bluuebunny/crossref_metadata_2025 huggingface dataset:
Fetal vascular adaptation before and after treatment of severe maternal anemia in pregnancy
Authors: Ali Eram , Kumar Manisha , Naqvi Sayyed E.H. , Trivedi Shubha S. , Singh Anuradha
Published: February 2016

Objectives

To use color Doppler ultrasonography indices to study the effects on fetal circulation of treating severe maternal anemia.

Methods

A prospective cohort study enrolled patients who were at 30–34 weeks of pregnancy and had hemoglobin levels below 70 g/L between November 1, 2011 and March 31, 2013 at a hospital in New Delhi, India. A control group consisting of patients with the same duration of pregnancy and with hemoglobin levels above 110 g/L was included. Umbilical artery and middle cerebral artery velocimetry were performed using color Doppler ultrasonography at admission and after 4 weeks and 6 weeks of treatment.

Results

The maternal anemia cohort demonstrated a significantly lower middle cerebral artery resistance index and middle cerebral/umbilical artery resistance ratio (P < 0.001) at admission. Following 4 weeks of treatment for maternal anemia, significant increases in these parameters were observed (P < 0.001).

Conclusion

Fetuses of individuals with severe maternal anemia demonstrated altered cerebral and umbilical artery flows. Normal flows were restored following treatment of maternal anemia.
National and Regional Representativeness of Hospital Emergency Department Visit Data in the National Syndromic Surveillance Program, United States, 2014
Authors: Coates Ralph J. , Pérez Alejandro , Baer Atar , Zhou Hong , English Roseanne , Coletta Michael , Dey Achintya
Published: February 2016

Objective

We examined the representativeness of the nonfederal hospital emergency department (ED) visit data in the National Syndromic Surveillance Program (NSSP).

Methods

We used the 2012 American Hospital Association Annual Survey Database, other databases, and information from state and local health departments participating in the NSSP about which hospitals submitted data to the NSSP in October 2014. We compared ED visits for hospitals submitting data with all ED visits in all 50 states and Washington, DC.

Results

Approximately 60.4 million of 134.6 million ED visits nationwide (~45%) were reported to have been submitted to the NSSP. ED visits in 5 of 10 regions and the majority of the states were substantially underrepresented in the NSSP. The NSSP ED visits were similar to national ED visits in terms of many of the characteristics of hospitals and their service areas. However, visits in hospitals with the fewest annual ED visits, in rural trauma centers, and in hospitals serving populations with high percentages of Hispanics and Asians were underrepresented.

Conclusions

NSSP nonfederal hospital ED visit data were representative for many hospital characteristics and in some geographic areas but were not very representative nationally and in many locations. Representativeness could be improved by increasing participation in more states and among specific types of hospitals. (Disaster Med Public Health Preparedness. 2016;10:562–569)
GENERALIZED EXPLICIT DESCENT AND ITS APPLICATION TO CURVES OF GENUS 3
Authors: BRUIN NILS , POONEN BJORN , STOLL MICHAEL
Published: February 2016

We introduce a common generalization of essentially all known methods for explicit computation of Selmer groups, which are used to bound the ranks of abelian varieties over global fields. We also simplify and extend the proofs relating what is computed to the cohomologically defined Selmer groups. Selmer group computations have been practical for many Jacobians of curves over $\mathbb{Q}$ of genus up to 2 since the 1990s, but our approach is the first to be practical for general curves of genus 3. We show that our approach succeeds on some genus 3 examples defined by polynomials with small coefficients.
Experiments in rotating plane Couette flow – momentum transport by coherent roll-cell structure and zero-absolute-vorticity state
Authors: Kawata Takuya , Alfredsson P. Henrik
Published: February 2016

In spanwise rotating plane Couette flow (RPCF) a secondary flow dominated by three-dimensional roll-cell structures develops. At high enough rotation rates the flow exhibits a state of zero absolute vorticity at the centre of the channel, as described by Suryadi et al. (Phys. Rev. E, vol. 89, 2014, 033003). They suggested that the zero-absolute-vorticity state is caused by the secondary flow motion of the coherent roll-cell structure induced by the Coriolis force. In the present study we focus on the momentum transport caused by the roll-cell structure of laminar RPCF in order to further understand how the zero-absolute-vorticity state is maintained by the coherent roll cells. The flow is studied through stereoscopic particle image velocimetry measurements, which allow both the Reynolds shear stress and the wall shear stress to be quantified and used as measures of the momentum transport across the channel. Various types of roll-cell structures at different system rotation rates and the momentum transport induced by them are investigated, and the processes in which the momentum is transported in the wall-normal direction are discussed based on a displaced-particle argument as well as the production of the Reynolds stresses. It is shown that the wall-normal fluid motion driven by secondary flow of the roll-cell structure induces two different effects on the mean flow which conflict each other, the momentum transport in the wall-normal direction and the Coriolis acceleration, and the zero-absolute-vorticity state is a stable state where these two effects cancel each other.
Separating Candidate Valence and Proximity Voting: Determinants of Competitors’ Non-Policy Appeal
Authors: Nyhuis Dominic
Published: February 2016

Previous scholarship has provided ample evidence that non-spatial considerations can trump voters’ policy preferences in candidate selections. The literature has been less successful, however, in providing a sense of the factors that raise candidates’ non-policy appeal. Faced with the challenging task of separating policy and non-policy aspects of individual vote choices, empirical research has frequently relied on shorthand measures like candidate incumbency. This paper separates the valence component from policy-based candidate selections by explicitly supplying voters with information on the policy agreement between themselves and their district candidates. Relying on the distinction between campaign valence and character valence by Stone and Simas, it is shown that candidate valence is driven by candidate visibility in a party-dominated political system.
Trust and Obey: Toward a New Theory of Punishment
Authors: Hoekema David A.
Published: February 2016

An impartial observer reviewing the Anglo-American philosophical writings of recent decades on the question of the justification of punishment would very likely label the contest, thus far, a draw. Three major justifications have been put forward as principles constitutive of fairness in punishment, and none can be said to have routed its rivals.

