European Neurological Journal Vol II Issue 2

Muscle Testing in the Diagnosis of Work-Related Upper Limb Complaints

Jørgen Riis Jepsen¹ and Carl-Göran Hagert²

Affiliations: ¹Centre of Maritime Health and Safety, University of Southern Denmark, Esbjerg, Denmark and ²Department of Orthopedic Surgery, University Hospital, Lund, Sweden

Correspondence: Jørgen Riis Jepsen, Centre of Maritime Health and Safety, University of Southern Denmark, Niels Bohrs Vej 9–10, Sydvestjysk Sygehus, Østergade 81–83, DK-6700 Esbjerg, Denmark; Tel: +45-65504264; Fax: +45-79182294; e-mail: jriis@cmss.sdu.dk; joergen.riis.jepsen@svs.regionsyddanmark.dk

ABSTRACT

Patients with work-related upper limb conditions frequently present a triad of neuropathic symptoms like pain, weakness, and numbness/tingling that suggests involvement of the peripheral nerves. Consequently, the physical examination must be able to identify or rule out an impaired function of these. Here we propose an examination technique based on a recognized classical paradigm, namely that impaired function of a peripheral nerve leads to reduced strength of the muscles it innervates. We have previously validated an extensive physical examination of the upper limb nerves and found that it enabled us to accurately identify and locate nerve afflictions in a high proportion of patients and occupationally exposed subjects. This relatively extensive approach may be regarded as complicated and time consuming. Therefore, we review the technique and interpretation of an easy and rapid assessment of three antagonist muscle pairs (Pectoral—Posterior deltoid, Biceps—Triceps, Flexor carpi radialis—Extensor carpi radialis brevis) and three additional individual muscles (Extensor carpi ulnaris, Abductor pollicis brevis, Abductor digiti minimi). This examination enables clinicians to identify patterns of weakness in accordance with specific locations of peripheral nerve afflictions. These patterns are present in a major proportion of work-related upper limb disorders, including the so-called “non-specific” disorders that are currently uncovered by diagnostic criteria because a conventional physical examination cannot demonstrate physical abnormalities. We propose testing of these nine muscles to be routinely integrated in the physical upper limb examination.

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

Reducing the Risk of Stroke in Type 2 Diabetes: A Critical Review

REVIEW ARTICLE


Dirk Sander^1,2, Thorleif Etgen^3,4, Holger Poppert² and Kerstin Sander^1,2

Affiliations: ¹Department of Neurology, Medical Park Hospital and ²Department of Neurology, Technische Universität München and ³Department of Neurology,Klinikum Traunstein, Germany and ⁴Department of Psychiatry and Psychotherapy, Technische Universität München, Germany

ABSTRACT

Stroke is the second most frequent cause of death worldwide and the most frequent cause of permanent disability. Patients with diabetes mellitus (Dm) are at 1.5–3 times the risk of stroke compared with the general population. Cerebrovascular disease causes 20% of deaths in diabetic patients. Interestingly, there are some striking differences of stroke patterns between diabetic and nondiabetic subjects suffering a stroke. An ideal treatment of Dm is of enormous concern because of its significance as a risk factor for emerging atherosclerotic diseases such as stroke, as well as in acute stroke, owing to its relevance for the clinical outcome. Intensified blood glucose-lowering regimens using intravenous insulin are currently being replaced by a more liberal therapy on the Stroke unit. Overall, there is a need for rigorous evaluations of new therapeutic approaches in both primary and secondary prevention of stroke and management of acute stroke in patients with type 2 diabetes. Recent data demonstrate that there is no optimum of a target HbA1c that fits for all patients. Instead we will need an individualized therapy taking into account age, comorbidity, duration of diabetes, and side effects of drugs. This review summarizes the evidence regarding current therapeutic interventions and their impact on the risk of stroke in subjects with type 2 diabetes, and highlights potential strategies for improving outcomes.

