OCT testing. Values of RNFL in clinically-affected and non-affected eyes were compared between patients who developed CDMS and those that did not develop MS after ON.

Findings:

Twenty-one patients (42%) developed CDMS during the course of the study, with a mean conversion time of 27 months. Mean RNFL values were thinner in the clinically - affected eyes of non - MS patients than CDMS eyes after one year (p = 0.0462) due to more severe ON events in the former. By year two, CDMS patients manifested more recurrent ON events and RNFL thinning than non - MS patients. Temporal RNFL values were thinner in the non-affected eyes of CDMS patients with a trend towards significance (p = 0.1302).

Interpretation:

Our results indicate that RNFL thickness does not reliably distinguish patients at higher risk of converting to CDMS after ON. The severity of ON has a greater effect on RNFL thickness than risk of CDMS at one year. The CDMS patients demonstrate progressive RNFL thinning likely due to recurrent sub-clinical ON events, which may help differentiate them from non - MS patients over time.
Spinocerebellar Ataxia Type 12 was not Found in Korean Parkinsonian Patients
Authors: Cho Jin Whan , Kim Sung Yeon , Park Sung Sup , Jeon Beom S.
Published: December 2014

Background:

Parkinsonism (PD) is occasionally seen in several types of spinocerebellar ataxia (SCA). Mutations in SCA gene have been reported in the patients of parkinsonism without ataxia.

Methods:

We examined spinocerebellar ataxia type 12 mutation in 877 PD and 199 multiple system atrophy (MSA) patients.

Results and Conclusions:

No patients showed abnormal SCA12 expansion. It suggests that PD and MSA are not associated with SCA12 and it is not necessary to screen SCA12 in PD and MSA patients.
The Vestibulo-ocular Reflex During Active Head Motion in Chiari II Malformation
Authors: Salman Michael S. , Sharpe James A. , Lillakas Linda , Dennis Maureen , Steinbach Martin J.
Published: December 2014

Background:

Chiari type II malformation (CII) is a developmental anomaly of the cerebellum and brainstem, which are important structures for processing the vestibulo-ocular reflex (VOR). We investigated the effects of the deformity of CII on the angular VOR during active head motion.

Methods:

Eye and head movements were recorded using an infrared eye tracker and magnetic head tracker in 20 participants with CII [11 males, age range 8-19 years, mean (SD) 14.4 (3.2) years]. Thirty-eight age-matched healthy children and adolescents (21 males) constituted the control group. Participants were instructed to ‘look’ in darkness at the position of their thumb, placed 25 cm away, while they made horizontal and vertical sinusoidal head rotations at frequencies of about 0.5 Hz and 2 Hz. Parametric and non-parametric tests were used to compare the two groups.

Results:

The VOR gains, the ratio of eye to head velocities, were abnormally low in two participants with CII and abnormally high in one participant with CII.

Conclusion:

The majority of participants with CII had normal VOR performance in this investigation. However, the deformity of CII can impair the active angular VOR in some patients with CII. Low gain is attributed to brainstem damage and high gain to cerebellar dysfunction.
Peripheral Sensory Axon Growth: From Receptor Binding to Cellular Signaling
Authors: Tucker Budd A. , Mearow Karen M.
Published: December 2014

Regeneration following axonal injury of the adult peripheral sensory nervous system is heavily influenced by factors located in a neuron's extracellular environment. These factors include neurotrophins, such as Nerve Growth Factor (NGF) and the extracellular matrix, such as laminin. The presence of these molecules in the peripheral nervous system (PNS) is a major contributing factor for the dichotomy between regenerative capacities of central vs. peripheral neurons. Although PNS neurons are capable of spontaneous regeneration, this response is critically dependent on many different factors including the type, location and severity of the injury. In this article, we will focus on the plasticity of adult dorsal root ganglion (DRG) sensory neurons and how trophic factors and the extracellular environment stimulate the activation of intracellular signaling cascades that promote axonal growth in adult dorsal root ganglion neurons.
Intraspinal Neurenteric Cysts in Children
Authors: Cai Chunquan , Shen Changhong , Yang Weidong , Zhang Qingjiang , Hu Xiaoli
Published: December 2014

Background:

Neurenteric cysts are rare congenital epithelium-lined cysts of the central nervous system. They are found predominantly in the spinal cord, with lower incidence in the intracranial compartment, and may be associated with various other congenital spinal anomalies. Seven patients with symptomatic intraspinal neurenteric cysts are presented.

Materials and Methods:

Seven patients with intraspinal neurenteric cysts aged from nine months to ten years treated at this hospital from May 2000 to July 2006 were reviewed. The clinical manifestations, imaging and surgical findings of patients were analyzed retrospectively. All patients underwent operation. One patient's cervical neurenteric cyst was resected using the lateral cervical approach, and the other six resections were performed with posterior approach.

