Showing papers in "Expert Review of Neurotherapeutics in 2013"

Sacroiliac joint pain: a comprehensive review of epidemiology, diagnosis and treatment

Abstract: Sacroiliac joint (SIJ) pain is an underappreciated source of mechanical low back pain, affecting between 15 and 30% of individuals with chronic, nonradicular pain. Predisposing factors for SIJ pain include true and apparent leg length discrepancy, older age, inflammatory arthritis, previous spine surgery, pregnancy and trauma. Compared with facet-mediated and discogenic low back pain, individuals with SIJ pain are more likely to report a specific inciting event, and experience unilateral pain below L5. Owing in part to its size and heterogeneity, the pain referral patterns of the SIJ are extremely variable. Although no single physical examination or historical feature can reliably identify a painful SIJ, studies suggest that a battery of three or more provocation tests can predict response to diagnostic blocks. Evidence supports both intra- and extra-articular causes for SIJ pain, with clinical studies demonstrating intermediate-term benefit for both intra- and extra-articular steroid injections. In those who fail to experience sustained relief from SIJ injections, radiofrequency denervation may provide significant relief lasting up to 1 year. This review covers all aspects of SIJ pain, with the treatment section being primarily focused on procedural interventions.

Cyberchondria: towards a better understanding of excessive health-related Internet use

Abstract: Looking for information about symptoms and illnesses on the Internet is common and often serves useful purposes. However, a number of people who are overly distressed or anxious about their health perform excessive or repeated health-related searches on the Internet, only to become more distressed or frightened - a pattern defined here as cyberchondria. This behavior, which can also be construed as a form of reassurance seeking and occurs as a manifestation of health anxiety and hypochondriasis, is the focus of this article. The antecedents of cyberchondria, factors that maintain it and its consequences are examined conceptually and in light of the relatively little research that has been performed so far. Managing cyberchondria poses a challenge, and several approaches as part of the treatment of health anxiety and hypochondriasis are described. The article makes suggestions for further research on cyberchondria.

Environmental factors in multiple sclerosis.

Abstract: Although genetic susceptibility explains the clustering of multiple sclerosis (MS) cases within families, the changes in MS risk that occur with migration can be explained only by changes in the environment. The strongest known risk factor for MS is infection with Epstein-Barr virus (EBV). Compared with uninfected individuals, the hazard of developing MS is approximately 15-fold higher among individuals infected with EBV in childhood and about 30-fold higher among those infected with EBV in adolescence or later in life. Although the mechanisms underlying this association remain unclear, the data provide strong evidence of a causal relation between EBV infection and MS risk. Relevant aspects of MS epidemiology beyond genetics are not explained by EBV involvement, however, implying the involvement of other factors. Modifiable factors for MS risk include smoking and childhood obesity. Increased risk of MS in individuals with vitamin D insufficiency has been proposed to explain the strong latitude gradient in MS prevalence. Results of case-control studies that relied on prevalent MS cases have been mixed, however, and potentially influenced by selection and recall biases. In a recent case-control study of individuals presenting with a first demyelinating episode, higher levels of vitamin D, sun exposure or actinic damage were found to be associated with reduced MS risk. Two longitudinal studies have thus far been completed. In the first, based on assessment of vitamin D intake from diet and supplements, the risk of MS was found to be 30% lower among women in the highest quintile compared with those in the lowest quintile. In the second study, conducted among young adults in the US military, vitamin D status was assessed by averaging multiple season-adjusted measures of 25-hydroxyvitamin D (25[OH]D). During an average of 5 years' follow-up, MS risk among healthy young adults with serum levels of 25(OH) vitamin D >100 nmol/l was about 60% lower than in individuals of the same age and sex with serum 25(OH) vitamin D levels <100 nmol/l. If confirmed, these findings suggest that a high proportion of MS cases could be effectively prevented by vitamin D supplementation. Furthermore, there is growing evidence that vitamin D insufficiency is a risk factor for conversion from clinically isolated syndrome to MS and for MS progression. Both prevention and treatment trials with vitamin D are needed to confirm these findings and to determine optimal levels of vitamin D.

The comorbidity of ADHD and autism spectrum disorder.