Keywords: stroke, diabetes mellitus, epidemiology, risk factors, treatment, sex differences

Correspondence: Prof Dr Dirk Sander, Department of Neurology, Medical Park Hospital, Thanngasse 15 83483 Bischofswiesen, Germany. Tel:+49-8652-89517; Fax: +49-8652-89271; e-mail: D.Sander@mac.com

L-dopa-Induced Dyskinesias in Parkinson's Disease

REVIEW ARTICLE


Iciar Aviles-Olmos*, Raul Martinez-Fernandez*, and Thomas Foltynie

Affiliation: Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London,United Kingdom

ABSTRACT

Levodopa (L-dopa) is the most effective treatment for the relief of the motor symptoms of Parkinson's disease (PD). Its use is limited by the development of drug-induced involuntary movements known as dyskinesias, which can appear in approximately 40% of the PD patients after 5 years of treatment. In recent years we have learned a great deal about the processes involved in the appearance of L-dopa-induced dyskinesia (LID). Non-physiological pulsatile stimulation of dopamine receptors that occurs as a consequence of the use of short-lasting drugs, dysfunctional dopamine release, and abnormal postsynaptic dopamine receptor internalization together with disrupted synaptic plasticity all appear to have direct effects on LID development. Avoiding or delaying dyskinesia development and treating patients in this “advanced” stage of PD is a challenge and requires considerable expertise and individualization of therapy. The aim of this review is to outline the clinical phenomenology of LID, describe an overview of what is known about their pathophysiology, and provide guidance in the range of therapeutic approaches that can be tailored to the individual patient.

Keywords: levodopa-induced dyskinesia (LID), Parkinson’s disease (PD), synaptic plasticity, dysfunctional dopamine release, dopamine receptor supersensitivity

Correspondence: Iciar Aviles-Olmos, Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement
Disorders, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, United Kingdom. Tel: +44-08451555000 Ext. 18739; e-mail:
i.olmos@ion.ucl.ac.uk

Familial Adolescent-Onset Scoliosis and Segmental Dystonia

REVIEW ARTICLE

David Bradley, Sean O’Riordan and Michael Hutchinson

Affiliation : Department of Neurology, St. Vincent’s University Hospital, Dublin, Ireland

ABSTRACT

Idiopathic scoliosis is a common disorder characterized by abnormal curvature of the spine with onset typically in adolescence. Adult-onset primary torsion dystonia (AOPTD) is a focal dystonia with onset in early-middle age consisting of abnormal twisting or directional movements and postures; common phenotypes include cervical dystonia, blepharospasm, and focal hand dystonia. Numerous case reports and case–control studies indicate an association between childhood and adolescent-onset scoliosis and the subsequent development of adult-onset focal dystonia, most commonly cervical or segmental dystonia. In this review we examine the literature linking these two disorders and consider the pathophysiology of their association.
 

Keywords: adult-onset primary torsion dystonia (AOPTD), segmental dystonia, cervical dystonia, idiopathic scoliosis

Correspondence: David Bradley (or Prof Michael Hutchinson), Department of Neurology, St. Vincent’s University Hospital, Elm Park, Dublin 4, Ireland. Tel: +35312774179; Fax: +35312773506; e-mail: david.bradley@ucd.ie (or mhutchin@iol.ie)

Third-Generation Antiepileptic Drugs for Treating Partial-Onset Seizures

REVIEW ARTICLE


Gregory L Krauss, Joyce Choi and Tung Tran

Affiliation: Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA

ABSTRACT

Several new “third-generation” antiepileptic drugs (AEDs)—lacosamide, eslicarbazepine acetate, and retigabine—have been developed that may benefit patients with drug-resistant partial-onset seizures. We review the efficacy, tolerability, safety, and pharmacology of these new AEDs and compare these with previous AEDs used to treat partial-onset epilepsy. At optimal doses, the new AEDs benefit approximately 40% of patients with drug-resistant epilepsy, with few major safety concerns. Tolerability for the AEDs varied markedly across their dose ranges, with dizziness and other central nervous system (CNS)-related adverse events occurring relatively often at high doses when given in polytherapy. Studies are needed to directly compare the effectiveness of the three new and previous AEDs, and to determine the tolerability of new AEDs in patients whose concomitant AEDs are reduced. These “third-generation” AEDs provide potential new treatment options for patients failing treatment with previous AEDs.