Some modern writers have written forcefully in defence of the rehabilitative justification of punishment — or, more precisely, the replacement of punishment with a system of judicially mandated therapy for criminals. This substitution, however, has been tellingly criticized as demeaning to offenders, violative of individuals' moral rights, and liable to abuse as a pretext for suppression of unpopular ideas. Others have sought to justify punishment on the basis of the societal need to deter crime. But deterrence seems at the same time too severe and too lenient a basis for punishment. Draconian penalties for minor offences and exemplary punishment of the innocent would meet the requirements of deterrence if they proved effective in preventing future crimes; yet offences whose nature or whose pattern of occurrence makes effective deterrence impossible should go unpunished, on this view.
Frontal Behavioral Inventory: Diagnostic Criteria for Frontal Lobe Dementi
Authors: Kertesz Andrew , Davidson Wilda , Fox Hannah
Published: February 2016

ABSTRACT:

Objective:

To utilize the diagnostic criteria of frontal lobe dementia (FLD).

Methods:

We studied 12 patients with FLD diagnosed clinically, with radiological confirmation in 10 and autopsy confirmation in 2; sixteen patients with Alzheimer's disease matched for stage and severity to FLD and 11 patients with depressive dementia were used as control groups. A 24-item Frontal Behavioral Inventory (FBI) using the most relevant behavioral manifestations of FLD was administered in these populations.

Results:

FLD patient scores on the FBI were much higher compared with control groups (AD and DD). Item analysis showed loss of insight, indifference, distractibility, personal neglect and apathy as the most frequent negative symptoms. Perseveration, disinhibition, inappropriateness, impulsivity, and irresponsibility were the most significant positive symptoms. An operational definition of FLD included a minimum FBI score of 27. Only one false positive was shown in the depressive group and none among the AD group, indicating little overlap between patient groups, and a high discriminating value of the FBI.

Conclusions:

The FBI appears to be a useful diagnostic instrument and a method to operate the behavioral criteria of FLD. Further prospective studies are warranted to establish validity.
Measuring Bias in Uncontrolled Brain Tumor Trials – to Randomize or Not to Randomize?
Authors: Irish William D. , Macdonald David R. , Cairncross J. Gregory
Published: February 2016

Purpose:

To help investigators decide if new therapies for glioma warrant definitive evaluation in randomized studies we have been developing a method for assessing the degree to which patient selection may have enhanced the results of uncontrolled treatment trials. In this study, we analyzed the impact of case selection on the survival of patients with malignant glioma receiving adjuvant stereotactic radiosurgery, a promising therapy reserved for those with small tumors and good performance status.

Methods:

Following published eligibility criteria we simulated the patient selection process for stereotactic radiosurgery given as a boost at the conclusion of conventional radiotherapy. Eligible patients were culled from a pre-existing clinical/imaging database of 101 consecutive conventionally-treated patients with biopsy-proven malignant glioma and known survival times. Median durations of survival and 2- and 3-year survival rates were determined for those judged eligible or ineligible for stereotactic radiosurgery.

Results:

Twenty-seven percent of patients were deemed eligible for stereotactic radiosurgery, eligible patients had more favorable prognostic factors and significantly longer median survival than ineligible patients (23.4 vs. 8.6 months; 2-year rate, 48% vs. 15%; 3-year rate, 30% vs. 7%); eligible patients also had a longer median survival than the entire group of unselected patients (23.4 vs. 11.4 months). Radiosurgery-eligible, conventionally-treated patients with glioblastoma multiforme and a group of radiosurgery-treated patients at a special referral center had similar median survival times (16.4 vs. 19.7 months).

Conclusion:

We provide additional evidence for selection bias in uncontrolled trials of stereotactic radiosurgery and by simulating the selection process accurately have detected a larger bias effect than noted previously. Judging from experience with interstitial radiation and intraarterial chemotherapy where substantial selection bias also occurred and randomized controlled trials proved disappointing, we conclude that a phase III study of stereotactic radiosurgery for malignant glioma is unlikely to yield a positive result and may not be necessary.
Prognostic Factors in Oligodendroglioma
Authors: Schiffer D. , Dutto A. , Cavalla P. , Bosone I. , Chiò A. , Villani R. , Bellotti C.
Published: February 2016

Background:

A reliable marker for tumor oligodendroglial cells is not yet available, so that the histological recognition of the tumor still encounters uncertainties. There is no general agreement also on prognostic factors in oligodendroglioma. The inconsistency concerns mainly the histopathological factors. The aim of the study was recognition of prognostic factors in oligodendroglioma.