Abstract: ADHD and autism spectrum disorder are common psychiatric comorbidities to each another. In addition, there is behavioral, biological and neuropsychological overlap between the two disorders. There are also several important differences between autism spectrum disorder and ADHD. Treatment strategies for the comorbid condition will also be reviewed. Future areas of research and clinical need will be discussed.

Poor insight into schizophrenia: contributing factors, consequences and emerging treatment approaches

Abstract: Poor insight or unawareness of illness has been commonly observed in schizophrenia and has been long recognized as a potent barrier to treatment adherence and a risk factor for a range of poorer outcomes. Paradoxically, the achievement of insight often poses a different set of problems including depression and low self-esteem. One barrier to the treatment of poor insight has been a lack of understanding of the phenomenon, which causes poor insight to develop and persist over time. Without knowing what promotes poor insight, treatment to date has had little to offer beyond the supportive provision of information. To explore these issues, this article reviews emerging literature on the correlates of poor insight in schizophrenia, and newly developing ways of conceptualizing insight. It then details a number of innovative integrative group and individual treatment approaches in the early stages of development, which take into account some of the potential causal forces behind poor insight, including deficits in neurocognition, social cognition, metacognition and heightened self-stigma. A plan for further research is presented to develop a model of the factors whose interaction influences insight, and to refine and test integrative treatments.

Broad-spectrum micronutrient formulas for the treatment of psychiatric symptoms: a systematic review

Abstract: Ingesting minerals and vitamins in combination makes physiological sense, and research on the use of broad-spectrum formulations for psychiatric symptoms is increasing rapidly. This review covers formulas consisting of at least four vitamins and/or minerals and includes four experimental designs: randomized controlled trials, open-label trials, case–control studies and case studies with within-subject crossovers. Nevertheless, there is evidence for the efficacy of micronutrients in the treatment of stress and antisocial behaviors as well as depressed mood in nonclinical and elderly populations. Many reports studied mood changes in healthy populations, making it difficult to generalize to clinical samples. There is also preliminary support for the treatment of autism with micronutrients. However, despite positive preliminary findings, there are less data available to support efficacy of micronutrient formulas in treating bipolar disorder, attention deficit-hyperactivity disorder and substance abuse/depende...

A critical review of mTOR inhibitors and epilepsy: from basic science to clinical trials.

Abstract: Present medications for epilepsy have substantial limitations, such as medical intractability in many patients and lack of antiepileptogenic properties to prevent epilepsy. Drugs with novel mechanisms of action are needed to overcome these limitations. The mTOR signaling pathway has emerged as a possible therapeutic target for epilepsy. Preliminary clinical trials suggest that mTOR inhibitors reduce seizures in tuberous sclerosis complex (TSC) patients with intractable epilepsy. Furthermore, mTOR inhibitors have antiepileptogenic properties in preventing epilepsy in animal models of TSC. Besides TSC, accumulating preclinical data suggest that mTOR inhibitors may have antiseizure or antiepileptogenic actions in other types of epilepsy, including infantile spasms, neonatal hypoxic seizures, absence epilepsy and acquired temporal lobe epilepsy following brain injury, but these effects depend on a number of conditions. Future clinical and basic research is needed to establish whether mTOR inhibitors are an ef...

Pseudoprogression after glioma therapy: a comprehensive review

Abstract: Over the last decade, pseudoprogression as a clinically significant entity affecting both glioma patient management and the conduct of clinical trials has been recognized as a significant issue. The authors have summarized the literature relative to the incidence, chronological sequence, therapy-relatedness, impact of O-6-methylguanine-DNA methyltransferase methylation status and clinical features of pseudoprogression. Evidence regarding numerous neuroradiologic techniques to differentiate pseudoprogression from tumor recurrence is summarized. The implications of pseudoprogression on prognosis and clinical trial design are substantial, and are reviewed. Relative to this, the overlapping terms pseudoprogression and radiation necrosis are clarified to produce an appropriate basis for future consideration and research regarding this important biological phenomenon.

Meta-analysis: pharmacological treatment of pathological gambling.

