Mycophenolate (CellCept) treatment of myasthenia gravis, chronic inflammatory polyneuropathy and inclusion body myositis

We report favorable results of the long term use of mycophenolate in the treatment of three patients with myasthenia gravis (MG), two patients with chronic inflammatory demyelinating polyneuropathy (CIDP), one patient with secondary polymyositis (PM), and one patient with inclusion body myositis (IBM). Side effects were mild. Mycophenolate appears to be a useful addition to the armamentarium of immunosuppressants for treatment of chronic immunologically mediated neuromuscular diseases.     

The International Society for Bipolar Disorders (ISBD) consensus guidelines for the safety monitoring of bipolar disorder treatments

Objectives:  Safety monitoring is an important aspect of bipolar disorder treatment, as mood-stabilising medications have potentially serious side effects, some of which may also aggravate existing medical comorbidities. This paper sets out the International Society for Bipolar Disorders (ISBD) guidelines for the safety monitoring of widely used agents in the treatment of bipolar disorder. These guidelines aim to provide recommendations that take into consideration the balance between safety and cost-effectiveness, to highlight iatrogenic and preventive clinical issues, and to facilitate the broad implementation of therapeutic safety monitoring as a standard component of treatment for bipolar disorder.
Methods:  These guidelines were developed by an ISBD workgroup, headed by the senior author (MB), through an iterative process of serial consensus-based revisions. After this, feedback from a multidisciplinary group of health professionals on the applicability of these guidelines was sought to develop the final recommendations.
Results:  General safety monitoring recommendations for all bipolar disorder patients receiving treatment and specific monitoring recommendations for individual agents are outlined.
Conclusions:  These guidelines are derived from evolving and often indirect data, with minimal empirical cost-effectiveness data available to provide guidance. These guidelines will therefore need to be modified to adapt to different clinical settings and health resources. Clinical acumen and vigilance remain critical ingredients for safe treatment practice.     

Assessment of muscle function in pathology with surface electrode EMG

Surface electromyography (SEMG) had been and is still widely used in kinesiology and fatigue studies. Its use in routine clinical neurophysiology remains limited. Patients are requiring non-invasive EMG, which could also benefit to physicians and health care system looking for tools to evaluate muscle function in neuromuscular diseases as well as for therapeutic trials. This is the aim of our clinical studies. We apply SEMG envelope signal analysis acquired from maximal voluntary contractions, and the related compound muscle action potential (CMAP). These unspecific parameters cannot be used for neuromuscular diseases diagnosis, objective under study by many research teams. In nerve lesions follow-up studies, our SEMG procedure is related to motor clinical progression. We are currently evaluating it in chronic neuromuscular diseases. The respective contribution in neuromuscular disorders of the different neurophysiology techniques has still to be confirmed, and compared to force measurement by manual or quantitative testing, dynamometry, other suggested techniques (spectroscopy, imaging) as well as functional scales.     

Neuromuscular disease and anesthesia

Patients with neuromuscular disease pose many anesthetic challenges and are at greater risk for perioperative complications, including respiratory or cardiovascular dysfunction and pulmonary aspiration. Therefore, these patients require special precautions, including interdisciplinary communication between primary care physicians, neurologists, physiatrists, surgeons, and anesthesiologists. Preoperative evaluation and optimization of comorbid conditions is critical. These patients may have adverse response to neuromuscular blocking drugs and the reversal drugs (e.g., neostigmine). They should be used with caution and titrated based on objective neuromuscular monitoring. Drugs that potentiate neuromuscular blocking drugs should also be avoided or their doses limited if possible. The risk of malignant hyperthermia in certain neuromuscular diseases mandates avoidance of triggering agents such as succinylcholine and inhaled anesthetics. Patients with neuromuscular disease may also be sensitive to sedative‐hypnotics and opioids, which should be used judiciously. Finally, the postoperative period requires close monitoring due to increased risk of postoperative cardiorespiratory dysfunction. Muscle Nerve 48 : 451–460, 2013     

Recommendations for the diagnosis and management of Alzheimer's disease and other disorders associated with dementia: EFNS guideline