Methods:

In a series of ninety-eight oligodendrogliomas, including twenty mixed oligoastrocytomas, clinical [sex, age at surgery, tumor location, symptoms at presentation], therapeutic [extent of resection, year of surgery, post-operative Karnofsky score, post-operative radiotherapy, post-operative chemotherapy], histological [cell density, nuclear pleomorphism, vascular endothelial proliferation, necrosis, microcysts, mitoses, mitotic index (MI), apoptosis, apoptotic index (AI)] and immunohistochemical parameters [MIB-1 and PCNA Labeling Indexes (Lis), staining for GFAP, positivity for p53] were correlated with survival in uni- and multivariate analysis in order to identify their prognostic significance.

Results:

Age at surgery, extent of surgical resection, year of surgery, postoperative Karnofsky score and MIB-1 LI were associated with survival in both uni- and multivariate analysis. Location, symptoms at presentation, mitoses, MI, AI, and PCNA LI showed a significant correlation with survival in uni- but not in multivariate analysis. The twenty cases of oligoastrocytomas did not show any difference in survival from pure oligodendrogliomas.

Conclusions:

Some clinical and therapeutic factors together with MIB-1 LI play a prognostic role. MIB-1 LI is prognostic with a cutoff of 8%. Histology gives a limited contribution to the prognosis. Oligoastrocytomas had the same outcome and prognostic factors as pure oligodendrogliomas.
An Electroencephalographic Classification for Coma
Authors: Young G.B. , McLachlan R.S. , Kreeft J.H. , Demelo J.D.
Published: February 2016

Background:

The assessment of thalamocortical function in comatose patients in the intensive care unit (ICU) can be difficult to determine. Since the electroencephalogram (EEG) affords such assessment, we have developed an EEG classification for comatose patients in our general ICU.

Methods:

One hundred EEGs were classified in a blinded fashion by two EEGers, using our method and that of Synek. Interobserver agreement was assessed using kappa score determination.

Results:

Kappa scores were 0.90 for our system and 0.75 for the Synek system. (The Kappa score represents the inter-rater agreement that is beyond chance; 0.90 is almost perfect agreement, while 0.75 is substantial agreement).

Conclusion:

Our system for classifying EEGs in comatose patients has a higher interobserver reliability than one that was previously published. This EEG classification scheme should be useful in clinical electrophysiological research involving ICU patients, allowing for internal consistency and comparisons among centres.
Motor Pathway Analysis in HAM/TSP Using Magnetic Stimulation and F-waves
Authors: Young Ronald E. , Morgan Owen C. , Forster Allan
Published: February 2016

Background:

Tropical Spastic Paraparesis/HTLV-I Associated Myelopathy (HAM/TSP) is a chronic, progressive myelopathy endemic to the Caribbean. In HAM/TSP, peripheral motor pathways have been assessed using electromyography and nerve conduction studies; central motor pathways have been assessed to a limited extent using electrocortical stimulation. We used magnetic cortical stimulation (a painless alternative to electrocortical stimulation) and F-wave analysis to study conduction in the central and peripheral motor pathways in 18 HTLV-I seropositive, Jamaican TSP patients (ages 29- 70 years; duration of symptoms 3-20 years) and 22 normal controls.

Methods:

Magnetic cortical stimulation was effected using a 9 cm diameter undamped MES10 coil. F-waves and M-responses were elicited by electrical stimulation of the ulnar nerve at the wrist, and deep peroneal stimulation at the knee. Stimulation and recording of response latencies in abductor digitii minimi (ADM) and tibialis anterior (TA) were carried out using a Cadwell Excel system.

Results:

With cortical stimulation, response latencies (TMCTs) to ADM and TA were prolonged in the patients relative to controls. F-wave and M-response latencies were unaffected, suggesting no peripheral pathology. Latency (CMCT) between cortex and lumbar cord was significantly prolonged; that between cortex and C7/T1, also, but less markedly (P < 0.0005). Amplitudes of cortically evoked responses were significantly reduced only in the lower limbs (TA). CMCT increased as the disease progressed from mild to moderate, thereafter remaining largely unchanged.

Conclusions:

Meta-analysis of interlaboratory control data revealed no significant differences in TMCTs between our controls and others studied using similar techniques. The observations are consistent with pathology affecting mainly the thoracolumbar cord in HAM/TSP.
Adenosine and Migraine
Authors: Guieu R. , Devaux C. , Henry H. , Bechis G. , Pouget J. , Mallet D. , Sampieri F. , Juin M. , Gola R. , Rochat H.
Published: February 2016

Background:

Adenosine is a powerful natural vasodilator that participates in the control of cerebral and meningeal blood flow. In this context, it could be involved in the pathophysiology of migraine, since it was previously reported that intravenous adenosine can precipitate crises in migraine patients.

Methods:

We have investigated circulating adenosine levels in 12 patients suffering from migraine without aura, during crises and in crisis-free periods, and have compared the levels noted to those of a population of 10 controls. To determine if there are interactions between adenosine and serotonin, we examined the effect of adenosine and antagonists on the uptake and the release of (14C) serotonin by platelets.

Results and conclusions:

We have reached a dual conclusion: 1) during migraine headaches there is an increase (mean 68%) in circulating adenosine levels and this increase may participate in cephalalgia; 2) activation of A2 receptors by adenosine causes a dose-dependent inhibition of calcium-dependent serotonin uptake by platelets. This inhibition of uptake could participate in the rapid elimination of serotonin in migraine sufferers. As a result of this, the use of adenosine antagonists could be an effective complementary treatment for migraine.
The Frequency of Phospholipid Antibodies in an Unselected Stroke Population
Authors: Metz L.M. , Edworthy S. , Mydlarski R. , Fritzler M.J.
Published: February 2016

Background:

Antibodies to cardiolipin and other phospholipids have been associated with recurrent thrombotic events, including stroke.

