European Neurological Journal Vol II Issue 1

Recent Developments in the Pharmacological Management of Neuropathic Pain

Attal N, Martinez V.  Recent Developments in the Pharmacological Management of Neuropathic Pain.  European Neurological Journal, June 2010; 2(1):  25-30


Review Article

Nadine Attal¹ and Valeria Martinez^1,2

Affiliations: ¹INSERM U987, Centre d’Evaluation et de Traitement de la Douleur, Hopital Ambroise Pare´, APHP, Boulogne-Billancourt, and Universite´ Versailles-Saint-Quentin, Versailles, France and ²Service d’anesthesie reanimation chirurgicale, Hopital Raymond Poincare´, APHP, Garches, France


ABSTRACT

The management of patients with chronic neuropathic pain (NP) is challenging, despite several attempts to develop a more rational therapeutic approach. Most randomized controlled trials (RCTs) of NP have been conducted on postherpetic neuralgia (PHN) and diabetic painful polyneuropathy (PPN). These placebo‐controlled trials mainly studied the effects of individual medications. Outcome measures were generally restricted to the global assessment of pain and the quality of pain was seldom taken into account. However, new studies have recently appeared that may contribute to revising this statement. Several RCTs have been performed on indications that have been neglected thus far, such as central pain, painful radiculopathies, and post‐traumatic NP; combination studies and head‐to‐head comparative studies have appeared, although these are scarce; recent studies have also used a more comprehensive assessment of patients, including pain quality. The present review aims at emphasizing new developments in the therapeutic management of NP, particularly with regard to these new clinical studies. Potential emerging drug treatments will also be described.

Keywords: neuropathic pain, randomized controlled trials, systematic review, emerging treatments
Correspondence: Nadine Attal, INSERM U 987, Centre d'Evaluation et de Traitement de la Douleur, Hôpital Ambroise Paré, APHP, Boulogne‐Billancourt, France. Tel: 0033149095946; Fax: 0033149094435; e‐mail: nadine.attal@apr.aphp.fr

Morbid Anxiety as a Risk Factor in Patients with Somatic Diseases: A Review of Recent Findings

Allgulander C.  Morbid Anxiety as a Risk Factor in Patients with Somatic Diseases:  A Review of Recent Findings.  European Neurological Journal, June 2010; 2(1):  31-39

Review Article


Christer Allgulander

Affiliation: Karolinska Institutet Department of Clinical Neuroscience, Section of Psychiatry, Karolinska University Hospital – Huddinge, Sweden


ABSTRACT

This review focuses on anxiety in patients with somatic diseases, based on studies published from 2007 through January 2010. It covers neurological, cardiovascular, respiratory, and endocrine diseases as well as HIV/AIDS, trauma, skin conditions, and other somatic diseases. Anxiety may be an acute and adequate reaction to receiving a diagnosis of a disabling or life‐threatening disease. It may also be precipitated by stroke, injury, or the distress of having to manage diabetes or AIDS. Several studies show that anxious patients inflate self‐perceived health problems and are more sensitive to physical symptoms in a manner disproportionate to objective disease validators. Therefore, intervention should be reserved for those patients most likely to benefit from reduced anxiety, improved management of the somatic condition, and improved functioning.

This issue is particularly important for the elderly, who represent a growing global challenge. Late‐onset anxiety may be caused by loneliness and bereavement, and can be compounded by immobilization and somatic disease. Controlled treatment studies of anxiolytics as well as their potential benefits in the overall management of anxious patients with somatic disease are generally lacking. Research to determine the benefits and costs of such treatments in primary and tertiary care is currently underway.