Keywords: antiepilepsy drugs, anticonvulsants, epilepsy, eslicarbazepine, retigabine, lacosamide
Correspondence: Gregory L Krauss, Meyer 2-147, 600 N Wolfe St., Baltimore, MD 21287, USA. Tel: (1)-410-955-2822; Fax: (1)-410-955-0751;e-mail: gkrauss@Djhmi.edu

The Endogenous Nitric Oxide Synthase Inhibitor ADMA and Cerebrovascular Disease

REVIEW ARTICLE


Fabian Muller¹, Rainer H Boger², Sudha Seshadri^3,4 and Renke Maas¹

Affiliations: ¹Institute of Experimental and Clinical Pharmacology and Toxicology, University Erlangen-Nuremberg, Erlangen, Germany; ²Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; ³The National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, MA, USA and ⁴Department of Neurology, School of Medicine, Boston University, Boston, MA, USA

ABSTRACT

This review gives an overview of currently available data from clinical studies relating the endogenous nitric oxide (NO) synthase inhibitor asymmetrical dimethylarginine (ADMA) to cerebrovascular disease. In the majority of studies, ADMA plasma concentration correlates positively with the intima media thickness of the carotid artery. Moreover, elevation of plasma ADMA predicts prevalent cerebrovascular disease, progression of atherosclerosis, and adverse clinical outcome. Data from in vitro experiments and infusion studies in mice and men suggest that inhibition of NO synthesis by ADMA is a plausible pathomechanism behind these clinical findings. However, ADMA plasma concentrations associated with discernible differences in atherosclerotic burden in population‐based studies are substantially lower than ADMA concentrations required to elicit functional effects in vitro. A further investigation of the metabolism and distribution of ADMA in vivo may help to resolve these issues.

Keywords: Asymmetric dimethylarginine, ADMA, Carotid artery, Intima‐media thickness, Atherosclerosis, Nitric oxide synthase
Correspondence: R Maas, Institute of Experimental and Clinical Pharmacology and Toxicology, University Erlangen‐Nuremberg, Fahrstrasse 17, 91054 Erlangen, Germany. Tel: (49)‐9131‐85‐22754; Fax: (49)‐9131‐85‐22773; e‐mail: renke.maas@pharmakologie.uni‐erlangen.de

Long‐Term Clinical and Neurophysiological Follow‐Up of Familial Amyloid Polyneuropathy Patients after Liver Transplantation: Comparison between Two Historical Different Groups of Patients

REVIEW ARTICLE


Isabel M Conceicao, Jose´ F Castro and Mamede de Carvalho

Affiliation: Department of Neurosciences, Hospital de Santa Maria, Neuromuscular Unit, Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Portugal

ABSTRACT

We tested if patients with familial amyloid polyneuropathy (FAP) type I have had a better outcome after liver transplantation (LT) in recent years. We compared two identical groups of patients: group I, 14 patients who underwent LT between 1993 and 2002; group II, 19 patients submitted to LT between 2003 and 2007. We found no statistically significant difference in clinical and neurophysiological progression between the two groups after LT; nerve function did not improve. Novel treatments are necessary.

