European Neurological Journal Vol I Issue 1

Third-generation Antiepileptic Drugs for Partial-onset Seizures: Lacosamide, Retigabine, and Eslicarbazepine Acetate

Review Article

Steve S. Chung. Third-generation Antiepileptic Drugs for Partial-onset Seizures: Lacosamide, Retigabine, and Eslicarbazepine Acetate. The European Neurological Journal., September 2009; 1(1): 1-12

Affiliations: Department of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, USA

Submission date: 1st September 2009, Revision date: 17th September 2009, Acceptance date: 22nd September 2009

ABSTRACT

Despite the advent of new antiepileptic drugs (AEDs), more than 30% of epilepsy patients remain poorly controlled with current AEDs. For these patients, combined administration of AEDs or the application of novel AEDs are the most appropriate therapeutic options when surgical treatment cannot be offered. Second-generation and more recently developed AEDs tend to offer new mechanisms of action and more favorable safety profiles than the first-generation AEDs. The purpose of this article is to compare and review the information on the molecular mechanisms of action, pharmacokinetic profiles and the preliminary results of phase II and III clinical trials of three new AEDs – lacosamide (LCM), eslicarbazepine acetate (ESL), and retigabine (RTG).

Keywords: partial seizure, new anticonvulsant, lacosamide, eslicarbazepine acetate, retigabine, KCNQ channels, sodium channels
Correspondence: Steve S. Chung, MD, Department of Neurology, 500 West Thomas Road Suite 300, Phoenix, Arizona 85013, USA. Tel: +1-602-4066271; fax: +1-602-7980852; e-mail: sschunw.edu

The Impact of the Extended Time Window Seen in the ECASS III Trial on the Guidelines for Stroke Management in Europe

Original Manuscript

Keith W. Muir. The Impact of the Extended Time Window seen in the ECASS III Trial on the Guidelines for Stroke Management in Europe. The European Neurological Journal., September 2009; 1(1): 13-18

Keith W. Muir^1,2

Affiliations: ¹Division of Clinical Neurosciences, University of Glasgow, Glasgow, Scotland, UK; ²Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF, Scotland, UK

Submission date: 1st September 2009, Revision date: 5th September 2009, Acceptance date: 9th August 2009

 
ABSTRACT

Pooled analysis from the major randomized controlled trials of intravenous treatment with the recombinant tissue plasminogen activator alteplase for acute ischemic stroke showed a time-dependent benefit. Individual trials used windows of between 3 and 6 h from symptom onset and individually had only been conclusive for treatment within 3 h. The pooled analysis indicated that a significant improvement in the proportion of patients making an excellent recovery might extend to 4.5 h. The ECASS III trial recently confirmed benefit in the 3 to 4.5 h time window, with odds of excellent outcome of around 1.40, in line with predictions. There was no increase in risk of bleeding. Confirmation of safety in practice came from the Safe Implementation of Thrombolysis in Stroke–International Stroke Thrombolysis Register (SITS-ISTR) analysis of patients treated between 3 and 4.5 h. In response to these data, European and other guidelines have been updated to recommend treatment in patients up to 4.5 h after onset of symptoms who otherwise fulfill current European license terms. A formal change in licensed indications is awaited.

Keywords: stroke, cerebrovascular disease, guidelines, thrombolysis, alteplase, recombinant tissue plasminogen activator, rt-PA, acute treatment
Correspondence: Professor Keith Muir, Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF, Scotland, UK. Tel.: +44-141-201-2494; fax: +44-141-201-2510; e-mail: k.muir@clinmed.gla.ac.uk

Obesity, Diet, and Risk of Restless Legs Syndrome

Xiang Gao and Shivani Sahni. Obesity, Diet, and Risk of Restless Legs Syndrome. The European Neurological Journal., September 2009; 1(1): 59-64

Review Article

Obesity, Diet, and Risk of Restless Legs Syndrome

Xiang Gao^1,2 and Shivani Sahni ³

Affiliations: ¹Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA; ²Department of Nutrition, Harvard University School of Public Health, Boston, MA; ³Musculoskeletal Research, Institute for Aging Research, Hebrew SeniorLife, and Harvard Medical School, Boston, MA, USA

Submission date: 26th June 2009, Revision date: 16th August 2009, Acceptance date: 3rd September 2009