Keywords: anxiety disorders, stroke, diabetes, COPD, pain, IBS, SLE
Correspondence: Christer Allgulander , M.D., Associate Professor, Senior Lecturer, Karolinska Institutet, Department of Clinical Neuroscience, Section of Psychiatry, M56 Karolinska University Hospital – Huddinge, SE 141 86 Huddinge, Sweden. e‐mail: Christer.Allgulander@ki.se

Adherence to interferon beta therapies in multiple sclerosis

Portaccio M, Amato M P.  Adherence to Interferon Beta Therapies in Multiple Sclerosis.  European Neurological Journal, June 2010; 2(1):  19-24

Review article


Emilio Portaccio and Maria Pia Amato

Affiliation: Department of Neurology, University of Florence, Florence, Italy


ABSTRACT

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system and the most common cause of neurological disabilities in young adults. Current available disease‐modifying treatments (DMTs) are aimed at reducing the frequency of relapses and delaying the progression of disability. First line DMTs consist of immunomodulatory agents, including interferon beta (IFNB) and glatiramer acetate. All these therapies must be administered chronically and parenterally, and they are variably associated with systemic and injection‐site side effects. With IFNB, a sizable rate of treatment discontinuation has to be expected at the start of therapy. Treatment suspension is often caused by the occurrence of side effects such as flu‐like syndrome and injection‐site reactions. Approaches aimed at reducing the number of subjects discontinuing IFNB encompass both pharmacological and non‐pharmacological interventions and may involve several professionals, including neurologists, psychologists, and nurses. The development of new formulations of IFNB and new injection devices has led to a significant improvement in the tolerability profile and compliance with therapy over time. Promoting adherence to IFNB therapies in MS patients represents a great challenge for neurologists and needs continued attention in the future.

Keywords: multiple sclerosis, interferon beta therapy, adherence
Correspondence: Emilio Portaccio , MD, Department of Neurology, University of Florence, Viale Morgagni, 85, 50134 Florence, Italy. Tel: +39‐055‐7947122; Fax: +39‐055‐7947287; e‐mail: portilio@tin.it

Research Progress in Multiple Sclerosis

Constantinescu C.  Research Progress in Multiple Sclerosis.  European Neurological Journal, June 2010; 2(1):  1

Research Progress

Cris Constantinescu

Affiliation: Division of Clinical Neurology, University of Nottingham, Queen’s Medical Centre, C Floor West Block, Nottingham NG7 2UH, UK

The last two decades have seen a revolution in the understanding and management of multiple sclerosis (MS). The advent of magnetic resonance imaging (MRI), the introduction of the first‐generation of disease‐modifying treatments and more recently the elucidation of key aspects of MS immunogenetics and epidemiology have been essential contributors to this revolution, which no doubt will be reflected in better quality of life and care, and, we hope, a more favorable natural history of MS.

Correspondence: Cris S Constantinescu, MD PhD, Professor, Division of Clinical Neurology, University of Nottingham, Queen’s Medical Centre, C Floor West Block, Nottingham NG7 2UH, UK, Tel: (+44) 115-8754597/98; Fax: (+44) 115-9709738

Multifocal Motor Neuropathy

Dimberg E L.  Multifocal Motor Neuropathy.  European Neurological Journal, June 2010; 2(1):  89-97

Review Article


Elliot L Dimberg

Affiliation: Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA


ABSTRACT

Multifocal motor neuropathy is a progressive, predominantly distal, upper extremity lower motor neuropathy. It is acquired, immune mediated, and commonly associated with antiganglioside antibodies against GM1. The electrophysiological hallmark is conduction block seen in motor but not sensory nerves. It is ultimately a treatable disease with most patients responding to intravenous immunoglobulin, the treatment of choice. It must be differentiated from motor neuron disease, an untreatable disease, and other immune‐mediated neuropathies because corticosteroids and plasma exchange, commonly used in many autoimmune neurological disorders, are ineffective in multifocal motor neuropathy. This review will explore the clinical, electrophysiological, pathological, and treatment issues related to this disease.

