Featured Articles from the European Neurological Journal

Pharmacological Management of Central Neuropathic Pain

ABSTRACT

Central neuropathic pain (central pain) may be a serious consequence of injuries or diseases affecting the central nervous system, occurring in up to 50% of patients following spinal cord injury, 25% with multiple sclerosis, and 10% following stroke. Central pain should be suspected if the pain: (1) arises at or within months following a lesion in the central nervous system with no other obvious cause, (2) is distributed within an area of sensory abnormality corresponding to the lesion, (3) is diffuse, (4) is described in terms such as burning, freezing, pins and needles, shooting, or squeezing, or (5) is unrelated to movements or specific positions of the pain-affected area. It is important to exclude nociceptive types of pain for which there may be a curative treatment. Randomized controlled trials support a pharmacological treatment similar to that used in peripheral neuropathic pain. Tricyclic antidepressants, pregabalin, and gabapentin are usually recommended as first-line treatment for central pain, while serotonin–noradrenaline reuptake inhibitors may be used if tricyclic antidepressants are contraindicated. Tramadol and opioids may be used as second-line treatment or escape medication. Central pain patients may be particularly prone to side effects, and an individual treatment approach is necessary.

Strengths and Limitations of Systematic Reviews of Drug Trials: The Biostatistical Perspective

Some thousands of randomized controlled trials are published each year. But clinicians are pinched for time to study the literature. Hence, systematic reviews are important to combine the results for a specific medical question. Meta-analysis is only a statistical method that was used in systematic reviews to combine the results of individual studies. Our aim is to discuss the strengths and potential pitfalls of systematic reviews on the basis of five examples from the literature. We focus on aspects limiting the strength of systematic reviews, such as publication bias, imputation of missing data, and the use of inappropriate statistical methods. Although systematic reviews are key to summarizing evidence, meta-analyses of drug trials should be read with a healthy portion of scepticism.

Topiramate in Migraine Prophylaxis

Review Article

Mark Obermann , Steffen Naegel, Charly Gaul, and Hans-Christoph Diener

Affiliation : Department of Neurology and Headache Center, University of Duisburg-Essen, Essen, Germany

ABSTRACT

The prevalence of migraine in the global adult population is approximately 10%. Migraine has a serious socioeconomic impact on society in general and is associated with considerable medical disability for individual patients. Migraine is characterized by the combination of typical headache with associated autonomic symptoms and/or the presence of aura. Within the past years, considerable advances were made in understanding the pathophysiology of migraine. This has led to improved treatment options for the acute migraine attack as well as migraine prophylaxis. Topiramate is an antiepileptic drug (AED) with a complex mode of action, which has proven its efficacy and safety in the prophylactic treatment of episodic migraine in a number of randomized controlled clinical trials. Topiramate is also effective in treating patients with chronic migraine with and without medication overuse headache. In clinical trials, it was generally considered to be well tolerated by patients, but in everyday clinical practice, side effects can be therapy-limiting in some patients. Treatment benefits and potential adverse events have to be considered carefully for each individual patient to assure optimal treatment success with topiramate. This is a revised and updated version of a previous review by Naegel and Obermann (2010).


Keywords: topiramate, migraine, migraine prophylaxis, chronic migraine, migraine treatment

Correspondence: Mark Obermann, Department of Neurology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
Tel: (+49)-201-723-84385; Fax: (+49)-201-723-5542; e-mail: mark.obermann@uni-due.de

Recent Developments in the Management of Posttraumatic Neuropathic Pain

Review Article

Kurien Koshy and Cory Toth

Affiliation : Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada

ABSTRACT

Injury to the nervous system may lead to posttraumatic neuropathic pain (NeP), an often refractory condition associated with pain, sensory disturbance, and potential weakness and autonomic dysfunction (such as with complex regional pain syndrome). In addition, NeP is often associated with insomnia, difficulties with mood or anxiety, and impaired quality of life. This review will review the causes and nature of NeP with a discussion on the recent breakthroughs in understanding its pathophysiology. Management of this condition is often difficult and requires a multidisciplinary approach consisting of both pharmacological and nonpharmacological treatment. Recent studies identifying gabapentinoids as effective in posttraumatic forms of NeP will be reviewed. Posttraumatic NeP is a complicated and complex disease process that requires ongoing research to understand and manage the needs of its patient population.