Keywords: electromyography, familial amyloid polyneuropathy, liver transplantation, nerve conduction studies
Correspondence: Isabel Conceição, Department of Neurology, Hospital de Santa Maria, Av Prof Egas Moniz, 1649‐028 Lisbon, Portugal. Tel/Fax: (35)‐1‐21‐7805219; e‐mail: imsconceicao@gmail.com

Prevalence and Clinical Features of LRRK2 Mutations in Patients with Parkinson Disease

Review Article


Pilar Gómez‐Garre ¹, Fátima Carrillo ¹ and Pablo Mir ^{1 2}

Affiliations: ¹Unidad de Trastornos del Movimiento, Servicio de Neurologıa y Neurofisiologıa Clınica, Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocıo/CSIC/Universidad de Sevilla, Seville, Spain and ²Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain


ABSTRACT

In recent years, 16 PARK loci have been reported to be associated with Parkinson disease (PD). The genes in nine of these PARK loci have already been identified. To date, mutations in LRRK2 (PARK8) are the most common genetic determinant of PD identified. These mutations are common in both early‐ and late‐onset PD, occurring in familial and idiopathic PD patients with a variable frequency among ethnic backgrounds. LRRK2 is a large gene, with 51 exons, encoding a multidomain protein. The most frequent mutation described is p.G2019S (c.6055G>A). This mutation is located in the kinase domain of the protein and has been observed in familial and idiopathic PD cases. The second most frequent mutation is p.R1441C (c.4321C>T), which has been identified in several populations. Therefore, the positions c.4321 and c.6055 in LRRK2 seem to represent mutational hotspots, although their relative prevalence is determined by ethnicity. Data suggest that the high prevalence of these mutations is a consequence of both founder effect and recurrence. On the other hand, two common non‐synonymous variations within LRRK2 and specific to Asian populations, p.G2385R and p.R1628P, have been found to represent genetic risk factors for the disease. Mean age at PD onset for all LRRK2 mutation carriers is 58.1±14 years. There is no obvious male or female preponderance. Although the onset of LRRK2‐associated PD occurs at a slightly younger age than idiopathic PD, this lacks significant clinical relevance. Clinically affected and some unaffected LRRK2 mutation carriers show a neurochemical profile of dopaminergic dysfunction, as assessed by positron emission tomography (PET), indistinguishable from that of idiopathic PD.

Keywords: Parkinson disease, mutation, neurodegenerative, LRRK2, prevalence, Dardarin
Correspondence: Pablo Mir, Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología, Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot s/n, 41013 Sevilla, Spain. Tel: (+34)‐955012593; Fax: (+34)‐955012597; e‐mail: pablo.mir.sspa@juntadeandalucia.es

Memantine in the Treatment of Neurological Diseases: Lessons from Multiple Sclerosis

Review Article


Gonzalo Arrondo ¹, Manuel Alegre ¹ and Pablo Villoslada ²

Affiliations: ¹Department of Neurosciences, CIMA— University of Navarra, Navarra, Spain and ²Department of Neurosciences, Institute for Biomedical Research August Pi Sunyer—Hospital Clinic of Barcelona, Barcelona, Spain

ABSTRACT

Memantine, an uncompetitive, low‐affinity N‐methyl‐D‐aspartate (NMDA) receptor antagonist, is an approved compound for use in moderate to severe Alzheimer’s disease. Its pharmacological features allow it to block excessive neuronal activation produced by glutamate, while permitting normal activation of the NMDA receptor channel. A review of the trials that have evaluated the use of the compound in vascular dementia, Alzheimer’s disease, or both shows that it is well tolerated and has mild but statistically significant positive effects on cognition and other domains of patients with advanced Alzheimer’s disease. Recently, a double‐blind, placebo‐controlled trial in patients with multiple sclerosis reported neurological worsening in several patients similar to the typical pseudoexacerbations of this disease. Also, the use of memantine in patients with Lewy body disease produces adverse effects. Although the mechanisms of such side‐effects are unknown, we suggest that they could be due to the impairment of synaptic transmission in the demyelinated pathways.