Keywords: multifocal motor neuropathy, conduction block, ganglioside, GM1 antibodies, intravenous immunoglobulin, cyclophosphamide
Correspondence: Elliot L Dimberg, , , 4500 San Pablo Road, Jacksonville, FL 32224, USA. Tel: (1)‐904‐953‐2000; Fax: (1)‐904‐953‐0757; e‐mail: Dimberg.Elliot@mayo.edu

Update on Secondary Stroke Prevention

Kirshner H S.  Update on Secondary Stroke Prevention.  European Neurological Journal, June 2010; 2(1):  55-63

Review Article


Howard Kirshner

Affiliation: Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA


ABSTRACT

This is a review of currently recommended measures for the secondary prevention of stroke, along with the evidence basis for the recommendations. They start with lifestyle modifications and risk factor reduction, continue with anticoagulation for atrial fibrillation and related cardiac sources of embolic stroke, and conclude with alternative agents for antiplatelet therapy. Relevant guidelines are cited to support recommendations.

Keywords: stroke, ischemic stroke, risk factors, secondary prevention, antiplatelet therapy
Correspondence: Howard S Kirshner, A‐0118 Medical Center North, Vanderbilt University Medical Center, Nashville, TN 37232‐2551, USA. Tel: (1)‐615‐936‐1354; Fax: (1)‐615‐936‐1286; e‐mail: howard.kirshner@vanderbilt.edu

Patient‐Perceived Retrospective Outcome of Duodenal Levodopa Infusion in Advanced Parkinson’s Disease

Recent Developments in the Management of Post‐Traumatic Pain

Recla J M.  Recent Developments in the Management of Post-Traumatic Pain.  European Neurological Journal, June 2010; 2(1):  73-82

Review Article


Jill M Recla ^{1 2}

Affiliations: ¹IGERT Program in Functional Genomics, Graduate School of Biomedical Sciences, The University of Maine, Orono, Maine, USA and ²The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, USA


ABSTRACT

A variety of analgesic options are currently available for the treatment of acute and chronic post‐traumatic pain (PTP). These include non‐steroidal anti‐inflammatory drugs (NSAIDs), opioids, and adjuvant analgesics (i.e., antidepressants, anticonvulsants, N‐methyl‐D‐aspartate receptor antagonists), as well as muscle relaxants and local anesthetics. Unfavorable safety profiles have limited the use of many of these drugs in PTP management, however, and PTP often remains inadequately treated. Contemporary research has focused on the development of more efficacious pharmaceuticals with fewer associated side‐effects, as well as on the use of non‐pharmaceutical approaches, such as neurofeedback, to facilitate or enhance analgesia. This review discusses these advances in detail, providing an overview of the recent developments in the management of PTP.

Keywords: post‐traumatic pain, non‐steroidal anti‐inflammatory drugs (NSAIDs), opioids, adjuvant analgesics, neurofeedback, electroencephalogram (EEG), pain management
Correspondence: Jill M Recla, , , 600 Main Street, Bar Harbor, ME 04609, USA. Tel: (1)‐207‐288‐6408; e‐mail: jill.recla@jax.org

Exercise‐Induced Hypertension: a Rare Manifestation of Pure Autonomic Failure

Sakakibara R, Ogawa E, Kishi M, Uchiyama T, Yamamoto T. Exercise‐Induced Hypertension: a Rare Manifestation of Pure Autonomic Failure.  European Neurological Journal, June 2010; 2(1):  99-101

Case report


Ryuji Sakakibara ¹, Emina Ogawa ¹, Masahiko Kishi ¹, Tomoyuki Uchiyama 2 and Tatsuya Yamamoto ²

Affiliations: ¹Neurology Division, Department of Internal Medicine, Sakura Medical Center, Toho University, Sakura, Japan and ²Department of Neurology, Chiba University, Chiba, Japan