The aim of this international guideline on dementia was to present a peer-reviewed evidence-based statement for the guidance of practice for clinical neurologists, geriatricians, psychiatrists, and other specialist physicians responsible for the care of patients with dementia. It covers major aspects of diagnostic evaluation and treatment, with particular emphasis on the type of patient often referred to the specialist physician. The main focus is Alzheimer's disease, but many of the recommendations apply to dementia disorders in general. The task force working group considered and classified evidence from original research reports, meta-analysis, and systematic reviews, published before January 2006. The evidence was classified and consensus recommendations graded according to the EFNS guidance. Where there was a lack of evidence, but clear consensus, good practice points were provided. The recommendations for clinical diagnosis, blood tests, neuroimaging, electroencephalography (EEG), cerebrospinal fluid (CSF) analysis, genetic testing, tissue biopsy, disclosure of diagnosis, treatment of Alzheimer's disease, and counselling and support for caregivers were all revised when compared with the previous EFNS guideline. New recommendations were added for the treatment of vascular dementia, Parkinson's disease dementia, and dementia with Lewy bodies, for monitoring treatment, for treatment of behavioural and psychological symptoms in dementia, and for legal issues. The specialist physician plays an important role together with primary care physicians in the multidisciplinary dementia teams, which have been established throughout Europe. This guideline may contribute to the definition of the role of the specialist physician in providing dementia health care.     

Consensus treatment recommendations for late-onset Pompe disease

Introduction: Pompe disease is a rare, autosomal recessive disorder caused by deficiency of the glycogen‐degrading lysosomal enzyme acid alpha‐glucosidase. Late‐onset Pompe disease is a multisystem condition, with a heterogeneous clinical presentation that mimics other neuromuscular disorders. Methods: Objective is to propose consensus‐based treatment and management recommendations for late‐onset Pompe disease. Methods: A systematic review of the literature by a panel of specialists with expertise in Pompe disease was undertaken. Conclusions: A multidisciplinary team should be involved to properly treat the pulmonary, neuromuscular, orthopedic, and gastrointestinal elements of late‐onset Pompe disease. Presymptomatic patients with subtle objective signs of Pompe disease (and patients symptomatic at diagnosis) should begin treatment with enzyme replacement therapy (ERT) immediately; presymptomatic patients without symptoms or signs should be observed without use of ERT. After 1 year of ERT, patients' condition should be reevaluated to determine whether ERT should be continued. Muscle Nerve, 2012     

A review and commentary on a sample of 15 UK guidelines for the drug treatment of Alzheimer's disease.

BACKGROUND: There has been widespread development of clinical guidelines for the treatment of Alzheimer's disease since the introduction of donepezil in the UK in 1997. These have been developed nationally, regionally, locally and by independent groups. An independent review of guidelines available in the public domain was commissioned to provide an overview of the range and variability in the recommendations being made. METHODS: Fifteen sets of guidelines obtained from a variety of sources were reviewed in a standardized way to extract the recommendations being made in the following areas: diagnosis; investigations; the evidence base of the recommendations: initiation of drug treatment; monitoring and dose adjustment; and decision-making on maintenance or discontinuation of treatment. RESULTS: None of the documents fulfilled criteria for high-quality evidence-based guidelines. Substantial variability was evident in all areas of recommendation. All of the guidelines appeared to be based upon consensus opinion. Only one incorporated a statement of potential conflicts of interest affecting the working group who developed the guideline. CONCLUSIONS: The lack of consistency found in this sample of guidelines would inevitably lead to inequalities in the health care delivered in different areas. A national initiative is needed to encourage true evidence-based guideline development, not only on drug treatment but also on the wider issues raised such as diagnosis, investigations and the best treatment setting for delivering drug and other therapies.     

