Intra-operative Imaging Techniques During Surgical Management of Gliomas

c.halagiera — Wed, 02 May 2012 18:35:45 +0000

The goal of glioma surgery is to maximise tumour resection while preventing a new post-operative neurological deficit. For both low- and high-grade gliomas, increased extent of resection correlates with improved progression-free survival as well as with overall survival.^1–5 While some features of brain tumours can be visualised, in general, most aspects of infiltrative gliomas cannot be clearly seen by direct vision, thus making it difficult to evaluate when the resection is complete.

Abstract:

The goal of glioma surgery is to maximise tumour removal while preserving existing function. Intra-operative imaging techniques play an important part in achieving this goal. This article surveys those techniques and discusses the indications, advantages and drawbacks of each. Structural techniques such as intra-operative magnetic resonance imaging (MRI), ultrasound, diffusion tensor imaging and 5-aminolevulinic acid staining offer anatomical information. Functional techniques such as functional MRI, magnetoencephalography and transcranial magnetic stimulation provide information about the functionality of brain regions. When incorporated into a frameless stereotactical neuronavigation system, these modalities increase both the efficacy and safety of glioma surgery by allowing the surgeon to achieve the most extensive and safe resection possible.

Author:

Phiroz E Tarapore

Edward F Chang

Mitchel S Berger

Edition:

European Neurological Review - Volume 7 Issue 1 - Spring 2012

Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis – A Medical, Sociological and Media Controversy

c.halagiera — Wed, 02 May 2012 14:03:07 +0000

Beginning with the publication of a paper by Paolo Zamboni in 2009¹ that claimed an association between a number of cerebral venous ‘abnormalities’ and multiple sclerosis (MS), the international MS community has been embroiled in a debate, unprecedented in scope and controversy.

Abstract:

In 2009, Zamboni et al. coined the term “chronic cerebrospinal venous insufficiency” (CCSVI). On the basis of transcranial and extra-cranial colour-coded Doppler ultrasonography, they operationally defined CCSVI as occurring when at least two out of five “abnormalities” were present. They claimed to find CCSVI in 100 % of 109 individuals with multiple sclerosis (MS) and in none of 177 healthy controls. Zamboni’s group subsequently reported an uncontrolled treatment trial of cerebral venoplasty, which was termed the “liberation procedure” and claimed that the procedure benefited people with MS. The Zamboni reports were received with considerable skepticism, regarding both their biological plausibility and the claims of 100 % sensitivity, specificity, positive predictive value and negative predictive value. No investigators have subsequently been able to replicate the Zamboni observations. Although some additional reports have indicated finding venous abnormalities in more MS patients than in other groups, most have either found no association of CCSVI with MS, or else have found substantial numbers of controls, either healthy or with other neurological disease, to have the abnormalities. The original Zamboni reports were widely publicised in the mainstream media, especially in Canada and sparked a raging controversy in the social media. Patients clamoured for trials of cerebral venoplasty and others demanded its availability or travelled around the globe to undergo the procedure. The Canadian Institutes of Health Research have now solicited proposals for a Phase I/II clinical trial. At this point, additional scientific studies, including many funded by the National Multiple Sclerosis Society and the Multiple Sclerosis Society of Canada, are moving toward completion and will hopefully allow a proper judgment of the validity of the concept of CCSVI in relation to MS. In the meantime, it is important that physicians remain respectful of patients’ views, but that they are not reticent about expressing their own professional opinions based on available evidence, while emphasising the importance of proper scientific research.

Author:

Aaron Miller

Edition:

European Neurological Review - Volume 7 Issue 1 - Spring 2012

Transthyretin-associated Familial Amyloid Polyneuropathy – Current and Emerging Therapies

c.halagiera — Wed, 02 May 2012 14:08:12 +0000

Amyloidoses encompass a heterogeneous group of disorders characterised by the accumulation and extracellular deposition of insoluble aggregates of misfolded fibrillar proteins termed amyloid, which can lead to tissue damage and organ dysfunction.¹ They can be exceptionally rare or rather frequent, acquired or hereditary, localised or systemic, quite indolent or life-threatening. Amyloidoses are classified based on the main protein forming the deposits and include, as of today, 28 different forms.^2,3

Abstract:

Transthyretin-associated familial amyloid polyneuropathy (TTR-FAP), the most common form of systemic hereditary amyloidosis worldwide, is a late-adult-onset autosomal dominant disease caused by mutations in the TTR gene, with peaks in prevalence in endemic areas. The clinical picture is dominated by a progressive length-dependent polyneuropathy with onset in the feet with loss of temperature and pain sensations, accompanied by life-threatening autonomic dysfunction and infiltrative cardiomyopathy, as well as ocular disturbances. Variable expressivity, in terms of age of onset and involvement of extra-neurological sites, can be due to different mutations, but is also observed among individuals with the same mutation in different countries. Therefore diagnosis of TTR-FAP is often a challenge and must rely on careful clinical assessment combined with a multidisciplinary approach. Elimination of the synthesis of mutated TTR, through liver transplantation, may arrest the progressive neuropathy but not the cardiac and ocular involvement. Novel drugs have recently been developed based on a better understanding of the molecular mechanisms of the disease. Drugs that prevent the misfolding and deposition of mutated TTR have entered clinical trials, and one of these, tafamidis meglumine, has been approved in Europe and is now clinically available. Other medicines are now in the pipeline aimed at suppressing the expression of the mutated TTR gene or at promoting amyloid fibril destructuration, favouring resorption of amyloid deposits. These recent advancements provide grounded hope of an imminent significant improvement in the care of this life-threatening multi-system disease.

Acknowledgements: This work was supported by the Ricerca Finalizzata Malattie Rare, Italian Ministry of Health, Istituto Superiore di Sanità (526D/63), Ministry of Research and University (2007AESFX2-003), and Italian Association for Cancer Research Special Program Molecular Clinical Oncology (grant 9965). Mario Nuvolone is partially supported by an investigator fellowship of Collegio Ghislieri, Pavia. We are indebted to Dr Merrill Benson for generously sharing the table of the transthyretin mutations.