ABSTRACT

Pure autonomic failure (PAF) is an idiopathic neurodegenerative disorder that presents with clinical symptoms of autonomic dysfunction, but no other neurological deficits. The main structure affected in PAF is the pre‐ and postganglionic sympathetic autonomic neurons, where Lewy body pathology has been documented. Cardinal features of PAF are cardiovascular, urinary, gastrointestinal, and other forms of autonomic nervous system involvement. Among these, cardiovascular dysfunction occurs earlier than bladder dysfunction and becomes a predominant clinical manifestation in PAF, which contrasts with the early genitourinary dysfunction in multiple system atrophy patients. Progression of PAF is usually slow and insidious; therefore, it can be treated conservatively. Whereas postural, postprandial, exercise, and micturition‐induced hypotension are all cardinal features in such patients, recumbent and exercise‐induced hypertension may also occur. Although the exact mechanism of exercise‐induced hypertension remains obscure, the balance of adrenergic receptors, particularly altered alpha1 vasoconstrictor function, might contribute to exercise‐induced hypertension. Recognition of exercise‐induced hypertension is important in order to avoid potential life‐threatening adverse events.

Keywords: pure autonomic failure, exercise, hypertension
Correspondence: Ryuji Sakakibara, Neurology, Internal Medicine, Sakura Medical Center, Toho University, 564‐1 Shimoshizu, Sakura, 285‐8741, Japan. Tel: (81)‐43‐462‐8811, Ext. 2323; Fax: (81)‐43‐487‐4246; e‐mail: sakakibara@sakura.med.toho‐u.ac.jp

Safety of Thrombolysis in Patients with Acute Ischemic Stroke caused by Cervical Artery Dissection—A Review

Zinkstok S M, Nederkoorn P J, Vergouwen M DI.  Safety of Thrombolysis in Patients with Acute Ischemic Stroke Caused by Cervical Artery Disseciton – A Review.  European Neurological Journal, June 2010; 2(1):  65-72

Review article


SM Zinkstok  ¹, PJ Nederkoorn  ¹ and MDI Vergouwen  ²
Affiliations: ¹Department of Neurology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands and ²Division of Neurology, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada


ABSTRACT

Background and purpose. It is unclear whether thrombolysis is safe in patients with dissection‐related ischemic strokes. The purpose of the present study is to review the available literature on this subject.
Methods. We systematically searched the PUBMED and EMBASE databases for all studies and case reports describing thrombolytic treatment in patients with cervical artery dissection (CAD). Studies were assessed on safety, stroke progression, stroke recurrence, and death.
Results. Thirteen retrospective series and 22 case reports comprising 185 patients were identified (intravenous thrombolysis (IVT): n = 144; intra‐arterial thrombolysis (IAT): n = 25; IVT followed by IAT: n = 1; IAT with additional endovascular procedures: n = 15). Complication rates due to IVT were low (intramural hematoma extension 0%, pseudoaneurysm 1.4%, recurrent stroke 1.4%, progressive stroke 0.7%, symptomatic intracranial hemorrhage 3.5%). In patients treated with IAT, either with or without additional interventional procedures, no complications were reported. Mortality was 7% in IVT‐treated patients, 8% in IAT‐treated patients, and 0% in patients who had IAT in combination with other endovascular procedures. Mortality was mostly attributed to initial stroke severity and not to thrombolysis‐related complications.
Conclusion. The results of this review suggest that intravenous thrombolysis in CAD is safe. Currently, there is no evidence to exclude patients suspected of dissection‐related stroke from thrombolytic treatment.

Keywords: ischemic stroke, dissection, thrombolysis, recombinant tissue plasminogen activator (rt‐PA), safety, review
Correspondence: M D I Vergouwen, Division of Neurology, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, 5th Floor West Wing, Room 425, Toronto, Ontario M5T 2S8, Canada. Tel: (1)‐416‐603‐5800, ext. 4468; Fax: (1)‐416‐603‐7733; e‐mail: Mervyn.Vergouwen@uhn.on.ca

Individualized Management of Cervical Dystonia with Different Serotypes of Botulinum Toxin: Recent Therapeutic Advances and Risk of Development of Neutralizing Antibodies