ABSTRACT

The restless legs syndrome (RLS) is a common movement disorder, characterized by an almost irresistible urge to move the legs in the evening or at rest. According to recent estimates, it affects ~5-15% of adults and often has a substantial impact on sleep, daily activities, and quality of life. Although genetic susceptibility has been shown to play an important role in the pathogenesis of RLS, there is evidence supporting possible environmental causes of RLS. In this review, we focus on obesity and dietary factors, including iron, B vitamins, vitamin E, vitamin C, and magnesium, as these factors are modifiable. Both clinical and epidemiology studies suggest that obesity and dietary factors could be risk factors for RLS. However, previous studies are limited by small sample sizes and retrospective or cross-sectional designs that preclude conclusions regarding causality. Therefore, further prospective studies examining the relation between obesity, diet, and the risk of developing RLS should be a priority.

Keywords: Obesity, diet, risk factor, restless legs syndrome, iron deficiency, homocysteine

Correspondence: Xiang Gao, Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA 02115, USA. Tel: +1-617-432-5080; fax: +1-617-432-2435; e-mail: xiang.gao@channing.harvard.edu

Neuroimaging of Primary Progressive Aphasia

Review Article

Jonathan D Rohrer and Nick C Fox. Neuroimaging of Primary Progressive Aphasia. The European Neurological Journal., September 2009; 1(1): 65-74

Jonathan D Rohrer and Nick C Fox

Affiliation: Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, UK

Submission date: 17th July 2009, Revision date: 20th August 2009, Acceptance date: 1st September 2009

ABSTRACT

In this review, we discuss the neuroimaging features of primary progressive aphasia (PPA), a group of neurodegenerative disorders characterized by an initial speech and language deficit. The PPA syndromes, semantic dementia (SD), progressive non-fluent aphasia (PNFA), and logopenic/phonological aphasia (LPA), are defined clinically, but there are emerging patterns of clinico-imaging–pathological correlation. Each of the PPA subtypes has a distinctive initial pattern of atrophy or hypometabolism affecting the left hemisphere language network that is consistent with the speech  and language and other cognitive/behavioral deficits present: SD is associated with disease affecting the anteroinferior temporal lobes, PNFA with the left insula and inferior frontal lobes, LPA with the left posterior superior temporal and inferior parietal lobes, and familial PPA caused by mutations in the progranulin gene with the left frontal, temporal, and parietal lobes. As we stand on the verge of clinical trials in PPA, the combination of structural, functional, and molecular imaging holds the promise of defining in vivo cohorts that are likely to have a common pathological target for disease-modifying treatments.

Keywords: primary progressive aphasia, frontotemporal dementia, frontotemporal lobar degeneration, logopenic aphasia, semantic dementia, progressive non-fluent aphasia
Correspondence: Nick Fox, Dementia Research Centre, Institute of Neurology, Queen Square, London WC1N 3BG, UK; Tel: +44-207-829-8773; fax: +44-207-676-2066; e-mail: nfox@dementia.ion.ucl.ac.uk

Frontal and Periventricular Brain White Matter Lesions and Cortical Deafferentation of Cholinergic and Other Neuromodulatory Axonal Projections

Subcortical Gliosis and Leukodystrophy Overlap Syndromes as a Cause of Late-onset Dementia

Russell H Swerdlow, Bradley B Miller, H Robert Brashear and Jeffrey M Burns. Subcortical Gliosis and Leukodystrophy Overlap Syndromes as a Cause of Late-Onset Dementia. The European Neurological Journal., September 2009; 1(1): 75-80

Russell H Swerdlow¹, Bradley B Miller², H Robert Brashear³ and Jeffrey M Burns¹

Affiliations: : ¹Departments of Neurology and Molecular and Integrative Physiology, University of Kansas School of Medicine, Kansas City, KS, USA; ²Department of Pathology, University of Virginia Health System, Charlottesville, VA, USA; ³Janssen Pharmaceutica, Titusville, NJ, USA