Author:

Mario Nuvolone

Laura Obici

Giampaolo Merlini

Edition:

European Neurological Review - Volume 7 Issue 1 - Spring 2012

Update on Amyloid-associated Intracerebral Haemorrhage

c.halagiera — Wed, 02 May 2012 14:20:18 +0000

Cerebral congophilic or amyloid angiopathy (CAA) is a clinicopathological entity that has been recognised since the early part of the 20th century.¹ It is now considered a common cause of primary non-traumatic brain haemorrhage and traditionally it was described in elderly patients who were thought to be normotensive. Because of its frequent association with Alzheimer’s disease (AD), CAA has become a primary focus of scientific inquiry.

Abstract:

Cerebral congophilic or amyloid angiopathy (CAA) is a clinicopathological entity that is considered a common cause of primary non-traumatic brain haemorrhage in the elderly. CAA is frequently associated with Alzheimer’s disease (AD) and has become a primary focus of scientific inquiry. The spectrum of intracerebral haemorrhage (ICH) that may occur in CAA includes: cerebral lobar haemorrhages, deep haemorrhages, purely subarachnoid and subdural haemorrhages and cerebral microbleeds. CAA is also associated with microinfarcts, leukoencephalopathy and superficial siderosis. This brief article will provide an update on the advances in our understanding of CAA-associated ICH with a focus on the following topics: neuropathology and mechanism of CAA-related haemorrhage; epidemiology, including genetic and other possible risk factors; clinical presentation; diagnosis, including newer imaging modalities; and prospects for prevention and treatment.

Author:

Rebbeca Grysiewicz

Philip B Gorelick

Edition:

European Neurological Review - Volume 7 Issue 1 - Spring 2012

Involvement of Nutrients in the Pathogenesis or Management of Alzheimer’s Disease

c.halagiera — Wed, 02 May 2012 16:46:15 +0000

This article examines the possible involvement of nutrients in the pathogenesis, prevention, or management of Alzheimer’s disease (AD). Nutrients are defined here as food constituents that are essential for preventing or treating the clinical syndromes that develop when they are deficient. In general, they act as substrates or co-factors for enzymes and thereby sustain growth and metabolism.

Abstract:

The number of hippocampal and cortical synapses is diminished in early Alzheimer’s disease (AD) and this loss, which is well correlated with the onset of cognitive deficits, probably reflects both an acceleration in their breakdown and a slowing in their synthesis, perhaps consequent to the concurrent decrease in dendritic spines. No strategies have been identified for increasing the number of synapses. Synaptogenesis requires adequate amounts of highly specialised synaptic membrane and activation of a process for shaping this membrane, initially into dendritic spines and neurites and then into the synapses themselves. Both can be enhanced by providing, concurrently, three circulating compounds present in the diet – uridine (as its monophosphate), docosahexaenoic acid (DHA) and choline – which can be rate-limiting precursors in membrane phosphatide synthesis. The uridine, as uridine triphosphate (UTP), also activates brain P2Y receptors, which facilitate neuronal differentiation and affect the production of synaptic proteins. In two large-scale clinical trials, patients with early AD who received the precursors and cofactors orally for up to 24 weeks exhibited significant improvements in memory indices.

Author:

Richard J Wurtman

Edition:

European Neurological Review - Volume 7 Issue 1 - Spring 2012

Deep Brain Stimulation for Parkinson’s Disease – A Review

c.halagiera — Wed, 02 May 2012 16:50:07 +0000

Any surgical procedure requires two things to be successful: selecting the correct patient and performing the operation correctly.

The various operations of deep brain stimulation (DBS) for Parkinson’s disease (PD) are not particularly difficult. They comprise a series of steps that must be performed in an appropriate sequence and can be learned by most neurosurgeons within a year of fellowship training. The selection of the ideal patient, however, is much more difficult and is as much an art as a science.

Abstract:

The majority of patients with Parkinson’s disease (PD) can be treated with medications. As the disease progresses, however, certain symptoms may evolve that are refractory to medical therapy but ideally suited to surgical intervention. Tremor, dyskinesia and motor fluctuation can be effectively treated with deep brain stimulation (DBS). This article highlights which PD patients can benefit from DBS and summarises how the operations are performed and what are the expected outcomes (and potential complications). The relevant literature is reviewed for experienced clinicians and our personal bias is highlighted for those new to the field (and hoping to avoid our early mistakes).

Acknowledgements: Christopher R Honey would like to acknowledge the patients of British Columbia with Parkinson’s disease, who have entrusted their lives to our team. We are honoured to have cared for them, humbled by their bravery and more knowledgeable for having treated them.

Author:

Christopher R Honey

Manish Ranjan

Edition:

European Neurological Review - Volume 7 Issue 1 - Spring 2012

Non-motor Symptoms in Parkinson’s Disease

c.halagiera — Wed, 02 May 2012 16:57:55 +0000

The degeneration of the dopaminergic nigrostriatal system and parkinsonism (rest tremor, rigidity, bradykinesia and postural instability/gait disorder) represent only one aspect of Parkinson’s disease (PD), a multifaceted and complex disorder.¹ In addition to this typical motor dysfunction, non-motor symptoms (NMS) also significantly reduce of quality of life.^2–4 Several non-motor features are associated with deficits in extranigral dopaminergic pathways (e.g. mesolimbic, mesocortical), while others involve non-dopaminergic systems in the nervous system (e.g.

Abstract:

In addition to typical motor dysfunction (parkinsonism), diverse non-motor symptoms (NMS) are frequently observed in patients with Parkinson’s disease (PD). Some NMS may antedate the diagnosis of PD. Examples of NMS include cognitive impairment, autonomic dysfunction, visual dysfunction, sleep abnormalities and psychiatric disorders. NMS are associated with wide-ranging abnormalities in extranigral dopaminergic systems and non-dopaminergic (e.g. cholinergic, noradrenergic, serotoninergic) systems. The type and severity of NMS vary based on age, disease severity and predominant motor symptoms. NMS can be disabling and reduce quality of life. Treatment of NMS can be challenging. Some NMS are helped by dopaminergic treatment, whereas others can be induced or exacerbated by treatments that help the motor dysfunction. Physicians should probe their PD patients about their NMS and address them for better care. Clinical trials should incorporate NMS as outcomes for more meaningful conclusions on the effect of treatments under investigation.