Kamm C, Benecke R.  Individualized Management of Cervical Dystonia with Different Serotypes of Botulinum Toxin:  Recent Therapeutic Advances and Risk of Development of Neutralizing Antibodies.  European Neurological Journal, June 2010; 2(1):  49-54

Review article


Christoph Kamm and Reiner Benecke
Affiliations: Klinik für Neurologie und Poliklinik, Universität Rostock


ABSTRACT

Cervical dystonia is the most frequent form of adult‐onset focal dystonia, characterized by abnormal head and neck posture due to involuntary contractions in a certain set of muscles, sometimes superimposed by tremulous or myoclonic movements. Intramuscular injection of botulinum toxin in carefully selected muscles is nowadays considered the first‐line treatment. For each individual patient, dosage and distribution of muscles to be injected must be accurately selected using experience‐based algorithms, also depending on the formulation of botulinum toxin chosen. This review focuses on recent therapeutic advances in this field, including discussion of recent clinical studies with both serotypes of botulinum toxin (type A and B) that are currently in clinical use. Presently available data indicate that the risk of developing neutralizing antibodies may be higher under therapy with botulinum toxin type B than with type A.

Keywords: cervical dystonia, spasmodic torticollis, botulinum toxin type A, botulinum toxin type B, clinical studies, antibody, secondary non‐responsiveness
Correspondence: Reiner Benecke, Klinik für Neurologie und Poliklinik, Gehlsheimer Str. 20, 18147 Rostock, Germany. Tel: (+49)‐381‐494‐9511; Fax: (+49)‐381‐494‐9512; e‐mail: reiner.benecke@med.uni‐rostock.de

Antidepressants for Migraine Prophylaxis

Lampl C, Schweiger C.  Antidepressants for Migraine Prophylaxis.  European Neurological Journal, June 2010; 2(1):  83-87

Review article


Christian Lampl and Christine Schweiger

Affiliation: Department of Neurology and Pain Medicine, Konventhospital Barmherzige Bru¨der Linz, Linz, Austria


ABSTRACT

The objectives of this review are to provide a comprehensive critical analysis of published reports of randomized controlled trials of antidepressants for reducing headache burden among adults with migraine, and to determine whether efficacy varies according to important patient characteristics, such as coexisting depression. The mechanism whereby amitriptyline and other antidepressants produce their analgesic effects is unknown, but the blockade of serotonin and norepinephrine re‐uptake has been hypothesized to play a pivotal role. Concerning amitriptyline, there is some evidence that this tricyclic antidepressant may be beneficial in the prophylaxis of migraine in some patients. For selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs), beneficial effects are equivalent to those seen in the placebo group within 2 months of therapy. To conclude, there is limited evidence for a clinical superiority of amitriptyline and SSRIs over other treatments with ß‐blockers, anticonvulsants, or calcium channel blockers in preventing migraine. Antidepressants in migraine should be considered if other first‐ or second‐line drugs have not reduced the number of monthly attacks or if concomitant depression exists. Therefore, antidepressants are second‐ or (even) third‐line prophylactic agents in patients with migraine alone.

Keywords: Migraine, antidepressants, prophylactic treatment, SSRIs, SNRIs
Correspondence: Christian Lampl, Department of Neurology and Pain Medicine, Konventhospital Barmherzige Brüder Linz, Seilerstätte 2, Linz, Austria. Tel: (43)‐732‐780‐625320; Fax: (43)‐732‐780‐625398; e‐mail: christian.lampl@bblinz.at

Recent Advances in the Management of Multiple Sclerosis

Pozzilli C, Prosperini L.  Recent Advances in the Management of Multiple Sclerosis.  European Neurological Journal, June 2010; 2(1):  41-48

Review Article

Carlo Pozzilli and Luca Prosperini

Affiliation: Multiple Sclerosis Centre, S. Andrea Hospital, Department of Neurological Sciences, ‘‘La Sapienza’’ University, Rome, Italy