Results:

All seven patients presented with neurological involvement. One patient had an intramedullary cyst, while the other six cysts were situated ventrally. Three patients' cysts occurred in the cervical region, two in the cervicothoracic region, one in the thoracic region and one in the lumbar region. One patient had bony anomalies, and one had a lumbar posterior occult spinal dysraphism. Five patients' symptoms improved rapidly after surgery.

Conclusions:

Intraspinal neurenteric cysts in children are rare and most occur ventral to the spinal cord. Magnetic resonance imaging (MRI) is the most effective imaging modality. Earlier diagnosis and surgical resection of spinal neurenteric cysts improves prognosis.
Circulating Endothelial Cells as Potential Markers of Atherosclerosis
Authors: Gao Yang , Liu Chunyan , Zhang Xiangjian , Gao Jian , Yang Chunyan
Published: December 2014

Background and Purpose:

Vascular endothelial cell (VEC) injury represents a major initiating step in the process of atherosclerosis, which may lead to cerebral infarction. “Circulating endothelial cell” (CEC) is an index of ongoing endothelial injury, while intimal-medial thickness (IMT) detected by sounography was used to evaluate the severity of atherosclerosis. However, to our knowledge, there is no study that investigated the relationship of these two determinations. Our study was designed to address correlate CEC with IMT.

Methods and Results:

The study population consisted of 30 patients with acute cerebral infarction (ACI) and 30 age-and sex-matched volunteers as controls. The CEC counts were determined using Hladovec's method. All subjects underwent a 2-dimensional ultrasound examination of both carotid arteries to measure IMT. CEC counts in ACI group were significantly increased compared with control group (4.88±2.14 cells /0.9μl vs 2.73±1.95/0.9μl, P0.01); IMT in ACI patients was also significantly thicker compared with volunteers (2.72±1.07 mm vs 1.73±0.99 mm, P<0.01). There was positive correlation between CEC counts and maximal carotid artery IMT in both groups (r=0.522, P<0.01 in ACI patients and r=0.395, P<0.05 in healthy volunteers).

Conclusions:

Circulating endothelial cell counts can directly reflect the vascular injury. CEC counts parallel IMT. The CEC may be an independent predictor of cerebral infarction.
Peripheral Trauma Induced Dystonia or Post-Traumatic Syndrome?
Authors: Kumar Hrishikesh , Jog Mandar
Published: December 2014

The relationship between peripheral trauma and dystonia has been debated for more than a century but the issue still remains controversial. There are passionate supporters and detractors of the association and both the groups have their own arguments. This review aims to critically evaluate those arguments and presents current understanding of this association. In the process, the relevant case series and scientific papers exploring this subject have been discussed. Upon careful review of available literature coupled with their own experience, the authors believe that peripheral trauma can predispose to abnormal posturing of a body part after variable intervals. To call this posturing a “post-traumatic dystonia” might be premature and the term “post-traumatic syndrome” can be used instead. More work is needed to unravel the pathophysiology of this post-traumatic syndrome.
Multisystem Disorder in Late-Onset Chronic Progressive External Ophthalmoplegia
Authors: Pfeffer Gerald , Sirrs Sandra , Wade N. Kevin , Mezei Michelle M.
Published: December 2014

Introduction:

Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial syndrome on a disease spectrum with Kearns-Sayre syndrome (KSS). Clinical presentation is variable and our experience suggested that phenotypic differences exist in CPEO with onset after age 20.

Methods:

This descriptive study is a retrospective chart review of 40 patients with late-onset CPEO. Clinical features, laboratory and neurophysiology results were reviewed.

Results:

Multisystem dysfunction was very common in this series. Gastrointestinal dysfunction was more common than expected (60%) as was migraine headache (40%). Clinical characteristics on the KSS disease spectrum were uncommon in this series with only 2.5% having pigmentary retinopathy, 5% with cardiac conduction abnormality, and 22.5% having endocrinopathy (most often thyroid dysfunction rather than diabetes). Neurophysiology abnormalities included length-dependent axonal polyneuropathy in 44% (sometimes subclinical) and myopathic EMG changes in 26%. Exposure to sources of acquired mitochondrial toxicity including cigarette use and hepatitis C infection were more common than expected in this series.

Discussion:

Phenotype was different in this late-onset series compared with previous reports in CPEO patients. In this series of late-onset patients, multi-organ dysfunction was more common than previously reported in CPEO, and some classical mitochondrial manifestations, such as pigmentary retinopathy were rare. We suggest that acquired mitochondrial toxicity may have a role in the pathogenesis of adult-onset CPEO.
Effect of Lentiviral shRNA of Nogo Receptor on Rat Cortex Neuron Axon Outgrowth
Authors: Xu Shengming , Liu Mingyuan , Zhang Tao , Lv Bitao , Liu Baifeng , Yuan Wen
Published: December 2014

Background and Aims:

Axon growth is crucial for injured neural tissue to recover; however it is difficult to achieve in general. Axon outgrowth is inhibited by the activation of the Nogo receptor (NgR) by one of three different ligands. The present study aimed to suppress the inhibitory effect of the three inhibitory proteins to facilitate axon outgrowth.