Abstract: Background: This meta-analysis investigates the efficacy of pharmacological treatments for pathological gambling (PG). Methods: We searched for randomized, placebo-controlled trials examining pharmacotherapy of pathological gamblers. A fixed-effects model was used to calculate the standardized mean difference (SMD) of the benefit of medication (stratified by class) compared to placebo. Secondary analyses examined the effects of publication bias, year of publication and adherence to intention-to-treat (ITT) principles on reported efficacy of interventions. Results: Meta-analysis included 14 trials involving 1024 participants. Opiate antagonists demonstrated a small but significant benefit compared to placebo (SMD = 0.22 ± 0.10 (95% CI: 0.03–0.41), z = 2.3, p = 0.02). The reported efficacy of opiate antagonists was significantly associated with non-adherence to ITT principles in trials and earlier year of publication. Other medications had non-significant effect sizes compared to placebo but similar in magn...

Mood disorders medications: predictors of nonadherence - review of the current literature.

Abstract: Studies have shown that there are several factors that predict nonadherence among patients with mood disorders. The aim of the present review is to identify the predictors of nonadherence among these patients. A careful review of the literature was conducted investigating several potential predictors of nonadherence among patients with mood disorders. A total of 217 relevant articles from peer-reviewed journals were considered, and articles that met our inclusion criteria (n = 54) were selected for this review. The authors identified several predictors of nonadherence among patients with mood disorders including younger age (below 40 years old), comorbidity with substance use and personality disorders, patients' beliefs, poor insight, illness severity, treatment-related side effects, specific features of the disease and a poor therapeutic alliance. Substance use disorder and illness severity are significant predictors of nonadherence especially in patients with bipolar disorder; whereas, treatment side effects are of primary importance for depressive disorder. The authors could not carry out a meta-analysis given that the studies considered in this review assessed patients at different time points and included different measurements of nonadherence. Moreover, articles cited in this review may reflect the authors' choice, and the authors did not investigate the adherence to a specific class of drugs commonly used in the management of mood disorders. Given the high social, clinical and economic impact of nonadherence among patients who are affected by mood disorders, it is critical to recognize patients at high risk of nonadherence in order to inform future strategies to examine and improve adherence to treatment. Further research is needed to clarify this issue.

Second-generation antipsychotics in the treatment of major depressive disorder: current evidence

Abstract: Major depressive disorder (MDD) is a chronic and recurrent mental condition leading to huge impacts on direct and indirect personal and public medical costs. To overcome such a serious mental disorder, we currently have a number of different classes of antidepressants, such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, noradrenergic and specific serotonin receptor antagonists, dopamine and norepinephrine reuptake inhibitors, along with newly introduced antidepressants (e.g., vilazodone and agomelatine). However, a number of well-controlled clinical trials, meta-analyses and practical clinical studies have found that only a third of such MDD patients remit following adequate antidepressant treatment, while most MDD patients suffer from significant core depressive or residual symptoms during their clinical course. There have been some treatment approaches to overcome such a shortage of antidepressant efficacy, such as augmentation of psychotropics other than antidepressants, switching to a different antidepressant and combinations of different antidepressants. Among these different second treatment options, augmentation treatment has some favorable points compared with the combination and switching option (e.g., maintaining previous antidepressant partial response, synergistic effect between different pharmacological profile and no need to wash out previous antidepressants). Recently, second-generation antipsychotics (SGAs), olanzapine plus fluoxetine, quetiapine extended release and aripiprazole have clearly demonstrated efficacy in the treatment of MDD patients through a number of small-scale, open-label studies or randomized, placebo-controlled clinical trials. Eventually, in November 2007, aripiprazole was the first approved by the US FDA as an adjunctive treatment to antidepressants for treating MDD, followed by the approval of quetiapine and olanzapine plus fluoxetine at 2009. This comprehensive review provides an overview of the clinical trial data of SGAs for treating MDD and clinical issues raised in the use of SGA therapy in patients with MDD in clinical practice.

White matter abnormalities associated with Alzheimer’s disease and mild cognitive impairment: a critical review of MRI studies

Abstract: In this article, the authors aim to present a critical review of recent MRI studies addressing white matter (WM) abnormalities in Alzheimer's disease (AD) and mild cognitive impairment (MCI), by searching PubMed and reviewing MRI studies evaluating subjects with AD or MCI using WM volumetric methods, diffusion tensor imaging and assessment of WM hyperintensities. Studies have found that, compared with healthy controls, AD and MCI samples display WM volumetric reductions and diffusion tensor imaging findings suggestive of reduced WM integrity. These changes affect complex networks relevant to episodic memory and other cognitive processes, including fiber connections that directly link medial temporal structures and the corpus callosum. Abnormalities in cortico-cortical and cortico-subcortical WM interconnections are associated with an increased risk of progression from MCI to dementia. It can be concluded that WM abnormalities are detectable in early stages of AD and MCI. Degeneration of WM networks causes disconnection among neural cells and the degree of such changes is related to cognitive decline.