Keywords: Memantine, multiple sclerosis, Alzheimer’s disease, Lewy bodies dementia, clinical trial, block conduction, pseudoexacerbations, side‐effects
Correspondence: Pablo Villoslada, Department of Neurology, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain. e‐mail: pvilloslada@clinic.ub.es

Glutamate as a Marker of Infarct Growth in Acute Ischemic Stroke

Implementation and Evaluation of Existing Guidelines on the Use of Neurophysiological Tests in Non‐Acute Migraine Patients

Impulsive‐Compulsive Behaviors and Subthalamic Nucleus Deep Brain Stimulation in Parkinson’s Disease: Review of the Literature

REVIEW ARTICLE

Shen‐Yang Lim ^{1 3}, Mateusz Zuroswski ² and Elena Moro ³
Affiliations: Department of Psychiatry and ² Movement Disorders Center, Division of Neurology, Toronto Western Hospital, University of Toronto ³ , University Health Network,Toronto, Canada

ABSTRACT

Impulsive–compulsive behaviors have been increasingly recognized in patients with Parkinson’s disease (PD). Some authors have proposed that subthalamic nucleus deep brain stimulation (STN DBS) may be a useful treatment for these disorders, but the results of other studies suggest caution. We conducted a review of published cases reporting on a relationship between impulsive–compulsive behaviors and STN DBS in PD. Cases were classified as “good outcome” (i.e., impulsive–compulsive behaviors improved or resolved post‐DBS) or “poor outcome” (no improvement, worsening, or a new development post‐DBS). Seventy‐eight cases of PD patients who underwent STN DBS and exhibited impulsive–compulsive behaviors pre‐ and/or post‐DBS were identified from 25 studies. Patients were more commonly male, had younger onset of PD, and many had a history of substance abuse. Overall, 50.7% experienced a good outcome (61% of cases with dopamine dysregulation syndrome, 35% of cases with impulse control disorders). Predictive factors may include age, gender, neuropsychiatric comorbidities, adherence to treatment, surgical factors (including target selection and electrode location), medical management (including medication and stimulation), and psychosocial factors. However, studies that have been reported to date have generally involved small sample sizes, and most have other significant limitations such as retrospective analysis and lack of detailed case description. Larger, prospective, and systematic studies formally assessing these disorders are required.

Keywords: impulse control disorders, dopamine dysregulation syndrome, punding, impulsive and compulsive behaviors, deep brain stimulation, subthalamic nucleus
Correspondence: Elena Moro, Movement Disorders Center (McL 7-402), Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada. Tel: (1)-416-603-5479; Fax: (1)-416-603-5004; e-mail: elena.moro@uhn.on.ca

The Role of Flow‐Mediated Dilation in Ischemic Stroke: Time for Action

Review Article

Diego Santos-Garcıa^1,2, Miguel Blanco² and Jose Castillo²
Affiliations: ¹Section of Neurology, Hospital A Marcide, Ferrol, Spain and ²Department of Neurology, Hospital Clı´nico Universitario, University of Santiago de Compostela, Santiago de Compostela, Spain

ABSTRACT

Brachial artery flow‐mediated dilation (FMD) is a validated, non‐ invasive physiological measure widely used as a research tool to quantify endothelial function, as pointed out in the study by Calermajer, et al.  According to Moens, et al, FMD is diminished in patients with several coronary risk factors, is an independent predictor of cardiovascular events, and improves with risk reduction therapy. Thus, there are numerous studies on FMD and cardiovascular disease, vascular risk factors, or endothelial dysfunction therapy. In contrast, the usefulness of FMD in ischemic stroke is little known and has been poorly studied. However, FMD could also be of great usefulness in ischemic stroke such as stroke subtype classification, prognostic significance in acute phase, and independent predictor for new‐onset vascular event after first‐ever stroke. In this review article, brachial artery FMD and its role in ischemic stroke is discussed extensively.

Keywords: brachial artery, cardiovascular disease, endothelial dysfunction, flow-mediated dilation, ischemic stroke, nitric oxide
Correspondence: Diego Santos Garcı´a, Section of Neurology, Hospital A Marcide, C/ San Pedro Leixa s/n, 15405 Ferrol, Spain. Tel: (34)-981-334000; Fax: (34)-981-334015; e-mail: diegosangar@yahoo.es

Hemicraniectomy in Tumefactive Demyelinating Disease