Methods:

Over a 16 month period we assessed an unselected cohort of 151 ischemic stroke patients for the presence of antiphospholipid antibodies. Patients with known systemic lupus erythematosis, systemic sclerosis, or Sjogrens Syndrome were excluded. Sera from patients admitted to hospital with a diagnosis of ischemic stroke (n = 151) and from controls (n = 111) assessed during the same period were tested for antiphospholipid antibodies (APLA) using 3 assays; anticardiolipin antibodies (ACA) by ELISA, prolonged activated partial thromboplastin time (APTT), and VDRL.

Results:

The average age of ischemic stroke cases was 68 years (range 29 to 91) and of controls 63 years (range 29 to 86). The prevalence of APLA detected by at least one of the three methods was 12% for IS cases and 10% for controls. After correcting for known risk factors such as age, gender, diabetes mellitus, heart disease, hypertension, and smoking, the odds ratio for risk of stroke fell to 0.8 (C.I. 0.4 to 1.2).

Conclusions:

Our findings suggest that APLA may not be an independent risk factor for ischemic stroke in unselected persons who do not have known systemic lupus erythematosis or systemic sclerosis but further evaluation of the role of lupus anticoagulant is indicated.
Ischemic Neuronal Injury is Ameliorated by Astrocyte Activation
Authors: Louw Deon F. , Masada Tetsuy , Sutherland Garnette R.
Published: February 2016

Background:

The motivation of this study was to more precisely define the in vivo role of astrocytes in forebrain ischemia. Controversy exists in the literature as to whether they protect or injure neurons in this setting.

Methods:

Astrocytes in the rat hippocampus were disabled with stereotactic administration of a gliotoxin, ethidium bromide, 3 days prior to induction of forebrain ischemia. The extent of neuronal injury in this group was compared to a control category receiving intrahippocampal saline only.

Results:

Saline-injected animals demonstrated decreased hippocampal CA1 sector injury, and increased gliosis on the side of the injection compared to the contralateral side (P < 0.01) or ethidium bromide-treated animals (P < 0.05).

Conclusion:

The results suggest that activated astrocytes are protective to neurons subjected to an ischemic insult. This may result from their ability to elaborate neurotrophic factors, buffer potassium and metabolize a variety of neurotransmitters.
Epidemiology and Direct Economic Impact of Hydrocephalus: A Community Based Study
Authors: Bigio Marc R. Del
Published: February 2016

Background:

The cost of care for hydrocephalic patients is not well established.

Methods:

This retrospective study for the years 1990-1996 analyzed the cost of surgical intervention and hospitalization of hydrocephalic patients in the community-based setting of Manitoba, Canada, with a stable population of 1.138 million.

Results:

The number of discharges with a primary diagnosis of hydrocephalus was greater than 200 annually. The mean duration of hospital stay was 12.4 to 21.9 days, depending on the etiology of hydrocephalus. Approximately 80 shunt procedures were performed annually. The total annual cost of care, excluding outpatient costs and chronic non-hospital based costs which could not be determined accurately, was estimated to be CDN$ 3.5 million in this community.

Conclusion:

Hydrocephalus is a chronic condition which puts substantial monetary demands on society and therefore deserves greater attention.
In-Patient Treatment of Chronic Daily Headache Using Dihydroergotamine: a Long-term Follow-up Study
Authors: Pringsheim Tamara , Howse David
Published: February 2016

Background:

The treatment of chronic daily headache (CDH) due to medication overuse remains a common and difficult problem. For selected patients refractory to outpatient management we have used a treatment protocol using dihydroergotamine (DHE) as introduced by Raskin, during a brief (typically 48 hours) in-patient stay. While many studies have documented the short-term efficacy of the DHE protocol, there are limited data on its long-term effects. The purpose of this study was to evaluate the efficacy of the protocol on headache frequency and severity, analgesic use, absences from work, and quality of life, at three months post treatment and the present time.

Methods:

A retrospective chart review of all patients admitted for the DHE protocol from 1991 to 1996 revealed 174 cases. Of these, 132 patients were interviewed by phone.

Results:

The DHE protocol was shown to decrease headache frequency, severity, headache medication use, and absences from work both at three months and the time of interview.

Conclusion:

This study has the largest patient base and the longest follow-up period for the use of DHE for CDH. The results confirm that the DHE protocol is helpful in breaking the cycle of CDH, although the long-term outcomes of this study are more conservative than other studies have reported.
Neurofibromatosis Type 1: Piecing the Puzzle Together
Authors: Feldkamp Matthias M. , Gutmann David H. , Guha Abhijit
Published: February 2016