ABSTRACT

Over the last few decades, there have been significant advances in the diagnosis and management of multiple sclerosis (MS), and treatment options for MS have broadened dramatically. The advent of disease‐modifying therapies (DMTs) has changed the clinical and social burden of this disease. First‐line therapies, e.g., interferon beta (IFNB) and glatiramer acetate (GA), are safe, but only partially effective, and in several cases, they are poorly tolerated by patients. Pharmacological and non‐pharmacological interventions, such as nursing support, auto‐injector devices, and patient education programs, may enhance adherence to injected drugs. Comparison studies have demonstrated a substantial equivalence of efficacy between IFNB and GA. Monitoring patient response to first‐line therapies and improving their tolerability represent the primary objectives in the management of treated patients. Second‐line therapies, such as natalizumab or mitoxantrone, are indicated for those patients with breakthrough disease despite first‐line treatment, or with a rapidly evolving course of MS. Safety concerns of second‐line drugs and the lack of long‐term safety data require accurate patient selection and monitoring during treatment. Oral treatments and other monoclonal antibodies will be available in the next few years to improve our armamentarium for the treatment of MS. The present review provides a description of the latest advances in the available therapy for the management of MS and describes the state of promising therapies currently under study.

Keywords: multiple sclerosis, interferon beta, glatiramer acetate, natalizumab, mitoxantrone, oral drugs, monoclonal antibodies
Correspondence: Carlo Pozzilli, Multiple Sclerosis Centre, S. Andrea Hospital, Department of Neurological Sciences, “La Sapienza” University, Via di Grottarossa, 1035, 00189, Rome, Italy. Tel: (39)‐06‐33775686; Fax: (39)‐06‐33775900; e‐mail: carlo.pozzilli@uniroma1.it

Narrative Speech is Impaired in Multiple Sclerosis

Arrondo G, Sepulcre J, Duque B, Toledo J, Villoslada P.  Narrative Speech is Impaired in Multiple Sclerosis.  European Neurological Journal, June 2010; 2(1):  11-18

ORIGINAL ARTICLE


Gonzalo Arrondo ¹, Jorge Sepulcre 1, Beatriz Duque ¹, Jon Toledo ¹ and Pablo Villoslada ^{1 2}
Affiliations: ¹ Department of Neuroscience, Center for Applied Medical Research, University of Navarra and ² Department of Neurology, Hospital Clinic—IDIBAPS

ABSTRACT
Background
Language is frequently impaired in multiple sclerosis (MS) in which, in addition to dysarthria and loss of fluency, other language deficits might affect patients and impinge on their quality of life.

Aims
The aim of this study was to examine spontaneous language production in MS and to assess its relationship with cognitive deterioration.

Methods
Sixteen MS patients and 10 healthy control subjects matched by age and education were studied. Participants were instructed to talk about their life for half an hour. After the transcription of the texts, several parameters were measured, including the number of words, mean and maximum sentence length, lexical density, and number of words produced by the evaluator to maintain conversation. The cognitive impairment of the patients was classified using the Brief Repeatable Battery—Neuropsychology (BRB‐N).

Results
A decrease in the number of words and in sentence length was detected, as well as an increase in the interventions by the neuropsychologist in patients with MS. Patients with cognitive impairment performed worse in most parameters than control subjects and patients with no cognitive impairment. In addition, the number of words spoken by patients and the interventions by the evaluator were correlated with performance in the Paced Auditory Serial Addition Task and phonetic fluency tests of the BRB‐N. Moreover, lexical density was correlated with all cognitive domains.

Conclusions
MS patients have structural problems in language production, and flexibility when constructing a complex discourse is also impaired, with both difficulties being related to cognitive impairment, particularly with executive dysfunction. Cognitive impairment is also related to impoverished lexical access.

Keywords: multiple sclerosis, language, narrative speech, lexical access, cognitive impairment, Brief Repeatable Battery—Neuropsychology
Correspondence: Pablo Villoslada, Department of Neurology, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain. Tel: (+34‐93)4031102; e‐mail: pvilloslada@clinic.ub.es