New second-generation long-acting injectable antipsychotics for the treatment of schizophrenia

Abstract: Long-acting injectable (depot) antipsychotics are one approach in the management of individuals with schizophrenia. Since the introduction of risperidone long-acting injection in 2003, three additional second-generation antipsychotics have become available in a long-acting injectable formulation: paliperidone, olanzapine and aripiprazole. Although these different depot options can help with adherence and thus encourage better treatment outcomes, they differ in terms of specific indications, approved injection sites, needle gauge, injection volume, injection interval, requirements for oral supplementation, availability of prefilled syringes, storage needs and postinjection observation period, as well as potential drug–drug interactions and commonly encountered adverse reactions. After a review of the evidence base, guidance is offered on the appropriate selection among the long-acting injectable formulations of both first and second-generation antipsychotics.

Understanding glioma stem cells: rationale, clinical relevance and therapeutic strategies.

Abstract: Glioblastoma multiforme is one of the most aggressive brain tumors in adults. Despite the use of the best available multimodal therapeutic approaches, the prognosis remains dismal. The identification of glioma stem cells (GSCs) has offered new hope to affected patients, since it could explain, in part, the highly heterogeneous nature of this tumor and its chemo- and radio-resistance. Although still in its infancy, GSC research has unveiled many of its complexities and the theory itself remains controversial. GSC phenotype can significantly vary between patients and a single tumor may present several distinct GSCs. New therapeutic solutions that effectively target this population are of utmost importance, since they may be able to decrease neoplastic recurrence and improve patient survival. Here, we discuss the mechanisms by which GSCs lead to glioma relapse, the main controversies in this field and the most recent treatments that could successfully target this population.

The circadian rhythm in adult attention-deficit/hyperactivity disorder: current state of affairs

Abstract: Adults with ADHD often have sleep problems that are caused by a delay of their internal circadian rhythm system. Such individuals are often typified as 'evening' or 'night' persons. This review focuses on the link between ADHD symptoms and the evening typology through multiple pathways. Etiology of the internal circadian rhythm system, the genetic basis for evening typology, overlap between ADHD symptoms and evening preference and risk factors for various chronic health conditions, including metabolic syndrome and cancer, are discussed. The treatment perspectives to reset the delayed rhythm in adults with ADHD involve psychoeducation on sleep hygiene, melatonin in the afternoon or evening and bright light therapy in the morning.

Chronic pain treatment with opioid analgesics: benefits versus harms of long-term therapy

Abstract: Chronic non-cancer pain (CNCP) is a disabling chronic condition with a high prevalence rate around the world. Opioids are routinely prescribed for treatment of chronic pain (CP). In the past two decades there has been a massive increase in the number of opioid prescriptions, prescribed daily opioid doses and overall opioid availability. Many more patients with CNCP receive high doses of long-acting opioids on a long-term basis. Yet CP and related disability rates remain high, and majority of the patients with CNCP are dissatisfied with their treatments. Intersecting with the upward trajectory in opioid use are the increasing trends in opioid related adverse effects, especially prescription drug abuse, addiction and overdose deaths. This complex situation raises questions on the relevance of opioid therapy in the treatment of CNCP. This article reviews current evidence on opioid effectiveness, the benefits and harms of long-term therapy in CNCP.

Neurotrophins, inflammation and oxidative stress as illness activity biomarkers in bipolar disorder

Abstract: Recent studies highlight the presence of systemic toxicity as an integral dimension of bipolar disorder pathophysiology, possibly linking this mood disorder with other medical conditions and comorbidities. This review summarizes recent findings on possible peripheral biomarkers of illness activity, with a focus on neurotrophins, inflammation and oxidative stress. The possible mechanisms underlying the systemic toxicity associated with acute episodes in bipolar disorder are also discussed. Finally, the authors outline novel therapies that emerge from this new research and the assessment of multiple biomarkers as a potential approach to improving management strategies in bipolar disorder.