Methods:

A lentiviral vector, siNgR199 (that has the capacity to interfere with the gene of NgR expression), was constructed for suppressing the gene transcription of NgR. Rat cortex neurons and oligodendrocytes were prepared to observe the effect of siNgR199 on facilitating axon outgrowth.

Results:

After transfection, the lentiviral siRNA of NgR remained in target neurons for almost two weeks whereas the conventional siRNA of NgR remained in neurons less than five days. Lentivirus-mediated delivery of exogenous small interfering RNA (siNgR199) targeting NgR significantly reduced the expression of this receptor and promoted axon outgrowth. In contrast, provision of naked siRNA targeting NgR (NgRsiRNA) showed less inhibitory effect on NgR protein expression and did not affect axon outgrowth.

Conclusions:

Lentiviral siRNA of NgR effectively suppresses the expression of NgR in cultured neurons that facilitates the axon outgrowth. The data implicate that lentiviral siRNA of NgR has therapeutic potential in facilitating the recovery of injured neural tissue.
Blood Pressure and Early Clinical Outcome Among Acute Ischemic Stroke Patients
Authors: Zhang Jintao , Peng Ying , Fan Huanqing , Chen Mei , Xu Tan , Zhang Yonghong
Published: December 2014

Objectives:

The association between blood pressure (BP) and short-term clinical outcome of acute ischemic stroke is inconclusive. We investigated the association between BP in the first 72 hours following admission and death in-hospital and neurologic deficiency at discharge among patients with acute ischemic stroke.

Methods:

A total of 2675 acute ischemic stroke patients confirmed by a computed tomography scan or magnetic resonance imaging were included in the present study. Blood pressure in the first 72 hours after admission and other study variables were collected for all ischemic stroke patients. Neurological functions National Institute of Health Stroke Scale (NIHSS) were evaluated by trained neurologists at discharge. The study outcome was defined as death in-hospital and neurologic deficiency (NIHSS≥10) at discharge.

Results:

Systolic and diastolic BP were significantly and positively associated with odds of study outcome in acute ischemic stroke. For example, compared to those with a systolic BP<140 mmHg, multiple-adjusted odds ratio (95% confidence interval) of study outcome was 3.29(1.22, 8.90) among participants with systolic BP of 180-219 mmHg,P<0.05; compared to those with a diastolic BP<90 mmHg, multiple-adjusted odds ratio of study outcome was 7.05(1.32, 37.57) among participants with diastolic BP ≥ 120 mmHg,P<0.05.

Conclusion:

Systolic BP≥180 and diastolic BP≥120 were significantly and positively associated with death in-hospital or neurologic deficiency at discharge among patients with acute ischemic stroke.
Carotid Endarterectomy Versus Stenting: A Meta-Analysis of Randomized Trials
Authors: Yavin Daniel , Roberts Derek J. , Tso Michael , Sutherland Garnette R. , Eliasziw Misha , Wong John H.
Published: December 2014

Background:

A meta-analysis of randomized controlled trials (RCTs) was conducted to update the available evidence on the safety and efficacy of carotid endarterectomy (CEA) versus carotid artery stenting (CAS) in the treatment of carotid artery stenosis.

Methods:

A comprehensive search was performed of MEDLINE, EMBASE, CENTRAL, bibliographies of included articles and past systematic reviews, and abstract lists of recent scientific conferences. For each reported outcome, a Mantel-Haenszel random-effects model was used to calculate odds ratios (ORs) and 95% confidence intervals (CI). The I2statistic was used as a measure of heterogeneity.

Results:

Twelve RCTs enrolling 6,973 patients were included in the meta-analysis. Carotid artery stenting was associated with a significantly greater odds of periprocedural stroke (OR 1.72, 95% CI 1.20 to 2.47) and a significantly lower odds of periprocedural myocardial infarction (OR 0.47, 95% CI 0.29 to 0.78) and cranial neuropathy (OR 0.08, 95% CI, 0.04 to 0.16). The odds of periprocedural death (OR 1.11, 95% CI 0.56 to 2.18), target vessel restenosis (OR 1.95, 95% CI 0.63 to 6.06), and access-related hematoma were similar following either intervention (OR 0.60, 95% CI 0.30 to 1.21).

Conclusions:

In comparison with CEA, CAS is associated with a greater odds of stroke and a lower odds of myocardial infarction. While the results our meta-analysis support the continued use of CEA as the standard of care in the treatment of carotid artery stenosis, CAS is a viable alternative in patients at elevated risk of cardiac complications.