Author:

Ergun Y Uc

Jon Tippin

Kelvin L Chou

Bradley A Erickson

Kevin C Doerschug

Decontee M Jimmeh Fletcher

Edition:

European Neurological Review - Volume 7 Issue 1 - Spring 2012

Ischaemic Stroke – Stenting versus Surgery for Carotid Disease

c.halagiera — Wed, 02 May 2012 17:11:17 +0000

The purpose of this article is twofold: first, to review the studies comparing carotid endarterectomy (CEA) with medical treatment to help decide who should undergo revascularisation; and secondly, to review studies comparing carotid angioplasty and stenting (CAS) versus CEA to see how they should be revascularised. Extracranial internal carotid artery stenosis is a leading cause of ischaemic strokes and transient ischaemic attacks (TIAs).

Abstract:

Extracranial internal carotid artery stenosis is one of the most common and best studied causes of stroke. Revascularisation with carotid endarterectomy (CEA) has been shown to be beneficial for patients with severe stenosis associated with stroke or transient ischaemic attack (TIA) and for many patients with moderate stenosis associated with stroke or TIA. CEA has also been shown to be beneficial for patients with asymptomatic severe stenosis if they have a reasonable expected lifespan and surgical risk, but the benefit is greater for men compared with women. Carotid angioplasty and stenting (CAS) has become a viable alternative procedure for carotid revascularisation with less risk of major bleeding complications and cranial nerve injury. Randomised studies of CEA versus CAS have found that the endovascular approach is associated with a lower risk of myocardial infarction but a higher risk of peri-procedural stroke which has a greater impact on long-term quality of life. Thus, recommending CEA or CAS must be based upon individual patient characteristics and their preferences, but at this point it appears that most patients should still be receiving CEA if an intervention is required.

Author:

Swaroop Pawar

Steven R Messé

Edition:

European Neurological Review - Volume 7 Issue 1 - Spring 2012

The Evolving Role of the Multiple Sclerosis Nurse – Implications of Future Management Directions

c.halagiera — Wed, 02 May 2012 17:21:11 +0000

Multiple sclerosis (MS) specialist nurses are pivotal members of the multidisciplinary team, all having varying responsibilities such as symptom management, drug initiation and drug monitoring in people with MS. During the past two decades the role of MS nurses has evolved owing to expanding management strategies and new approaches to MS treatment.

Abstract:

The role of the multiple sclerosis (MS) nurse is constantly evolving, owing to the introduction of new MS therapies and new patient treatment and support strategies. The second MS nurse symposium, ‘The Evolving Role of the MS Nurse: Implications of Future Management Directions’ took place in Athens between 22–24 September 2011 and was attended by approximately 300 participants from 30 countries. Presentations at the symposium outlined the mechanisms of action and clinical evidence for novel therapies for MS treatment. The importance of making clinical trial data available and understandable to people with MS was addressed, followed by a summary of the latest data on established MS therapies and an update on autoinjectors and their role in improving adherence. Novel patient support strategies were outlined followed by presentations by MS nurses from different countries who discussed their roles and their opportunities to evolve against a background of very different healthcare systems. Group discussions of typical MS case examples emphasised the need for good communications and relationships between patients and MS nurses. The final session focused on communication skills, highlighting ‘tips’ for engaging with people with MS and examining the challenges that different patient expectations and communication media can bring.

Acknowledgement: Editorial assistance was provided by James Gilbart at Touch Briefings.

Support:

The publication of this article was funded by Novartis. The views and opinions expressed are those of the authors and not necessarily those of Novartis.

Author:

Chrysa Chrysovitsanou

Del Thomas

Martin Duddy

Edition:

European Neurological Review - Volume 7 Issue 1 - Spring 2012

3,4-diaminopyridine Phosphate in the Treatment of Lambert–Eaton Myasthenic Syndrome

c.halagiera — Wed, 02 May 2012 18:13:53 +0000

Lambert–Eaton myasthenic syndrome (LEMS) is a rare neuromuscular disorder affecting around 1/100,000 people in Europe, although because it may go undiagnosed in many patients, its true prevalence may be considerably higher.¹LEMS results from insufficient synaptic release of acetylcholine, which disrupts peripheral cholinergic neurotransmission. This is caused by autoimmune antibodies directed against the P/Q-type voltage-gated calcium channels (VGCCs). The loss of functional VGCCs reduces the calcium-dependent quantal release of the neurotransmitter acetylcholine.

Abstract:

3,4-diaminopyridine (3,4-DAP, amifampridine) is the leading treatment for Lambert–Eaton myasthenic syndrome (LEMS), an autoimmune disorder with impaired neuromuscular transmission, for which few effective medications are currently available. 3,4-DAP has been available as a therapy for LEMS in special treatment programmes for approximately 25 years. As an unlicensed drug, doses for oral administration are required to be compounded by local, hospital or other compounding pharmacies from the base chemical. Administering the correct dose of 3,4-DAP is critical; overdosing can increase the risk of seizures and other adverse events, while underdosing can result in a substantial loss of efficacy or even treatment failure. Two recent studies, have shown a wide variation in the 3,4-DAP content of compounded preparations (22.2–125.2 %, n=9) and (53.5–128.5 %, n=21), thereby reflecting the possibility of patients receiving dosages that might be above safety limits or even markedly below efficacy limits. This inconsistency results from the variable quality and instability of the base chemical and compounding errors. A formulation of 3,4-DAP phosphate salt has now been licensed in Europe and the US with orphan medicinal product status and appears to be as efficacious as the base in relieving the symptoms of LEMS.

Acknowledgements: Editorial assistance was provided by Touch Briefings and funded by BioMarin Europe Limited.

Support:

The publication of this article was funded by BioMarin Europe Limited. The views and opinions expressed are those of the author and not necessarily those of BioMarin Europe Limited.