Cariprazine, a new, orally active dopamine D2/3 receptor partial agonist for the treatment of schizophrenia, bipolar mania and depression.

Abstract: Cariprazine is a novel drug with partial agonist activity at dopamine D2/3 receptors and six- to eightfold higher affinity for human dopamine D3 over D2 receptors. Results from several placebo-controlled Phase II/III trials in patients with a The Diagnostic and Statistical Manual of Mental Disorders IV diagnosis of schizophrenia or bipolar I disorder suggest that cariprazine is superior to placebo with respect to antipsychotic and antimanic activity. Reports concerning safety and tolerability of cariprazine are mainly favorable, although the rates of treatment-associated adverse events, which most commonly included akathisia and extrapyramidal symptom, are rather high. However, only minor alterations of clinical laboratory values, prolactin concentrations and ECG parameters are reported in cariprazine-treated patients. A new drug application to the U.S. F DA for cariprazine for the treatment of both schizophrenia and manic or mixed episodes associated with bipolar I disorder was submitted in November 2012. A more precise assessment of the clinical properties of this new drug will require additional studies, aimed to compare and contrast cariprazine with other antipsychotic agents.

Non-pharmacological interventions and neuroplasticity in early stage Alzheimer's disease.

Abstract: Non-pharmacological interventions have the potential to reduce cognitive decline and to improve psychosocial aspects in mild cognitive impairment and Alzheimer's dementia, and the absence of side effects makes them a favorable option also for preventive strategies. We provide an overview on recent studies involving cognitive training and reminiscence, stimulating and challenging experiences such as visual art and music, physical activities, and electromagnetic stimulation. We review findings on neuroplasticity in the aging brain and their relevance for cognitive improvement in patients with neurodegenerative diseases. We discuss cognitive reserve and possible mechanisms that drive neuroplasticity and new learning. Finally, we identify promising avenues for future intervention strategies and research, such as combinations of cognitive and pharmaceutical interventions, and individual strategies adapted to the disease stage and tailored to the needs, predispositions and preferences of patients.

Augmentation strategies in obsessive–compulsive disorder

Abstract: Around 40-60% of patients with obsessive-compulsive disorder do not show adequate response to selective serotonin reuptake inhibitors (SSRIs). Augmentation strategies are recommended in people who show partial response to SSRI treatment or poor response to multiple SSRIs. In this article, the authors review the evidence for augmentation strategies. The available evidence is predominantly based on small-scale, randomized controlled trials, open-label trials and case series. Antipsychotic augmentation, especially risperidone, haloperidol, aripiprazole and cognitive-behavior therapy have shown the best evidence. Ondansetron, memantine, riluzole, clomipramine, mirtazapine and repetitive transcranial magnetic stimulation over supplementary motor area show some preliminary evidence. Ablative neurosurgery or deep brain stimulation may be tried in carefully selected treatment refractory patients.

Decoding multiple sclerosis: an update on genomics and future directions

Abstract: A wealth of data confirms that genetic variation is an important determinant of multiple sclerosis (MS) risk. Population, family and molecular studies provide strong empirical support for a polygenic model of inheritance, driven primarily by allelic variants relatively common in the general population. The major histocompatibility complex (MHC) in chromosome 6p21.3 represents by far the strongest MS susceptibility locus genome-wide and was unambiguously identified in all studied populations. The primary signal arises from the HLA-DRB1 gene in the Class II segment of the locus, with hierarchical allelic and haplotypic effects. Independent protective signals in the telomeric Class I region of the locus have been described as well. Over the last 6 years, large multicenter DNA collections have thrived and the development of new laboratory and analytical approaches has matured at a remarkable pace, allowing pursuit of comprehensive 'agnostic' genome-wide association studies to identify and characterise the non-MHC genetic component of MS. Taken together, the results have provided unambiguous evidence for the association of over 100 non-MHC loci with disease susceptibility. Follow-up experiments refined some of the association signals (IL2RA and CD58), identified gene-gene interactions (HLA-DRB1/EVI5) and revealed mechanistic insights into the functional consequences of the identified gene variants, most notably an increase in the soluble to membrane-bound ratio for IL-7, IL-2 and TNF receptors and a tyrosine-protein kinase 2-mediated immune deviation. These results significantly broaden our understanding of disease pathogenesis and permit, for the first time, modeling an individual's disease risk within the context of his or her familial history. Progress in identifying additional risk alleles is likely to be rapid in the near future. Although the effect of any given predisposing variant is modest, the possibility exists that multifaceted gene-gene and/or gene-environment interactions could substantially increase the contribution of some variants to the overall genetic risk. In addition, susceptibility genes may be subject to epigenetic modifications, which greatly increase the complexity of MS inheritance. Despite these remarkable advances, the knowledge of MS genetics remains incomplete. For example, a key but unresolved question is whether genetic variants influence disease trajectory. Ongoing efforts to fully characterize the repertoire of genes that predispose to MS and modulate its presentation is discussed. Functional characterization of even a moderate genetic effect on MS pathogenesis by a known gene or group of genes can assist in elucidating fundamental mechanisms of disease expression and yield important therapeutic opportunities.