Keywords: neuropathic pain, posttraumatic neuropathic pain, complex regional pain syndrome, neuropathy, pharmacotherapy, pregabalin,antidepressants

Correspondence: Cory Toth, Department of Clinical Neurosciences, University of Calgary, HMRB Room 155, 3330 Hospital Drive NW,
Calgary, Alberta, Canada T2N 4N1. Tel: +1-(403)-220-8831; Fax: +1-(403)-283-8731; e-mail: corytoth@shaw.ca

Differential Diagnosis of Longitudinally Extensive Transverse Myelitis in Adults

Review Article


Christopher Eckstein, Stephanie Syc and Shiv Saidha

Affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

ABSTRACT

Longitudinally extensive transverse myelitis (LETM), characterized by spinal cord inflammation extending three or more vertebral segments in length, may be caused by a multitude of disorders. LETM is most commonly associated with neuromyelitis optica (NMO). Such is the frequent association between these two entities that there is a growing tendency amongst physicians to regard them as being practically synonymous with each other. The objective of this review is to highlight the wide range of disorders that may cause LETM and to emphasize the need to carefully consider all potential etiologies in the assessment of LETM. In particular, we focus on the salient clinical, laboratory, and radiographic features of these various disorders, which help them to be differentiated from one another.

Keywords: Longitudinally Extensive Transverse Myelitis, LETM, NMO, neuromyelitis optica, myelopathy

Correspondence: Dr Shiv Saidha, Department of Neurology, Johns Hopkins University School of Medicine, Pathology 627, 600 North Wolfe Street, Baltimore, MD 21287, USA. Tel: +1-4106141653; Fax: +1-4105026736; e-mail: ssaidha2@jhmi.edu

Clinical Data on the Prolonged Release Formulation of Ropinirole

Review Article

Wolfgang H. Jost¹ and Lars Bergmann²

Affiliations: ¹Deutsche Klinik für Diagnostik, Wiesbaden and ²GlaxoSmithKline GmbH, Munich, Germany

ABSTRACT

In the treatment of Parkinson's disease (PD), non-ergoline dopamine agonists are considered the first-choice therapy. Ropinirole has been an internationally established therapy used to treat the signs and symptoms of idiopathic PD for more than 10 years. Because of its moderate elimination half-life, the immediate release (IR) formulation is administered three times daily. Now a prolonged release (PR) form is available, and despite administration once-daily in the morning, plasma level fluctuations are reduced over 24 hours, versus IR, allowing for symptomatic treatment during day and night time with once-daily dosing. The PR formulation can be up-titrated more rapidly and simply, reaching clinical efficacy as early as the second week of therapy. In clinical studies, higher doses of ropinirole were achieved with the PR formulation compared with the IR formulation. The results of a randomized double-blind head-to-head study of both formulations in patients with advanced PD demonstrated significantly greater efficacy and a larger l-dopa dose reduction. A positive effect on nighttime motor symptoms and quality of sleep has already been established. Because of once-daily administration, compliance and adherence may also be improved.

Keywords: ropinirole, Parkinson’s disease, dopamine agonist, prolonged release

Correspondence: Prof. Dr.Wolfgang Jost, Deutsche Klinik für Diagnostik, Aukammallee 33, 65191 Wiesbaden/Germany. Tel: 0049-611-577430;Fax: 0049-611-577311; e-mail: jost.neuro@dkd-wiesbaden.de

Neurological Manifestations of Celiac Disease in Children and Adults

Review Article

Aaron Lerner^1, Badira F. Makhoul² and Rami Eliakim³

Affiliation : ¹Pediatric Gastroenterology and nutrition Unit, Carmel Medical Center and ²Department of Gastroenterology, Rambam Health Care Campus and ^1,2Bruce Rappaport School of Medicine, Technion-Israel institute of Technology, Haifa, Israel

ABSTRACT

Celiac disease (CD) is a common, life-long, autoimmune condition, affecting the small intestine of genetically susceptible individuals. The classical clinical picture is disappearing as awareness progresses and the extra-intestinal presentation is emerging. Skin, endocrine, hepatic, skeletal, hematological, gynecological, infertility, dental, and behavioral abnormalities are emerging. Among the new growing domains is the extra-intestinal presentation of CD affecting the peripheral and central neurological systems. This review highlights neurological presentations in these patients, focusing on the clinical signs/symptoms in the pediatric and the adult age group, separately.