Author:

Jörn Peter Sieb

Edition:

European Neurological Review - Volume 7 Issue 1 - Spring 2012

Childhood Absence Epilepsy – A Review of Treatment Strategies and Perspectives for the Future

c.halagiera — Wed, 02 May 2012 18:17:59 +0000

Childhood absence epilepsy (CAE) is one of the most common forms of paediatric epilepsy, accounting for between 10 and 17 % of all cases of childhood onset epilepsies.¹ CAE is defined by age-related onset, clinical and electrographical characteristics, and a presumed genetic aetiology.² The syndrome typically begins at between four and eight years of age in an otherwise healthy child.

Abstract:

Childhood absence epilepsy (CAE) is one of the most common forms of paediatric epilepsy. However, there is still a gap between the prevalence of CAE in paediatric epilepsies and the paucity of available data regarding its therapeutic management. Only nine randomised controlled trials have been published in the field over the past four decades, with many suffering from major methodological limitations. A recent large randomised double-blind controlled trial reported that ethosuximide and sodium valproate are the most effective anti-epileptic dugs in CAE and that cognitive performance appears to be better with ethosuximide than with sodium valproate. Although lamotrigine also demonstrated anti-absence properties in the same trial, it proved to be significantly less efficacious than ethosuximide or sodium valproate. Despite these recent advances, several questions, including long-term outcomes, management of refractory CAE and treatment duration, remain unanswered and further studies are required to refine therapeutic decisions.

Author:

Sylvain Rheims

Philippe Ryvlin

Edition:

European Neurological Review - Volume 7 Issue 1 - Spring 2012

Sudden Unexpected Death in Epilepsy – An Overview of Current Understanding and Future Perspectives

c.halagiera — Wed, 02 May 2012 18:23:36 +0000

People with epilepsy have a two- to threefold increased mortality¹ and are 24 times more likely to die of sudden death compared with the general population.² Although injuries associated with seizures, suicides, adverse effects of medications and the underlying aetiology of the epilepsy contribute to this increased mortality, sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy.

Abstract:

Sudden unexpected death in epilepsy (SUDEP) is likely to be the most common cause of disease-related mortality in people with epilepsy. The most commonly encountered scenario is that a previously healthy person is found dead in bed by family. Patients with frequent generalised tonic-clonic seizures are at highest risk but SUDEP can occur in patients who have never had convulsions. The mechanisms of SUDEP are poorly understood but seem to be related to seizure-related cardiac, respiratory or cerebral dysfunction. Seizure control is the only clear strategy to prevent SUDEP but that is not possible in the 30 % of patients with treatment-resistant epilepsy. Understanding the pathophysiology of SUDEP may lead to prevention strategies for patients who continue to have seizures despite maximal therapy.

Author:

Daniel Friedman

Lawrence J Hirsch

Edition:

European Neurological Review - Volume 7 Issue 1 - Spring 2012

Management of Neuropathic Pain – Current Insights and Future Perspectives

c.halagiera — Wed, 02 May 2012 18:29:58 +0000

Neuropathic Pain Definition, Diagnosis and Clinical Presentation

Abstract:

The management of neuropathic pain remains very challenging and very much an art. Despite the publication of multiple consensus guidelines on the management of neuropathic pain, a significant subpopulation of patients with neuropathic pain are not afforded adequate relief, employing various treatment algorithms with conventional pharmacological therapeutic strategies. First-line agents for the treatment of neuropathic pain include: tricyclic antidepressants, selective serotonin/norepinephrine re-uptake inhibitors, calcium channel α2-δ ligands and, in certain cases of focal neuropathic pain, a lidocaine patch. Novel analgesics under development may include: purinergic receptor modulators, cannabinoid receptor modulators, neurokinin-1 (NK-1) receptor modulators, glial modulators, rostral ventral medulla ‘on-cell’ modulators, chemokine receptor modulators, toll-like receptor modulators, modulators of tetrahydrobiopterin synthesis and/or chemically re-engineered conotoxins. It is hoped that future agents and/or combinations of agents may be helpful to this refractory subpopulation.

Author:

Howard S Smith

Sukriye Damla Kara

Charles E Argoff

Edition:

European Neurological Review - Volume 7 Issue 1 - Spring 2012

Transcutaneous Vagus Nerve Stimulation

c.halagiera — Tue, 03 Jan 2012 17:16:32 +0000

Drug-resistant epilepsy accounts for more than 30 % of epileptic patients.¹ Alternative treatment options are resective neurosurgery, deep brain stimulation and invasive vagus nerve stimulation (VNS).² Invasive stimulation of the cervical branch of the vagus nerve has been shown to be highly effective in clinical trials, with a responder rate of approximately 60 %.^3,4 Surgically and technically induced complications include electrode fractures, deep wound infections, transient vocal cord palsy, cardiac arrhythmia under test stimulation, electrode malfunction an

Abstract:

Invasive vagus nerve stimulation (VNS) is an approved treatment for drug-resistant epilepsy. Besides its recognised clinical efficacy, there are major drawbacks, such as invasiveness and a great many side effects. Therefore there is a medical demand for transcutaneous VNS (t-VNS^®), which combines selective, non-invasive access to vagus nerve afferents with a low risk profile. Both treatments excite thick myelinated fibres of vagus nerve branches that project to the nucleus of the solitary tract in the brainstem. Preclinical data emphasise the equivalent anticonvulsive effects of both methods. Based upon the common mode of action and the first clinical data, the t-VNS device received Conformité Européenne (CE) approval. Besides the approved intended use for drug-resistant epilepsy and depression, a future clinical trial will address the efficacy of t-VNS in chronic pain.

Support: The publication of this article was funded by cerbomed GmbH.