Epstein–Barr virus and multiple sclerosis: association or causation?

Abstract: Multiple sclerosis (MS) is a multifactorial disease in which both genetic and environmental factors and their interactions underlie causation. The current evidence base supports a strong association between Epstein-Barr virus (EBV) and MS, but potential causality remains strongly debated. It is not possible to exclude the possibility that an abnormal response to EBV infection is a consequence, rather than a cause, of the underlying pathophysiology of MS, or indeed that the association may be a reflection of a similar underlying disease mechanism. Substantial experimental progress is necessary to achieve consistency of molecular findings to complement the strong epidemiological association between EBV and MS, which cannot alone show causation. Collectively, the strength of the association between EBV and MS warrants careful development and trial of anti-EBV drugs to observe any effect on MS disease course.

Genetics of attention-deficit/hyperactivity disorder: current findings and future directions

Abstract: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting 5.29% of children worldwide. It presents a heterogeneous clinical expression, and both environmental and genetic factors are involved in the etiology. Despite high heritability estimates, identification of genes that confer susceptibility to ADHD has been a slow and difficult process. The first genetic studies targeted dopaminergic genes, but the effects were small and only explained a small portion of ADHD heritability. Recent studies focus on the identification of novel genes and pathways that may underlie ADHD. The main goal of this review is to present evidence from genome-wide association, copy number variation and family-based studies of genetic susceptibility to ADHD. The challenges involved to disclose ADHD susceptibility genes will be reviewed in order to provide directions for future studies.

Unraveling the mechanisms underlying postural instability in Parkinson's disease using dynamic posturography.

Abstract: Postural instability, one of the cardinal symptoms of Parkinson’s disease (PD), has devastating consequences for affected patients. Better strategies to prevent falls are needed, but this calls for an improved understanding of the complex mechanisms underlying postural instability. We must also improve our ability to timely identify patients at risk of falling. Dynamic posturography is a promising avenue to achieve these goals. The latest moveable platforms can deliver ‘real-life’ balance perturbations, permitting study of everyday fall circumstances. Dynamic posturography studies have shown that PD patients have fundamental problems in scaling their postural responses in accordance with the need of the actual balance task at hand. On-going studies evaluate the predictive ability of impaired posturography performance for daily life falls. We also review recent work aimed at exploring balance correcting steps in PD, and the presumed interaction between startle pathways and postural responses.

Treating multiple sclerosis with monoclonal antibodies: a 2013 update

Abstract: The third part of this in-depth review series on the treatment of multiple sclerosis (MS) with monoclonal antibodies covers the years 2010–2012. The natalizumab section gives a progressive multifocal leukoencephalopathy update, focusing on clinically relevant aspects. Furthermore, it outlines problems around natalizumab cessation and current evidence on therapeutic strategies thereafter. Finally, it reviews evidence on Janus-faced modes of natalizumab action besides anti-inflammatory effects, including proinflammatory effects. The section on alemtuzumab critically analyzes recent Phase III results and discusses which patients might be best suited for alemtuzumab treatment, and reviews the long-term immunological impact of this anti-CD52 antibody. The daclizumab section critically summarizes results from the Phase IIb SELECT/SELECTION trial and introduces the Phase III program. The section on anti-CD20 antibodies reviews Phase II results on ocrelizumab and ofatumumab, and discusses current perspectives of ...