Keywords: Celiac disease, neurology, children, adults

Correspondence: Rami Eliakim, Department of Gastroenterology, Rambam Health Care Campus, Bat Galim, Haifa, Israel, 31096. Tel: +972-4-854-3784; Fax: +972-4-854-3058; e-mail: r_eliakim@rambam.health.gov.il

Significance of Perihematomal Edema in Acute Intracerebral Hemorrhage

REVIEW ARTICLE

Jade W Wei, Hisatomi Arima and Craig S Anderson

Affiliation : The George Institute for Global Health and Department of Neurology, Royal Prince Alfred Hospital and University of Sydney, Sydney, Australia

ABSTRACT

Intracerebral hemorrhage (ICH) is the most serious form of stroke, with more than two-thirds of the patients either dying or left permanently disabled from the condition. Despite considerable research effort, there is still no treatment of proven efficacy for ICH and the chances of surviving an ICH has failed to improve in recent decades. The brain damage from the initial hematoma is considered largely irreversible, which is because of the early time window of opportunity for treatment benefit and the modest potential effects of any medical therapy that limits hematoma growth. Knowledge has accumulated regarding the nature of secondary effects of the perihematomal edema in ICH, making it an attractive therapeutic target. The pathophysiology of ICH-related perihematomal edema is complex: a number of different mechanisms are involved from the initial hydrostatic pressure of the hematoma to the subsequent toxic effects of breakdown products resulting from coagulation cascade activation and erythrocyte lysis as part of the natural process of hematoma resolution. Although perihematomal edema and hematoma volumes are strongly correlated, there is less and conclusive evidence regarding the independent prognostic role of perihematomal edema per se. Patient management is primarily supportive and aimed at reducing resulting increases in intracranial pressure. No therapies have been shown to definitely influence outcome, and all are associated with some hazard. Further studies are required to clarify the relationship between perihematomal edema and outcome in ICH, and to translate the positive results of therapies identified in the laboratory into the clinical domain.

Keywords: perihematomal edema, intracerebral hemorrhage, stroke, treatment

Correspondence: Craig S Anderson, The George Institute for Global Health, P.O. BoxM201,Missenden Rd, Camperdown,NSW2050, Australia.
Tel: +61-2-9993-4521; Fax: +61-2-9993-4502; e-mail: canderson@george.org.au

A Complete Literature Survey: Vitamin D and Multiple Sclerosis – What is Clearly Evident?

REVIEW ARTICLE


Irfan Rafique and Jette Lautrup Frederiksen

Affiliation: Department of Neurology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark

ABSTRACT

An increase in the number of multiple sclerosis (MS) cases is seen with increasing distance from the equator. This has directed attention toward vitamin D, which is synthesized in our skin with the help of sunlight. Thus the following questions are raised: Is the level of serum vitamin D associated to MS? Is there any difference in the risk of MS depending on whether vitamin D is formed by sun exposure or consumed through diet? Is the impact of vitamin D on MS genetically correlated? Is it possible to treat MS with vitamin D? Fifty-two articles found on the Internet by peer-reviewed databases, primarily PubMed, form the basis of this complete literature survey. Eight of nine examinations showed significant connection of low concentrations of vitamin D in the serum and MS. Exposure to sun during both childhood and puberty is of significance to the development of MS, whereas vitamin D consumed in diet is not decisive. The fact that there is coherence between vitamin D receptor gene polymorphism and MS is not unambiguous, since several investigations have showed conflicting results. As a result of limitations in trials we are not able to conclude whether vitamin D should be used as treatment.

Keywords: multiple sclerosis, 25 (OH)D, vitamin D 1,25 (OH)D, vitamin D receptor genes, vitamin supplements, sunlight
Correspondence: Irfan Rafique, Medical Student;. Tel: + 45 43 233 041; Fax: + 45 43 233 92; e-mail: xlz855@alumni.ku.dk