Author:

Jens Ellrich

Edition:

European Neurological Review - Volume 6 Issue 4

Advanced Neuroimaging for Modern Epilepsy Surgery

c.halagiera — Tue, 03 Jan 2012 19:56:56 +0000

When neurosurgeons first attempted to treat epilepsy by means of surgery in the late 1800s, they were operating on ‘invisible’ lesions. Without any imaging or electrophysiological technology, MacEwen and Horsley operated under the principles of functional cerebral localisation developed largely by John Hughlings Jackson.¹ Epilepsy surgery has come a long way, as now epileptologists and neurosurgeons are armed with a battery of tools for diagnosis and treatment of epilepsy. These tools have fundamentally changed the way we study and treat this enigmatic disease.

Abstract:

Localising the onset of seizures to guide epilepsy surgery can be notoriously difficult. Modern neuroimaging has revolutionised the field by improving the diagnosis and treatment of epilepsy. In order to ameliorate seizures without causing new neurological morbidity, many imaging tools have been developed to guide safe and effective resective surgery. In this article, we discuss recent advances in structural imaging using ultrahigh-field magnetic resonance imaging, metabolic functional imaging techniques of positron emission tomography and single photon emission computed tomography and electrophysiological imaging using magnetoencephalography. Our goal is to provide an overview of these state-of-the-art imaging modalities, their role in guiding surgery, and how they are incorporated into the pre-surgical evaluation of epilepsy.

Acknowledgements: The authors would like to acknowledge Christopher Hess and Pratik Mukherjee from the Department of Radiology as well as Spencer Behr from the Department of Nuclear Medicine for interpretation of imaging studies. The authors would also like to acknowledge the Journal of Neurosurgery and the American Association of Neurological Surgeons for permission to reproduce printed material for the purpose of this publication.

Author:

Doris D Wang

Carlos Santos-Sanchez

Paul A Garcia

Edward F Chang

Edition:

European Neurological Review - Volume 6 Issue 4

Frovatriptan for the Acute Treatment of Migraine

c.halagiera — Tue, 03 Jan 2012 20:29:35 +0000

Frovatriptan is a 5HT1B/1D receptor agonist¹ and has been developed as a triptan with a long terminal half-life (t_½).² Recurrence, the relapse of migraine headache after an initial successful treatment, is a major problem in migraine treatment.¹ After treatment with other triptans, recurrence occurs in 30–40 % of treated attacks.¹ The triptans, apart from frovatriptan, have a relatively short t_½ of two to five hours.^1,3 Frovatriptan has a t_½ of 26 hours and this may reduce the likelihood of early migraine r

Abstract:

Frovatriptan 2.5 mg has been investigated for the treatment of moderate or severe migraine attacks in six placebo-controlled, randomised controlled trials (RCTs). The mean headache relief (a decrease from moderate or severe to none or mild) was 43 % after frovatriptan and 24 % after placebo. The mean therapeutic gain (active minus placebo) was 19 % (95 % confidence interval 16–22 %). In one large comparative RCT, sumatriptan 100 mg was superior to frovatriptan 2.5 mg for headache relief at two hours (47 versus 37 %). In three cross-over RCTs in which the patients treated migraine attacks as early as possible, frovatriptan 2.5 mg was quite similar to zolmitriptan 2.5 mg, rizatriptan 10 mg and almotriptan 12.5 mg for preference – the primary efficacy measure. It is concluded that frovatriptan is not the triptan of first choice in established moderate to severe migraine attacks (based on systematic reviews and one comparative RCT). However, if the patients can treat their migraine attacks at the start of an attack (and are not triptan-resistant), then frovatriptan is a reasonable treatment choice among the triptans.

Author:

Peer Tfelt-Hansen

Edition:

European Neurological Review - Volume 6 Issue 4

An Overview of the Treatment Options for Acute Migraine

c.halagiera — Tue, 03 Jan 2012 21:03:46 +0000

Migraine is a common disabling headache disorder, affecting about 12 % of the US and other Western populations. The social and economic impact of the disease is considerable. It is more prevalent in women than in men, and in the age range 30–50 years.^1,2

Abstract:

Migraine is a primary headache disorder associated with a high socioeconomic burden. The first step in effective migraine management, following confirmation of the diagnosis, is patient education: the condition is carefully explained, to ensure that it is properly understood, and realistic expectations are set. The choice of acute treatment has changed over time as the available therapeutic options have increased. Abortive migraine therapy can be either specific (ergot derivatives and triptans) or non-specific (analgesics and non-steroidal anti-inflammatory drugs). Even though acute symptomatic therapy can be optimised, migraine remains a chronic and potentially progressive condition.

Author:

Fabio Antonaci

Natascia Ghiotto

Maurizio Evangelista

Edition:

European Neurological Review - Volume 6 Issue 4

Complex Regional Pain Syndrome – Diagnosis, Treatment and Future Perspectives

c.halagiera — Tue, 03 Jan 2012 22:31:29 +0000

Complex regional pain syndrome (CRPS) is a painful disorder of the extremities, characterised by sensory, autonomic, vasomotor, motor and trophic disturbances (see Figures 1 and 2). CRPS mostly occurs after a trauma, such as a fracture or an operation, but can also develop without a preceding event.^1,2 In the Netherlands, approximately 4,300 patients develop CRPS each year, whereby females are affected three times more than males and the highest incidence is found between the age of 61 and 70 years.³

Diagnosing Complex Regional Pain Syndrome

Abstract:

Complex regional pain syndrome (CRPS) is a pain syndrome of the extremities that can result in severe disability. CRPS is diagnosed using diagnostic Budapest criteria based on signs and symptoms, whereby sensory, autonomic, vasomotor, motor and trophic disturbances are assessed. Many pathophysiological mechanisms are proposed in the development and disease course of CRPS, starting with exaggerated inflammation and resulting in vascular deregulation, central sensitisation and cortical reorganisation. Treatment is based primarily on reducing inflammation by using medicinal anti-inflammatory therapy and increasing motor function by physiotherapy. Furthermore, pain reduction, normalisation of vasomotor and motor function, and psychological interventions might be needed. Future research should focus on the efficacy of anti-inflammatory therapy, effective rehabilitation programmes, modulating neuropathic pain and cortical reorganisation.