Losses and gains: chronic pain and altered brain morphology

Abstract: As in many fields of neuroscience, alterations in brain morphology, and specifically gray matter volume and cortical thickness, have been repeatedly linked to chronic pain disorders. Numerous studies have shown changes in cortical and subcortical brain regions suggesting a dynamic process that may be a result of chronic pain or contributing to a more generalized phenomenon in chronic pain including comorbid anxiety and depression. In this review, we provide a perspective of pain as an innate state of pain based on alterations in structure and by inference, brain function. A better neurobiological understanding of gray matter changes will contribute to our understanding of how structural changes contribute to chronic pain (disease driver) and how these changes may be reversed (disease modification or treatment).

Understanding the relationship between smoking and pain

Abstract: This review provides an overview of evidence regarding several key mechanisms pertinent to understanding the co-occurrence of smoking dependence and pain, both potentially costly conditions, and highlights treatment implications and future research directions. We describe each of pain and smoking dependence and introduce a revised integrative reciprocal model that explains their co-occurrence. We then provide a selective review of evidence pertinent to direct and indirect pathways between variables postulated in the model. We also provide general recommendations for improving assessment and treatment of smokers with clinically significant pain. We conclude with a targeted agenda for future investigation of the co-occurrence of smoking and pain. Empirical efforts directed at testing postulates of the proposed integrative model may yield a better understanding of the nature of the relationship between these prevalent and costly health conditions as well as evidence-based preventive and treatment strategies for people who experience nicotine dependence and pain-related disability.

mTOR inhibitors as a new therapeutic option for epilepsy

Abstract: Dysregulation of the mTOR signaling pathway is associated with highly epileptogenic conditions such as tuberous sclerosis, focal cortical dysplasia, hemimegalencephaly and ganglioglioma, grouped under the term of 'mTORopathies'. Brain abnormalities associated with mTOR overactivation include enlarged and dysplastic neurons, abnormal cortical organization and astrogliosis. mTOR signaling intervenes in several molecular/biochemical processes leading to epileptogenesis. Animal models demonstrated that mTOR inhibitors could exert both an anticonvulsant action and an antiepileptogenic effect in models of genetic and acquired epilepsy. Preliminary studies in patients affected by tuberous sclerosis and treated with rapamycin or everolimus demonstrated potential benefits in seizure frequency reduction, suggesting that mTOR inhibition could be a promising treatment option for mTORopathies-related epilepsy. The authors reviewed the current knowledge of mTOR overactivation in different forms of epilepsy, and discuss the potential clinical use of mTOR inhibitors.

Revelation in the neuroprotective functions of rasagiline and selegiline: the induction of distinct genes by different mechanisms.

Abstract: In Parkinson's disease, cell death of dopamine neurons in the substantia nigra progresses and neuroprotective therapy is required to halt neuronal loss. In cellular and animal models, selegiline [(-)deprenyl] and rasagiline, inhibitors of type B monoamine oxidase (MAO)-B, protect neuronal cells from programmed cell death. In this paper, the authors review their recent results on the molecular mechanisms by which MAO inhibitors prevent the cell death through the induction of antiapoptotic, prosurvival genes. MAO-A mediates the induction of antiapoptotic bcl-2 and mao-a itself by rasagiline, whereas a different mechanism is associated with selegiline. Rasagiline and selegiline preferentially increase GDNF and BDNF in nonhuman primates and Parkinsonian patients, respectively. Enhanced neurotrophic factors might be applicable to monitor the neurorescuing activity of neuroprotection.

Advances in the management of multiple sclerosis spasticity: multiple sclerosis spasticity guidelines

Abstract: Symptomatic therapy of multiple sclerosis (MS) is an important part of a comprehensive treatment plan that aims to improve patients' quality of life. In the current era of medical progress, several factors have led to the development of guidelines for MS management. There is continued need for an evidence-based approach supported by high-quality data from controlled clinical trials. Most healthcare systems require this approach and include it in the reimbursement process. Guidelines are usually committed by national or continental neurological societies. The Spanish Society of Neurology demyelinating diseases working group has developed a consensus document on spasticity in patients with MS. MS experts from the group used the metaplan method to sum up the most important recommendations about spasticity for inclusion in the guidance. Recommendations were classified according to the Scottish Intercollegiate Guidelines Network system and approved by all members of the group. In Germany, the guideline panel o...