Access to physician treatment for a mental disorder: a regional analysis

  Background: This study examined (1) disparities in the proportion of persons who accessed a physician for treatment of a diagnosed mental disorder across 17 health regions in Alberta, Canada, and (2) the extent to which regional disparities in physician access could be explained by differences in regional demographies, population needs, or physician supply. Methods: The study illustrates the use of ecological comparisons for regional health system performance evaluations. Regional characteristics were aggregated from four sources of data: the health insurance registry file (population denominators and regional demographies), physician claims data (treatment access), census data (social indicators of population need), and the medical directory of the College of Physicians of Surgeons (physician supply). Results: Regional variability in needs-adjusted measures of access to physician-based treatment services were comparatively small (varying by a factor of 1.6). Models containing adjustments for demography, need, and physician supply explained 41% of regional variation in access. Of the total variation explained, physician supply explained a smaller proportion (39%) in comparison to social demography and needs (61%). Few large regional imbalances were noted when needs-adjusted and supply-adjusted estimates were compared. Only two areas appeared to be underserviced in comparison to their local needs, reflecting approximately 6% of the provincial population. Conclusions: While all three study factors proved important, findings support the broad conclusion that social demography and social risk (a proxy for need) will remain the key determinants predicting access to physician services for treatment of mental disorders in publicly funded health systems. Accepted: 28 September 1999     

Discrimination and systemic inflammation: A critical review and synthesis

Exposure to discrimination or unfair treatment has emerged as an important risk factor for illness and disease that disproportionately affects racial and ethnic minorities. Discriminatory experiences may operate like other stressors in that they activate physiological responses that adversely affect the maintenance of homeostasis. Research suggests that inflammation plays a critical role in the pathophysiology of stress-related diseases. Recent findings on discrimination and inflammation are discussed. We highlight limitations in the current evidence and provide recommendations for future studies that seek to examine the association between discrimination and inflammation.     

Prevention of homicidal behaviour in men with psychiatric disorders

Objectives. Homicide is overwhelmingly committed by men compared to women. Conservative estimates suggest that more than a third of these individuals have a treatable psychiatric disorder. These data present an opportunity to mental health clinicians to assist in the prevention of homicide by improving men's mental health. Methods. We review the current literature on men's mental health with a focus on assessing and reducing homicide risk in men with psychiatric conditions. Results. Bipolar disorder and schizophrenia appear to share a neural endophenotype that is a risk factor for homicide. Dual disorders, or the presence of a substance use disorder with other major mental illness, are a major risk factor for homicide in males. Dual diagnosis disorders, personality disorders and pathological traits and male depression share emotion dysregulation, irritability, and reactive aggression. Promoting physician education, addressing firearm safety, reducing the reluctance of men relative to women to engage in help-seeking behaviour, and using targeted risk interviews which integrate these data are all currently recommended. Conclusions. The main focus in prevention of homicidal behaviour in males with psychiatric disorders should be to identify high risk groups, to provide adequate treatment, and to facilitate compliance with long-term treatment while considering male specific problems and needs.     

Guidelines for Screening of Extracranial Carotid Artery Disease: A Statement for Healthcare Professionals from the Multidisciplinary Practice Guidelines Committee of the American Society of Neuroimaging; Cosponsored by the Society of Vascular and Interventional Neurology

The aim of this new statement is to provide comprehensive and timely evidence-based recommendations on the screening for asymptomatic carotid artery stenosis in the general population and selected subsets of patients. Recommendations are included for high-risk persons in the general population; patients undergoing open heart surgery including coronary artery bypass surgery; patients with peripheral vascular diseases, abdominal aortic aneurysms, and renal artery stenosis; patients after radiotherapy for head and neck malignancies; patients following carotid endarterectomy, or carotid artery stent placement; patients with retinal ischemic syndromes; patients with syncope, dizziness, vertigo or tinnitus; and patients with a family history of vascular diseases and hyperhomocysteinemia. The recommendations are based on prevalence of disease, anticipated benefit, and concurrent guidelines from other professional organizations in selected populations.     