Author:

Sigrid GL Fischer

Roberto SGM Perez

Edition:

European Neurological Review - Volume 6 Issue 4

Combination Therapy in Moderate to Severe Alzheimer’s Disease – Overview and Discussion Points for the Future

c.halagiera — Tue, 03 Jan 2012 11:57:40 +0000

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder which presents clinically as progressive cognitive impairment, loss of ability to carry out activities of daily living and the development of behavioural problems. Currently, research is focused on new medications to prevent or slow the advancement of the disease, and on techniques for earlier diagnosis. However, to date, medications aimed at disease modification have failed in clinical trials owing to lack of effect, or perhaps because they have not targeted a sufficiently early AD population.

Abstract:

Two effective symptomatic therapies are available for Alzheimer’s disease: the cholinesterase inhibitors (ChEIs) and memantine, an N-methyl-D-aspartate receptor antagonist. Current data demonstrate that combination therapy with memantine and a ChEI produces symptomatic benefits in all domains of AD. The benefits of combination therapy are greater than those of ChEI monotherapy, are sustained long term and appear to increase with time.

Acknowledgement: Editorial support was provided by Cambridge Medical Communication Ltd and was funded by H. Lundbeck A/S.

Author:

José L Molinuevo

Edition:

European Neurological Review - Volume 6 Issue 4

How Reversible are ‘Reversible Dementias’?

c.halagiera — Tue, 03 Jan 2012 12:22:20 +0000

Dementia is a syndrome that can have multiple causes and is characterised by deterioration in different domains of cognition, especially memory, language, praxis, visual perception and executive function.¹ It is estimated that the number of people with dementia will increase dramatically over the next few decades,² presenting a tremendous burden for patients, spouses and other family carers, and society. Consideration of the differential diagnosis of dementia is a complex process, and accurate diagnosis is challenging.

Abstract:

Reversible dementias comprise different groups of disorders of variable aetiologies, such as structural brain lesions or metabolic, infectious, toxic, autoimmune, paraneoplastic and psychiatric disorders. When patients present with cognitive symptoms, especially in the younger age groups, the first thought of the attending neurologist should be to try to identify an underlying treatable cause. The incidence of degenerative dementia rises with older age and its symptoms progressively become more evident and typical; in such cases, a differential diagnosis is limited and the chance of uncovering a treatable disorder is minimal. However, although uncommon, treatable dementias or dementia-like symptoms do exist. Future studies with better design and methodology, as well as longer observation periods and larger patient populations, are needed to clarify the controversial issues concerning the epidemiology and accurate diagnosis of, and treatment possibilities for, reversible dementias.

Author:

Panagiotis Ioannidis

Dimitris Karacostas

Edition:

European Neurological Review - Volume 6 Issue 4

New Diagnostic Criteria for the Behavioural Variant of Frontotemporal Dementia

c.halagiera — Tue, 03 Jan 2012 13:09:22 +0000

Frontotemporal dementia (FTD) is a neurodegenerative disorder mainly affecting the frontal and/or temporal lobes, leading to dementia with prominent behavioural and/or language disturbances. Symptom onset is most often between 45 and 65 years. Arnold Pick described the disease with remarkably focal lobar atrophy in 1892 and it was later termed Pick’s disease by Alois Alzheimer.^1,2 At present, it is known that frontotemporal lobar degeneration (FTLD) with Pick bodies consisting of tau-positive intraneuronal inclusions is not the only pathological correlate of FTD.

Abstract:

In September 2011, the International Behavioural Variant Frontotemporal Dementia Criteria Consortium established a new set of clinical diagnostic criteria for the behavioural variant of frontotemporal dementia (bvFTD). Following the 1998 criteria by Neary et al., where five core items had to be present to make a diagnosis of bvFTD, the new criteria incorporate six clinical hallmarks and demand that at least three of these are present. Moreover, a degree of probability and a role for neuroimaging findings are introduced within the criteria. The new diagnostic criteria have a sensitivity of 76 % for probable bvFTD and a sensitivity of 86 % for possible bvFTD. They provide a good starting point for a more accurate diagnosis of bvFTD.

Author:

Yolande AL Pijnenburg

Edition:

European Neurological Review - Volume 6 Issue 4

Rapidly Progressive Dementia – Clinical Aspects and Management

c.halagiera — Tue, 03 Jan 2012 13:41:34 +0000

The term rapidly progressive dementia (RPD) is used to describe cases with a progression course which usually ranges between weeks and months.^1–4 The subacute nature of RPD excludes other conditions with fulminant progression such as infectious or metabolic acute encephalopathies, which progress within hours or days and typically commence as an acute confusional state.

Abstract:

Although no precise definition for rapidly progressive dementia (RPD) exists, this term is generally used to refer to cases with significant and progressive cognitive impairment that occurs over weeks or months. RPD represents an unusual but severe condition that causes distress not only for patients and their relatives but also for the clinicians involved, as multiple investigations and decisions about management must be made urgently to avoid misdiagnosing a treatable condition and to preserve as much of the neural tissue as possible from definite damage. While Creutzfeldt-Jacob disease (CJD) has for a long period of time been regarded as the prototype of RPD, this infrequent but severe condition can be produced by an extensive variety of causes such as various endocrine, metabolic or toxic disorders, central nervous system (CNS) infections, primary or secondary CNS neoplasms, various CNS vasculitides and various autoimmune conditions in which autoantibodies against neural tissue are produced, whether in the presence of a neoplasm or not. However, even in the more common and usually slowly progressive dementias such as Alzheimer’s disease, frontotemporal lobar degeneration, dementia with Lewy bodies and other degenerative dementias, as well as vascular dementia, establishment and progression of the disease is occasionally surprisingly accelerated, leading to a clinical presentation of RPD. The few published case series of RPD have shown that the relative frequency of underlying diseases depends mainly on the clinical setting. Thus, CJD has been found to be the most prevalent cause in referral centres for spongiform encephalopathies, while secondary causes are more prevalent in general referral centres for dementia diagnosis. In clinical practice, for the cases presenting with RPD, the diagnostic procedure must be exhaustive, starting with a detailed clinical evaluation and proceeding to a complete laboratory work-up and sophisticated neuroimaging studies. There has been recent enormous progress in imaging, with sensitive new sequences of magnetic resonance imaging and immunology; as a result, a plethora of antibodies against the CNS can now be detected in cases of autoimmune dementias, which has dramatically changed the diagnostic approach and early management of cases of RPD. The same favourable effect in clinical practice comes from the accumulated knowledge of the complex clinical picture of various causes of RPD, associated specific neurological features (pyramidal signs, ataxia, myoclonus) and systematic features (weight loss, hyponatraemia, hepatic disorders) and their mode of progression.