Neurofibromatosis type 1 (NF1) was first described in 1882 and is characterized by a diverse spectrum of clinical manifestations, including neurofibromas, cafe au lait spots, and Lisch nodules. NF1 is also noted for the higher risk of associated malignancies, making it the most common tumour-predisposing disease in humans. Transmitted in an autosomal dominant manner, the NFI gene was cloned in 1990, and belongs to the family of tumour suppressor genes. Since then, there has been an explosion in our understanding of how the gene product, neurofibromin, functions in normal cellular physiology, and how its loss in NF1 relates to the wide spectrum of clinical findings, including NF1-associated tumours. Neurofibromin is a major negative regulator of a key signal transduction pathway in cells, the Ras pathway, which transmits mitogenic signals to the nucleus. Loss of neurofibromin leads to increased levels of activated Ras (bound to GTP), and thus increased downstream mitogenic signaling. Our understanding of neurofibromin's role within cells has allowed for the development of pharmacological therapies which target the specific molecular abnormalities in NF1 tumours. These include the farnesyl transferase inhibitors, which inhibit the post-translational modification of Ras, and other agents which modulate Ras-mediated signaling pathways.
Ethical Guidelines of the Alzheimer Society of Canada
Authors: Fisk John D. , Sadovnick A. Dessa , Cohen Carole A. , Gauthier Serge , Dossetor John , Eberhart Astrid , LeDuc Linda
Published: February 2016

Alzheimer's disease raises numerous ethical issues which vary and evolve over the course of the illness. In recognition of the need for ongoing discussion of these issues, the Alzheimer Society of Canada established a Task Force on Ethics in 1995. Through a process of “discourse ethics” and consultation on a national scale, the Task Force produced a series of guidelines dealing with the issues of: communicating the diagnosis, driving, respecting individual choice, quality of life, participation in research, genetic testing, the use of restraints, and end-of-life care. This manuscript presents a summary of these guidelines as well as a summary of the ideas on which they were based. It was the hope of the Society that the publication of these guidelines will serve to facilitate discussion of the ethics of care of those with Alzheimer's disease.
Seronegative Myasthenia Gravis and Human Immunodeficiency Virus Infection: Response to Intravenous Gamma Globulin and Prednisone
Authors: Strong James , Zochodne Douglas W.
Published: February 2016

Background:

There are only rare reports of myasthenia gravis complicating human immunodeficiency virus infection. The role of immunomodulatory therapy is unknown.

Methods:

Case report and literature review.

Results:

The diagnosis of human immunodeficiency virus infection followed that of myasthenia gravis in a 35-year-old man. Clinical and electrophysiological features were diagnostic of generalized myasthenia gravis but two edrophonium chloride tests and acetylcholine receptor antibodies were negative. Prednisone therapy and intravenous gamma globulin were associated with rapid clinical recovery.

Conclusions:

Prednisone therapy and intravenous gamma globulin may be helpful in patients with generalized myasthenia gravis complicating HIV infection.
Canadian Guidelines for Intravenous Thrombolytic Treatment in Acute Stroke: A Consensus Statement of The Canadian Stroke Consortium
Authors: Norris J.W , Buchan A. , Cote R. , Hachinski V. , Phillips S.J. , Shuaib A. , Silver F. , Simard D. , Teal P.
Published: February 2016

Background:

The thromobolytic drug, tissue plasminogen activator (tPA) has been approved in the United States for the treatment of acute ischemic stroke amid controversy and concern about the balance of risk and benefit. The Canadian Stroke Consortium (CSC), a national network of neurologists who collaborate on joint projects in stroke medicine, including clinical trials and consensus statements, has developed guidelines for the use of tPA in Canada.

Methods and Results:

The CSC Board of Directors wrote a preliminary report based on existing publications, including randomized drug trials and the report of a special committee struck by the Stroke Council of the American Heart Association. This draft was circulated to the CSC membership-at-large for suggestions or amendments, to produce this final draft.

Conclusions:

The present guidelines have been devised to represent a Canadian viewpoint of management. The Health Protection Branch of the Ministry of Health of Canada has not yet produced an evaluation. Further modification of these guidelines may be necessary when more data from clinical trials and experience with the drug become available.
Seizure Exacerbation and Developmental Regression with Carbamazepine
Authors: Prasad A.N. , Stefanelli M. , Nagarajan L
Published: February 2016

Background:

Unexpected exacerbation of seizures may occur following initiation of treatment with carbamazepine (CBZ). We reviewed the occurrence of such reactions in our patient population at a tertiary care children's hospital.

Methods:

A retrospective analysis of our clinic database identified 129/691 (18.6%) patients with epilepsy treated with CBZ, as monotherapy. 38/129 children were later switched to another drug. In 11/38 (28.5 %) clinical and/or EEG deterioration was observed. Two patients identified at another institution with similar exacerbation were also included in our analysis. We report on the findings in these 13 cases.

Results:

Two groups were identified: Group I - 6 patients with normal neurological exam, normal EEG background, and a diagnosis of idiopathic generalized epilepsy. Group II - 7 patients with an abnormal neurological exam and/or abnormal EEG background. Following introduction of CBZ therapy, worsening of preexisting seizures, appearance of new seizure types, behavioral regression, and accompanying EEG deterioration were reported in both groups. Dramatic improvement in seizure control occurred, following withdrawal of CBZ and substitution of another anticonvulsant.

Conclusion:

Physicians treating epilepsy must be aware that CBZ can exacerbate seizures, and cause developmental regression in children. Careful patient selection, when choosing CBZ as treatment, and prompt recognition of clinical deterioration and intervention, may help avoid or reverse these paradoxical reactions.
Subcortical Vascular Dementia: Survey of Treatment Patterns and Research Considerations
Authors: Molnar Frank J. , Man-Son-Hing Malcolm , John Phil , Brymer Chris , Rockwood Kenneth , Hachinski Vladimir
Published: February 2016

Background:

Since few studies have examined the effectiveness of therapies for subcortical vascular dementia, treatment guidelines are not available. Current patterns in the treatment of such dementias have not been studied.