Immunosuppressive / immunomodulating therapies in myasthenia gravis-at present and in the near future

Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission that is primarily caused autoantibodies specific to the neuromuscular junction and is characterized by fatigability and weakness of the striated muscles. Immunosuppression is the mainstay of treatment for MG, and patients with MG are currently treated with immunomodulating or immunosuppressive agents. This review summarizes the current situation and perspective of medical therapy for MG, focusing on mechanisms of action and clinical application of corticosteroids and different classes of immunomodulating or immunosuppressive drugs used for MG. Immunosuppressive treatment is indicated for patients with disabling weakness, not sufficiently managed with cholinesterase inhibitors. Prednisolone (PSL) is used in the great majority of patients. Tacrolimus and cyclosporine are the first-line immunosuppressants, whereas azathioprine is a conventional but less frequently used medication in Japan. The incidence of late- and elderly-onset MG is reported to be increasing. The risk of complications in corticosteroid treatment appears to depend on drug dosage, treatment duration, and patients' characteristics, and the serious side effects should be increased in late- and elderly- onset MG. Although nonspecific, current immunosuppressive treatment is highly effective in most MG patients, the need for prolonged administration and unwanted effects are still relevant limitations to its use.     

Cross-national disparities contribute to heterogeneity in patient outcomes following invasive monitoring: A hierarchical mixed-effects analysis

There is substantial variability in outcomes following invasive monitoring and surgical treatment of drug-resistant epilepsy (DRE). Patients with DRE are uniquely vulnerable to cross-national health care disparities, as their epilepsy is difficult to treat and requires extensive resources. In a large cross-national database of patients undergoing invasive monitoring for epilepsy surgery, we sought to evaluate the association between social, economic, and educational indicators of the country of treatment and patient outcomes following invasive monitoring. We performed a mixed-effects analysis of an individual patient database of 595 subjects enrolled in 33 studies encompassing 25 neurosurgical centers in 10 countries of invasive monitoring for epilepsy from 1996 to 2019. Upon preliminary univariate analysis, significant nation-level predictors of seizure outcome following either stereoelectroencephalography or subdural electrodes were hospital beds per 100,000 population, physician density, gross domestic product (GDP) growth, male and female educational attainment, and unemployment rate. On multivariate mixed-effects logistic regression, physician density (β = −0.5112, P<.00697) and GDP growth (β = 0.53822, P<.00404) were the only nation-level covariates of significance associated with seizure outcome. A higher physician density was associated with lesser seizure freedom rates, whereas higher GDP growth was associated with greater seizure freedom rates. Although patient-specific variables were the primary determinant of seizure outcomes, cross-national disparities also contribute to heterogeneities. Our findings highlight the importance of a systems-level dialogue to improve surgical outcomes for DRE patients.     

Phenotype genotype analysis in 15 patients presenting a congenital myasthenic syndrome due to mutations in DOK7

Congenital myasthenic syndromes (CMSs) are a heterogeneous group of diseases caused by genetic defects affecting neuromuscular transmission. Mutations of DOK7 have recently been described in recessive forms of CMS. Dok-7 is a cytoplasmic post-synaptic protein co-activator of the muscle-specific receptor-tyrosine kinase (MuSK) involved in neuromuscular synaptogenesis and maintenance. We report clinical, morphological and molecular data on 15 patients with mutations in DOK7. Eleven different mutations (5 novel) were identified and all patients but one were found to carry at least the common c.1124_1127dupTGCC mutation. Patients with DOK7 mutations have a particular limb-girdle pattern, without tubular aggregates but a frequent lipidosis on the muscle biopsy. Changes in pre- and post-synaptic compartments of the neuromuscular junction were also observed in muscle biopsies: terminal axons showed defective branching which resulted in a unique terminal axon contacting en passant postsynaptic cups. Clinical features, muscle biopsy findings or response to therapy were confusing in several patients. Characterization of this distinct phenotype is essential to provide clues for targeted genetic screening and to predict the therapeutic response to anticholinesterase treatments or ephedrine as has been suggested.     

Neuromuscular ultrasound in common entrapment neuropathies

Neuromuscular ultrasound involves the use of high‐resolution ultrasound to image the peripheral nervous system of patients with suspected neuromuscular diseases. It complements electrodiagnostic studies well by providing anatomic information regarding nerves, muscles, vessels, tendons, ligaments, bones, and other structures that cannot be obtained with nerve conduction studies and electromyography. Neuromuscular ultrasound has been studied extensively over the past 10 years and has been used most often in the assessment of entrapment neuropathies. This review focuses on the use of neuromuscular ultrasound in 4 of the most common entrapment neuropathies: carpal tunnel syndrome, ulnar neuropathy at the elbow and wrist, and fibular neuropathy at the knee. Muscle Nerve 48:696–704, 2013     