Author:

Sokratis G Papageorgiou

Christos Koros

Edition:

European Neurological Review - Volume 6 Issue 4

Neurogenesis in Stroke Treatment

c.halagiera — Tue, 03 Jan 2012 15:22:54 +0000

In the adult rodent brain, neurogenesis occurs primarily in the subventricular zone (SVZ) of the lateral ventricle and in the subgranular zone (SGZ) of the dentate gyrus, and neurogenesis persists for the lifetime of the animal.^1–9 In the adult human brain, neurogenesis occurs in the hippocampus and SVZ.¹⁰ Studies in experimental stroke demonstrate that focal cerebral ischaemia increases neurogenesis in the SVZ and induces SVZ neuroblast migration towards the ischaemic boundary.^11–25 Stroke-induced neurogenesis is present in the adult human brain, even in advan

Abstract:

Findings of stroke-induced neurogenesis in the adult brain have raised hopes that amplification of endogenous neurogenesis contributes to improvement of neurological outcomes. This article briefly reviews stroke-induced neurogenesis and emerging potential therapies aimed at amplification of endogenous neurogenesis during stroke recovery.

Support: The publication of this article was funded by EVER Neuro Pharma GmbH. The views and opinions expressed are those of the authors and not necessarily those of EVER Neuro Pharma GmbH.

Author:

Rui Lan Zhang

Michael Chopp

Edition:

European Neurological Review - Volume 6 Issue 4

The Role of Fluoxetine and Selective Serotonin Re-uptake Inhibitors in Motor Recovery Following Acute Ischaemic Stroke

c.halagiera — Tue, 03 Jan 2012 16:31:43 +0000

Recovery of neurological functions after a stroke has long been a puzzling question for clinicians and scientists. On the one hand, clinicians knew from their own practice that partial recovery was very often observed after a stroke and on the other hand, it was well known that neurons, when destroyed after ischaemia, were not restored despite some very localised neurogenesis.

Abstract:

Until now, recombinant tissue plasminogen activator thrombolysis within the first hours after a stroke has been recognised as the only validated treatment able to improve the spontaneous – and most of the time incomplete – recovery of neurological functions after stroke. However, we have learnt from research over the last decade, in part based on the considerable improvement in neuroimaging techniques, that spontaneous recovery of neurological functions was associated with a large intracerebral re-organisation of the damaged human brain. The question of whether lesioned-brain plasticity can be modulated by external factors such as pharmacological agents is now addressed, with the aim of improving recovery and reducing the final disability of patients. We review the preclinical and clinical arguments for a direct action of selective serotonin re-uptake inhibitors in promoting recovery after stroke in humans.

Author:

François Chollet

Jean Tardy

Jérémie Pariente

Isabelle Loubinoux

Jean-François Albucher

Edition:

European Neurological Review - Volume 6 Issue 4

Autoimmune Comorbid Conditions in Multiple Sclerosis

lata.ravichander — Wed, 14 Mar 2012 19:20:41 +0000

Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system (CNS). Although it is generally considered to be an autoimmune disease, MS may be a heterogeneous condition incorporating different pathologies. The incidence of autoimmune comorbidities in MS patients may help us elucidate the autoimmune aspects of the disease. Furthermore, the presence of autoimmune comorbidities may help us discover new biomarkers with potential predictive value regarding response to treatment, and understand common factors in pathogenesis.

Abstract:

Autoimmune comorbidities occur frequently in multiple sclerosis (MS). They may arise as a consequence of a genetic susceptibility to autoimmunity. Certain pathological mechanisms are common to several autoimmune conditions. In the presence of comorbid autoimmune conditions, certain MS therapeutics may be preferable to others. Autoimmune comorbidity associated with MS could be a factor in predicting response to specific MS therapeutics. Treatment with interferon beta has been reported to precipitate immune-mediated abnormalities or to exacerbate existing autoimmune diseases. In comparison, there are fewer reported cases of treatment-associated comorbidities linked with autoimmune disease in patients taking glatiramer acetate. Knowledge of the factors influencing autoimmune comorbidities may provide insights into the complex pathogenesis of MS and help inform treatment choices.

Author:

Regina Berkovich

Dawood Subhani

Lawrence Steinman

Edition:

US Neurology - Volume 7 Issue 2

Peripheral Nerve Stimulation for Neuropathic Pain

lata.ravichander — Wed, 14 Mar 2012 19:31:14 +0000

Abstract:

Over the last two decades, electrical neuromodulation has become a dominant approach in surgical treatment of medically refractory neuropathic pain, essentially eclipsing multiple available neuroablative procedures. Among different types of neuromodulation, peripheral nerve stimulation (PNS) holds the unique position of being the least invasive—and at the same time the least established in terms of scientific evidence and regulatory approvals. However, it is now gaining tremendous momentum in terms of accumulation of clinical experience and development of new indications. As a matter of fact, recent European approval of PNS for treatment of chronic low back pain and intractable migraine headaches is expected to add legitimacy and marketing support to the entire field of PNS. This article provides an overview of PNS history, reviews current thoughts regarding its mechanism of action, summarizes common indications, clinical outcomes, technical procedural details, and complications, and suggests future directions for PNS development. It appears that PNS today is the most rapidly growing field of neuromodulation—and that does not come as a surprise, considering its potential for treatment of very prevalent and hard-to-treat conditions, such as back pain and headaches. From the point of view of a practicing neurologist, PNS presents an attractive pain management option that combines a high level of efficacy and reproducibility of results with low invasiveness and minimal morbidity. As the worldwide experience with PNS continues to grow, one may expect to see it becoming a widely accepted treatment approach in a variety of clinical conditions.