Submission date: 5th August 2009, Acceptance date: 24th August 2009


ABSTRACT

Neuroimaging is a routine part of the dementia syndrome evaluation. It frequently reveals perturbed white matter integrity. These perturbations, commonly referred to as leukoaraiosis or white matter disease, are often attributed to microvascular ischemia. When present, clinicians must decide whether white matter changes relate etiologically to clinical cognitive decline. We recently described a large autosomal dominant kindred in which multiple affected members were diagnosed initially with vascular dementia due to subcortical microischemic white matter disease. Subsequent  brain autopsies revealed subcortical gliosis, features suggestive of late-onset leukodystrophy, and a lack of microvascular ischemic disease. This review emphasizes that what is radiographically classified as microischemic white matter disease is not necessarily due to ischemia, and discusses the emerging realization that subcortical gliosis–leukodystrophy overlap syndromes can cause late-life dementia.

Keywords: dementia, frontotemporal dementia, hereditary leukodystrophy with axonal spheroids, leukoaraiosis, leukodystrophy, subcortical gliosis, white matter disease

Correspondence: Russell H Swerdlow, Landon Center on Aging, MS 2012, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. Tel: +1-912-588-6970; fax: +1-913-588-0681; e-mail: rswerdlow@kumc.edu

Restless Legs Syndrome and Peripheral Neuropathy—A Critical Review

ET Hattan, C Chalk and RB Postuma. Restless Legs Syndrome and Peripheral Neuropathy—A Critical Review. The European Neurological Journal., September 2009; 1(1): 51-56

ET Hattan¹, C Chalk² and RB Postuma²

Affiliations: ¹Section of Pulmonary and Critical Care Medicine, The University of Chicago Medical Center, Chicago, IL, USA; ²Departments of Neurology and Neurosurgery and Medicine, McGill University, Montreal General Hospital, Montreal, Quebec, Canada

Submission date: 21st June 2009, Revision date: 27th July 2009, Acceptance date: 7th August 2009


ABSTRACT

Much of our pathophysiologic understanding of the etiology of restless leg syndrome (RLS) incriminates abnormalities within the central nervous system (CNS). However, peripheral neuropathy is classically listed as a risk factor for RLS. This discrepancy is difficult to reconcile. If there truly is a connection between neuropathy and RLS, it has important implications for the screening and treatment of RLS, and it challenges our current concepts of RLS as a predominantly CNS disease.

The proposed association between RLS and peripheral neuropathy is based upon case reports, conflicting case–control studies, and findings from pathological studies. Prevalence estimates of RLS among peripheral neuropathy patients range from 5.2% to 37%. Initial reports found increased prevalence of RLS in patients with acquired neuropathy, but recently a large blinded case–control study did not confirm these results. Furthermore, in this recent study, neuropathy subjects often endorsed RLS-like symptoms, which could not be confirmed on diagnostic evaluation, suggesting that  symptom overlap between RLS and neuropathic pain may be a common confound. This study also showed an increased prevalence of RLS selectively among hereditary neuropathy patients, which raises questions about the genetic relationship between RLS and neuropathy. Small pathologic studies have detected features of subclinical sensory neuropathy in some RLS patients. If confirmed, these findings may suggest the existence of a separate subclinical neuropathy/RLS syndrome, the nature of which must be further delineated.

Keywords: restless legs syndrome, peripheral neuropathy, prevalence, review, genetics

Correspondence: Dr Ronald B. Postuma, Division of Neurology, L7-305 Montreal General Hospital, 1650 Cedar Ave., Montreal, Quebec, Canada H3G 1A4. Tel: +1-514-934-8058; fax: +1-514-934-8265; e-mail: ron.postuma@mcgill.ca

Orthostatic Headache with and without Cerebrospinal Fluid Leak: A Review

Andrea N. Leep Hunderfund and Bahram Mokri. Orthostatic Headache with and without CSF Leak. The European Neurological Journal., September 2009; 1(1): 57-58

Andrea N. Leep Hunderfund and Bahram Mokri

Affiliation: Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN, USA

Submission date: 20th June 2009, Revision date: 8th August 2009, Acceptance date: 17th August 2009


ABSTRACT

Orthostatic headache is a well-known complication of traumatic or iatrogenic dural puncture as well as overdraining ventricular shunts for hydrocephalus. Orthostatic headache that starts spontaneously is most often due to spontaneous cerebrospinal fluid (CSF) leak, but can also occur in the absence of CSF leak. The purpose of this article is to provide a review of the causes, clinical characteristics, pathophysiologic mechanisms, evaluation, and management of orthostatic headache with and without CSF leak. MEDLINE and PubMed searches were used to identify pertinent  articles.