Cardiac complications of childhood myopathies

The management of individuals with a neuromuscular disorder is usually focused on the skeletal muscle weakness and resulting complications, such as respiratory failure. Long-term prognosis of a number of neuromuscular conditions is, however, also determined by the type and severity of cardiac involvement. Early recognition and treatment of the cardiovascular complications are part of the task of the multidisciplinary team involved in the care of these patients. Although for several of the common conditions, there is general consensus on the cardiac investigations and treatments, in the rarer disorders, evidence-based recommendations are not available, and suggestions from experts provide an acceptable solution. This review summarizes the recent advances in our understanding of the pathogenesis and phenotypic diversity of cardiac complications associated with pediatric myopathies and provides a rational framework for planning the monitoring and therapeutic intervention in individual conditions.     

Report of Recommendations: The Annapolis Coalition Conference on Behavioral Health Work Force Competencies

In May 2004, the Annapolis Coalition on Behavioral Health Workforce Education convened a national meeting on the identification and assessment of competencies. The Conference on Behavioral Health Workforce Competencies brought leading consumer and family advocates together with other experts on competencies from diverse disciplines and specialties in the fields of both mental health care and substance use disorders treatment. Aided by experts on competency development in business and medicine, conference participants have generated 10 consensus recommendations to guide the future development of workforce competencies in behavioral health. This article outlines those recommendations. A collaborative effort to identify a set of core or common competencies is envisioned as a key strategy for advancing behavioral health education, training, and other workforce development initiatives.This work was supported in part by Contract No. 03M00013801D from the Substance Abuse and Mental Health Services Administration.     

Therapeutic effects of PEGylated insulin-like growth factor I in the pmn mouse model of motoneuron disease

Based on its potent neurotrophic and myotrophic activities, insulin-like growth factor I (IGF-I) has been proposed for treatment of neuromuscular disorders such as muscular dystrophies and amyotrophic lateral sclerosis (ALS). However, the short half life in the circulation limits its use in vivo. At least in mouse models, beneficial effects are generally only observed by dosing regimens such as minipumps or gene therapy that are difficult to translate to patients. We have developed a polyethylene glycol coupled IGF-I (PEG-IGF-I) that could circumvent these problems by longer half-life, showing all features of a therapeutic agent supporting muscular and neuronal function. Here we investigated its effects in the pmn mutant mouse, a model with typical dying-back motoneuron degeneration. In vitro, PEG-IGF-I and rhIGF-I profoundly promoted survival axonal growth of wild-type as well as pmn mutant embryonic motoneurons, suggesting that PEG-IGF-I had a fully conserved neurotrophic activity via its receptor. In vivo, treatment of pmn mutant mice with PEG-IGF-I prolonged survival, protected against late stage weight loss and significantly maintained muscle force and motor coordination. Consistently, PEG-IGF-I treatment rescued facial and lumbar motoneurons from cell death and partially preserved phrenic nerve myelinated axons. The data support that PEG-IGF-I could be used for treatment of neuromuscular diseases in a clinically feasible manner.     

Treating depression in substance abusers

The literature on the diagnosis and treatment of depression is reviewed to arrive at recommendations for clinical practice, future research, and models of service delivery. The DSM-IV criteria are found to provide a sound basis for diagnosis, and a review of placebocontrolled trials of antidepressant medications among substance-dependent patients suggests medication is effective in the setting of careful diagnosis, preferably during a currently observed abstinent period. Clinical recommendations offered for the approach to patients with co-occurring depression and substance dependence include the following: 1) Initiate treatment for substance dependence and encourage abstinence; 2) Conduct a careful psychiatric history and apply DSM-IV criteria for primary or substance-induced depression; 3) If depression meets diagnostic criteria and persists despite treatment of substance use disorder, treat the depression. Future research should include trials of psychotherapeutic or behavioral treatments, studies of treatment algorithms and of integrated systems of care, and studies of methods for disseminating diagnostic and treatment methods in an effort to diminish traditional boundaries between the skill sets of mental health and substance abuse clinicians.