Author:

Konstantin V Slavin

Edition:

US Neurology - Volume 7 Issue 2

Gamma Knife Radiosurgery for Trigeminal Neuralgia—A Review

lata.ravichander — Wed, 14 Mar 2012 19:40:46 +0000

What is Trigeminal Neuralgia?

Abstract:

Gamma knife radiosurgery (GKRS) evolved from the vision of Lars Leksell as a method of bloodless surgery for treating a wide variety of intracranial pathologies. Since the first GKRS procedure for trigeminal neuralgia (TN) in the early 1970s, thousands of medically refractory patients have been treated, with good results. GKRS has become a first-line treatment for medically refractory TN along with microvascular decompression and percutaneous rhizotomy. GKRS offers the advantages of minimal invasiveness and extremely low risk. When recommending a surgical treatment modality for medically refractory TN, one must consider patient preferences, procedural risks, medical comorbidities, and the success rates of the various approaches. In this context, we review the role of GKRS in the treatment of medically refractory TN.

Author:

Edward A Monaco III

Hideyuki Kano

Ali Kooshkabadi

L Dade Lunsford

Edition:

US Neurology - Volume 7 Issue 2

Intrathecal Drug Delivery for Neuropathic Pain

lata.ravichander — Wed, 14 Mar 2012 19:47:16 +0000

Neuropathic pain may arise from a variety of causes involving either the central or peripheral nervous system, and is typically challenging to treat. The annual incidence of neuropathic pain is estimated to be 1 %, with the burden likely to increase as the population ages.¹ When traditional mainstays of treatment fail to provide relief, more advanced interventions such as neuromodulation and intrathecal therapy may result in symptom palliation.

Abstract:

Neuropathic pain represents a substantial burden on society. The treatment of neuropathic pain is challenging and typically involves multiple medication classes such as anticonvulsants, antidepressants, and opioids. The advent of intrathecal medication delivery in the late 1970s provided an additional option for the treatment of refractory neuropathic pain. This article presents a review of the evidence regarding intrathecal medications for neuropathic pain. There is strong evidence to support the use of intrathecal opioids in malignant pain of mixed characteristics, and moderate evidence for their use in non-malignant, neuropathic pain. The use of baclofen is strongly supported for spasticity, but there is only intermediate-level evidence for its use in neuropathic pain. With respect to clonidine and ziconotide, there is moderate evidence to support their use for neuropathic pain, although the effectiveness of the latter agent is limited by the high incidence of adverse effects. For steroids, there is weak evidence in favor of its use in neuropathic pain, predominantly in combination with opioids. The evidence is moderate to strong for the use of steroids in post-herpetic neuralgia, which must be weighed against the possibility of neurotoxicity if depot steroids are injected.

Author:

David E Jamison

Indy M Wilkinson

Steven P Cohen

Edition:

US Neurology - Volume 7 Issue 2

Cambia® (Diclofenac Potassium for Oral Solution) in the Management of Acute Migraine

lata.ravichander — Wed, 29 Feb 2012 19:18:02 +0000

Migraine is one of the most prevalent neurological illnesses occurring in approximately 10 % of the US population, with a total prevalence of up to 29.6 % if probable migraine is also considered.^1,2 The disorder manifests as episodic pain that is disabling in 50–75 % of patients with migraine.² With nearly one in four households affected by migraine,² the disease results in direct and indirect costs of about $23 billion per year.^3,4 Despite the disabling nature of migraine, 50 % of patients with migraine go undiagnosed.⁵ The diagnosis of m

Abstract:

Migraine is a prevalent and disabling disorder involving central and peripheral neurologic processes that generate inflammatory mediated pain. Cambia® (diclofenac potassium for oral solution), a novel patented form of the anti-inflammatory medication diclofenac potassium, has been approved by the US Food and Drug Administration for the acute treatment of migraine. Clinical trial data have demonstrated that this formulation offers a four-fold decrease in time of onset of relief compared with conventional diclofenac, which has comparable efficacy to triptan medication. It has also proven effective in a real-world setting. Over the past few years, it has been established that migraine treatment that is administered early may prevent central sensitization and improve treatment outcomes. Given the importance of early intervention in migraine treatment, this medication offers rapid, convenient, and effective relief with a favorable side-effect profile. This review describes migraine pathophysiology, treatment rationale, clinical trial results, and real-world experience with the use of this new medication.

Author:

Kevin Kahn

Edition:

US Neurology - Volume 7 Issue 2

Use of the Unified Parkinson’s Disease Rating Scale Activities of Daily Living Subscale to Assess Response to Rasagiline in Early Parkinson’s Disease

lata.ravichander — Wed, 29 Feb 2012 19:25:10 +0000

Abstract:

Various assessment scales are used to measure the severity and rate of progression of Parkinson’s disease (PD)—for example, the Unified Parkinson's Disease Rating Scale (UPDRS) and its Activities of Daily Living (ADL) subscale. The relative merits of these scales for accurately determining the degree of disease progression have recently come under scrutiny. Analyses of data from the recent Attenuation of disease progression with Azilect given once daily (ADAGIO) trial demonstrated that patients receiving early-start rasagiline (Azilect®, Teva Neuroscience, North Wales, PA) 1 mg/day experienced slower disease progression, as assessed by their mean total UPDRS score, than patients receiving placebo followed by delayed-start rasagiline treatment. Subsequent secondary analyses showed that 1 and 2 mg/day doses of early-start rasagiline delayed the need for antiparkinsonian drugs and improved other parameters, including ADL scores and fatigue, when compared with placebo followed by delayed-start rasagiline. Furthermore, the analyses highlighted that, over time, the motor and mentation sections of the UPDRS-ADL subscale increasingly reflect the response to treatment of the early- and delayed-start rasagiline 1 mg/day patient groups. The results from the ADAGIO trial suggest that rasagiline has potential disease-modifying effects, but more clinical data are required to confirm their effect on PD progression.

Author:

Daniel E Kremens

James Gilbart

Edition:

US Neurology - Volume 7 Issue 2