Objective:

To determine the practice patterns of Canadian specialists for the treatment of subcortical vascular dementia, and to survey their opinions regarding issues which are important in the design of a randomized controlled trial (RCT) in this field.

Design:

National survey of all specialists certified in Neurology or Geriatric Medicine.

Results:

Of responding physicians (78%) prescribed antithrombotic therapy for patients with vascular dementia. Most begin treatment with aspirin 325 mg daily (64%). The next three most common initial treatments were; no pharmacotherapy (12%), aspirin 650 mg daily (11%), and aspirin 1300 mg daily (11%). If the dementia continued to progress despite initial therapy, the treatment options were more varied. Most specialists (69%) believed that an RCT to assess the efficacy of aspirin in vascular dementia is warranted. The majority (69%) also felt that serial neuroimaging would be required for participants in such a trial, with magnetic resonance imaging being cited most frequently (41%). The majority of specialists considered three years as the minimum durationb for such a trial.

Conclusions:

Specialist physician practice patterns vary significantly for the treatment of patients with subcortical vascular dementia. Most physicians believe that an RCT testing the efficacy of aspirin in this condition is required. However, before such a trial can be conducted, many methodological difficulties need to be addressed.
Topiramate Use in Pediatric Patients
Authors: Glauser Tracy A.
Published: February 2016

Topiramate (TPM), a new antiepileptic medication, is efficacious as adjunctive therapy in adults with partial onset seizures. Its efficacy as adjunctive therapy in children was evaluated in two randomized double-blind placebo-controlled trials involving childhood epileptic encephalopathy (the Lennox-Gastaut syndrome) and partial onset seizures. In these studies, topiramate adjunctive therapy resulted in a significant reduction in drop attacks (tonic or atonic seizures) in patients with the Lennox Gastaut syndrome and a significant reduction in partial onset seizures in children with refractory partial epilepsy. In both trials, TPM's efficacy improved as the dose escalated from the double-blind phase to the open-label portion. The minimally effective topiramate dose for adjunctive therapy in children with refractory epilepsy appears to be 6 mg/kg/day. Topiramate was well tolerated with mild or moderate side effects, predominantly related to the central nervous system. Practical tips are provided that may increase the chance that topiramate will be effective and well tolerated. The most important advice is a “start low, go slow” approach. An initial TPM dose of 0.5 - 1 mg/kg/day followed by weekly increments of 0.5 - 1 mg/kg is usually well tolerated. Based on these studies, topiramate appears to be an important addition to our pediatric AED armamentarium.
Topiramate - Safety and Tolerability
Authors: Jones M.W.
Published: February 2016

Topiramate is a new novel drug for the treatment of intractable seizures that is to be used in an adjunctive fashion. A review of the seven double-blind controlled studies was undertaken with special attention paid to safety and tolerability data. The studies were similar in design but used varying doses of the drug. To date there has been no evidence of serious systemic side effects such as rash, hepatotoxicity, cardiotoxicity, serious gastrointestinal toxicity or aplastic anemia. Renal stones were reported in 1.5% of patients with over 80% choosing to remain on the drug because of an improved quality of life. The unique observation of “abnormal thinking” was seen that seemed to be related to high doses and introducing the drug too rapidly. Patients, rather than describing psychomotor slowing, described a phenomenon of slow thoughts, decreased cognition, intermittent difficulty calculating, dulled thinking, blunted mental reactions. Lastly, weight loss appears in approximately 10-20% of patients and is probably related to dulling of appetite. Although increasing doses gave increasing degrees of seizure freedom, it appeared that doses beyond 600 mg/day are often not well tolerated.
Risk Factors for Peak Dose Dyskinesia in 100 Levodopa-treated Parkinsonian Patients
Authors: Blanchet Pierre J. , Allard Pierre , Grégoire Laurent , Tardif François , Bédard Paul J.
Published: February 2016

Background: No clinical parameter other than “sufficient” dopamine denervation and exposure to exogenous levodopa has been unquestionably linked to dyskinesia in levodopa-treated Parkinson’s disease patients.Methods: We retrospectively analyzed data on 100 consecutive patients treated with levodopa for 1 to 18 years to identify clinical risk factors for dyskinesia. The cumulative dyskinesia-free survival probability in relation to levodopa therapy was assessed using the Kaplan-Meier method.Results: Overall, 56% of patients developed dyskinesia after a mean of 2.9 years, a figure similar to the average duration of levodopa treatment in the non-dyskinetic group. Dyskinetic patients were significantly younger at disease onset, but their mean latency to dyskinesia induction after levodopa initiation was not different from older dyskinetic individuals and the overall dyskinesia-free survival of younger subjects was not worse either. Dyskinetic patients were on a higher daily levodopa dose than non-dyskinetic subjects when dyskinesia emerged, but the cumulative levodopa dose used prior to dyskinesia did not discriminate dyskinetic from non-dyskinetic patients. A delay in initiating levodopa therapy of more than three years after disease onset and levodopa treatment initiation in Hoehn-Yahr stage II compared to stage I patients did not increase the probability of developing dyskinesia over time.Conclusions: Since withholding levodopa therapy did not increase the risk for dyskinesia in our patients and can delay the emergence of dyskinesia after onset of parkinsonian symptom, a trial with a dopaminomimetic agonist as initial treatment appears logical.
Listeria Spinal Cord Abscess – Clinical and MRI Findings
Authors: Chu Joseph Y. , Montanera Walter , Willinsky Robert A.
Published: February 2016