Keywords: headache, orthostatic headache, intracranial hypotension, cerebrospinal fluid leak, postural tachycardia syndrome (POTS)

Correspondence: Bahram Mokri, Mayo Clinic, Neurology, 200 First Street SW, Rochester, MN 55905, USA. Tel: +1-507-284-4036; fax: +1-507-284-4074; e-mail: bmokri@mayo.edu

Incidence and Lifetime Risk of Parkinson’s Disease in Advanced Age: Review and Estimates from the United States

Jane A. Driver and Tobias Kurth. Incidence and Lifetime Risk of Parkinson’s Disease in Advanced Age: Review and Estimates from the United States. The European Neurological Journal., September 2009; 1(1): 19-24


Jane A. Driver¹ and Tobias Kurth²

Affiliations: ¹Divisions of Aging and ²Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; ³Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA; ⁴INSERM Unit 708—Neuroepidemiology, Paris, France; ⁵Faculty of Medicine, Pierre et Marie Curie University, Paris, France

Submission date: 27th June 2009, Revision date: 15th July 2009, Acceptance date: 5th August 2009


ABSTRACT
Age is the strongest known risk factor for Parkinson’s disease (PD). However, its incidence after the age of 80 years is controversial. We examined existing data on the incidence of PD in advanced age, with a focus on studies from the United States. The evidence suggests that PD incidence in men continues to increase in an age-dependent fashion after age 80 years, at least until age 90 years. Data in women are insufficient to draw any conclusions.

Lifetime risk is a helpful way of summarizing the absolute risk of ever developing a disease during one’s remaining lifetime. It reflects the true risk of disease in an elderly population because it adjusts for competing risks of death. We discuss the utility of the lifetime risk statistic and present data from the Physicians’ Health Study. In this cohort of initially healthy and longlived men, the lifetime risk of PD at age 45 years was 1 in 15, higher than the risk of lung, colorectal, and bladder cancer. While the remaining lifetime risk of PD declined slightly with increasing age, it remained substantial at age 80 years, with a risk of 1 in 21. As life expectancy continues to increase worldwide, the burden of PD will grow dramatically. More estimates of the lifetime risk of PD in general populations are needed.

Keywords: Parkinson’s disease, incidence, lifetime risk, cohort study, review

Correspondence: Jane A. Driver, Division of Aging, Brigham and Women’s Hospital, 1620 Tremont Street, Boston, MA 02120, USA. Tel: +1-617-525-7946; fax: +1-617-525-7739; e-mail: jdriver@partners.org

Imaging in Familial Frontotemporal Lobar Degeneration With Mutations in MAPT or PGRN

Jennifer L. Whitwell and Keith A. Josephs. Imaging in Familial Frontotemporal Lobar Degeneration with Mutations in MAPT or PGRN. The European Neurological Journal., September 2009; 1(1): 25-32

Jennifer L. Whitwell and Keith A. Josephs

Affiliations: Departments of 1Radiology and 2Neurology, Mayo Clinic, Rochester, MN, USA

Submission date: 29th May 2009, Revision date: 11th July 2009, Acceptance date: 8th August 2009


ABSTRACT
Background:
Familial frontotemporal lobar degeneration is most commonly related to mutations in the microtubule associated protein tau (MAPT) gene or the progranulin (PGRN) gene.

Methods:
Review of imaging findings in subjects with MAPT and PGRN mutations.

Results:
Patterns of atrophy vary across subjects yet patterns of anterior temporal dominant atrophy appear to be associated with MAPT mutations, while parietal lobe atrophy and significant asymmetry appear to be associated with PGRN
mutations.

Conclusions:
Imaging may be helpful in differentiating familial frontotemporal dementia patients with mutations in MAPT from those with mutations in PGRN.

Keywords: frontotemporal lobar degeneration, tau, progranulin, structural imaging, functional imaging, voxel-based morphometry, genetic

Correspondence: Keith A. Josephs, MST, MD, MS, Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Tel: +1-507-538-1038; fax: +1-507-538-6012; e-mail: josephs.keith@mayo.edu