Background: Intramedullary spinal cord abscess due to Listeria Monocytogenes is an uncommon condition usually affecting immunocompromised patients. Method: Case study. Results: A 69-year-old man presented with 3 weeks history of subacute paralysis of both lower limbs and the left upper limb. Myelogram and CT scan showed a widened upper cervical cord. CSF revealed lymphocytosis, moderately elevated protein and depressed glucose. A gadolinium-enhanced MRI showed diffuse cervical cord edema with two ring-enhancing lesions at C2-C3. Blood and CSF cultures grew Listeria Monocytogenes. He received IV ampicillin and gentamycin; the latter was discontinued after 1 month due to nephrotoxicity. Serial MRI over the next 3 months showed significant reduction in the size of these abscesses. The patient made a modest improvement in the power of his lower limbs, however he remained bed-ridden. Aside from being a mild, diet-controlled diabetic, there was no evidence of immunosuppression. Conclusion: Listeria spinal cord abscess is a treatable disorder and should be considered in the differential diagnosis in patients with a subacute onset of spinal cord dysfunction.
Headache and Scalp Edema in Sickle Cell Disease
Authors: Pari Giovanna , Schipper Hyman M.
Published: February 2016

Background: Major neurological complications of sickle cell disease include cerebral infarction and intracranial hemorrhages.Methods: We describe the case of a 25-year-old man with sickle cell disease who developed a severe headache of acute onset, located at the vertex. There was associated pitting edema of the scalp.Results: Technetium and gallium bone imaging showed focal decreased uptake of the tracers, consistent with a recent fronto-parietal skull infarction. Management included intravenous hydration and analgesic medication.Conclusions: In addition to the more common intracranial vaso-occlusive complications, skull infarction should be considered as a cause of new-onset headache in patients with sickle cell disease, especially if scalp edema is present.
Blood Manganese Correlates with Brain Magnetic Resonance Imaging Changes in Patients with Liver Disease
Authors: Hauser Robert A. , Zesiewicz Theresa A. , Martinez Carlos , Rosemurgy Alexander S. , Olanow C.W.
Published: February 2016

Background: Chronic liver failure is associated with high signal abnormalities in the basal ganglia on Tl-weighted magnetic resonance imaging of the brain. These abnormalities are strikingly similar to those seen following manganese intoxication. As dietary manganese is normally cleared by the liver, we hypothesize that hepatic dysfunction could lead to manganese overload and account for the MR1 abnormalities seen in patients with chronic liver disease.Methods: We measured blood manganese concentrations in eleven patients with biopsy-proven hepatic cirrhosis and eleven healthy age and sex-matched controls. We also performed semi-quantitative measures of Tl signal abnormalities on MRI in the patients with chronic liver disease.Results: Patients with cirrhosis had significantly higher blood manganese concentrations (20.6 ± 10.2 mcg/L) than controls (7.2 ± 2.7, p = .0013). In addition, semi-quantitative scores of TI-weighted signal hyperintensity on MRI correlated with blood manganese concentration in patients with cirrhosis (r = .65, p = .029).Conclusions: These findings demonstrate that chronic liver disease is associated with manganese overload and suggest that manganese is responsible for the Tl-weighted signal hyperintensity seen on MRI of patients with liver disease. As manganese intoxication is known to cause parkinsonism and an encephalopathy similar to those which occur with chronic liver disease, it is possible that manganese toxicity contributes to the development of these symptoms in liver damaged patients and that therapies which prevent or reduce manganese overload may have clinical benefit.
Paraneoplastic Limbic Encephalitis in Hodgkin’s Disease
Authors: Deodhare Sanjeev , O’Connor Paul , Ghazarian Danny , Bilbao Juan M.
Published: February 2016

Background: Oat cell carcinoma of the lung is the most common cause of paraneoplastic limbic encephalitis. Association with other malignancies, in particular Hodgkin’s disease, is very rare. Case Report: This 23-year-old male presented with a six month history of progressive alteration in mental status, which consisted of insomnia, short-term memory loss, depression and cognitive impairment. Gadolinium MRI of the head showed intense bilateral contrast enhancement affecting the medial aspects of the temporal lobes in the region of the amygdala and hippocampus. The brain biopsy showed minimal neuronal loss with intense perivascular lymphocytic cuffing and microglia] nodules. Polymerase chain reaction for herpes simplex and cytomegalovirus were negative. With prednisone treatment, the patient’s neurologic status stabilized but did not improve. Four months later, he presented with left axillary lymphadenopathy. Lymph node biopsy was diagnostic of Hodgkin’s disease. During the chemotherapy, his lymphadenopathy subsided and his neurologic and mental status improved. When seen last after completion of his chemotherapy, one year after presentation, he had resumed normal social activities and was enrolled in a university language course. Conclusion: This is the first reported case in the English literature of a biopsy proven paraneoplastic limbic encephalitis associated with Hodgkin’s disease. Hodgkin’s disease should be thought of as a possible cause of paraneoplastic limbic encephalitis in the appropriate clinical setting.
Tirilazad Prevention of Reperfusion Edema After Focal Ischemia in Cynomolgus Monkeys
Authors: Boisvert Donald P. , Hall Edward D.
Published: February 2016

Background:

The purpose of the present investigation was to determine if post-ischemic treatment with the 21-aminosteroid lipid peroxidation inhibitor tirilazad mesylate (U-74006F) could affect reperfusion brain edema during the first 3h following a 3h period of middle cerebral artery occlusion-induced focal ischemia in cynomolgus monkeys.

Methods:

Adult female cynomolgus monkeys (N = 14) were subjected under halothane anesthesia to a 3h period of middle cerebral artery occlusion, followed by 3h of reperfusion. U-74006F, 3.0 mg/kg i.v. or citrate vehicle, was administered 10 min before beginning reperfusion. Multiple spin-echo (8 echoes: TE = 26.3 msec; TR = 3.0 sees; 2.35 Tesla) magnetic resonance imaging was performed every 30 min, beginning at lh after reperfusion. Transverse relaxation rates (T2) for the caudate, putamen, cortex, insular cortex, parietal cortex and central white matter were calculated as an index of focal brain edema. After the final images, corresponding regions were removed for determination of water content by the wet weight/dry weight method.

Results:

The T2 measurements strongly suggested the presence of post-reperfusion edema in all gray matter, but not white matter, regions at 1 h after reperfusion in vehicle-treated animals. Significant attenuation of edema development was seen in the putamen and insular cortex in U-74006F-treated animals. An effect was also observed in the parietal cortex, but none in the caudate. The measurement of water content at 3h after reperfusion yielded similar results.

Conclusions:

These results showing the ability of U-74006F to attenuate post-reperfusion brain edema support the concept that lipid peroxidation is a significant mediator of reperfusion brain edema after focal ischemia. The therapeutic window for U-74006F’s anti-edema effect appears to be at least 3h after the onset of focal ischemia since delaying treatment until just before reperfusion largely prevented subsequent edema in cortical regions and the putamen. The effects of U-74006F on edema may play a mechanistic role in the compound’s reported neuroprotective efficacy in a variety of focal ischemia models.
Experimental Study of NADPH-Diaphorase Positive Neurons in Nucleus Accumbens of Rats
Authors: Zhao Yan , Huang Ke-Wei
Published: February 2016

Background

In order to explain the mechanism for the sparing of the nucleus accumbens in several pathologic conditions, the accumbens, caudate and putamen were examined in an experimental model.

Methods

The neurons in these regions from twenty adult rats were stained for the enzyme nicotinamide adenine dinucleotide phosphate (NADPH-diaphorase) and quantified.

Results

Positive neurons in the nucleus accumbens were more abundant than in the caudate and putamen.

Conclusions

Since these neurons have been shown to be resistant to ischemia and degeneration, it is suggested that the mechanism for the sparing of the nucleus accumbens is related to the presence of a large number of NADPH-diaphorase positive neurons.
Sudden Death in Multiple Sclerosis Associated with Sun Exposure: a Report of Two Cases
Authors: Avis Simon P. , Pryse-Phillips William EM.
Published: February 2016

Background

Two cases of sudden unexpected deaths in patients with multiple sclerosis were investigated by the Office of The Chief Forensic Pathologist.

Method

Case studies.

Results

Marked similarities of the deaths, including circumstances, scene examination, and autopsy findings including a complete drug screen were recorded.

Conclusions

Exposure to high ambient temperature may pose a danger to patients with multiple sclerosis. Mechanisms of death and the potential dangers to patients with clinically widespread disease are discussed.
Loss of Heterozygosity Analysis of Chromosomes 9, 10 and 17 in Gliomas in Families
Authors: Watling Christopher J. , van Meyel Donald J. , Ramsay David A. , Macdonald David R. , Cairncross J. Gregory
Published: February 2016

Background:

Studies of sporadic malignant gliomas have identified structural abnormalities in a number of chromosomal regions, especially losses of DNA on 9p, 10 and 17p.

Purpose:

We undertook the following molecular analysis in families with glioma to determine the frequency of chromosomal losses in these regions and to test the utility of microsatellite markers in demonstrating losses of heterozygosity.

Methods:

Genomic DNA was extracted from tumor tissue and venous blood from 20 patients with a family history of glioma. Dinucleotide repeat polymorphisms (microsatellites) were analyzed by polymerase chain reaction to assess loss of constitutional heterozygosity (LOH) on 9p, 10 and 17p. Three polymorphic markers on chromosome 9 (D9S104, D9S161, D9S165), one on chromosome 10 (D10S209), and two on 17p (D17S786, D17S796) were used. Autoradiographic films were analyzed for LOH after radioactively labelled polymerase chain reaction products were resolved on denaturing formamide-acrylamide gels.

Results:

Of 20 patients informative for at least one of three chromosome 9 markers, 12 (60%) showed LOH at one or more loci; of 9 informative for the chromosome 10 marker, 4 (44%) showed LOH; and of 16 informative for at least one of two chromosome 17 markers, 7 (44%) showed LOH at one or both loci. These LOH rates do not include instances of tumor nullizygosity (0 – 35%) and therefore represent minimum frequencies of chromosomal losses at these loci.

Conclusions:

Microsatellite markers can be used to detect LOH in archival glioma tissue. As in sporadic gliomas, frequent LOH was observed on 9p (9p21-22), 10 and 17p, supporting the notion that these regions may harbour tumor suppressor genes important in glioma development. Further work will be required to determine whether the proportion of LOH in these chromosomal regions is higher in familial gliomas than sporadic ones, as might occur with an inherited suppressor gene conferring susceptibility to gliomas in families.