Molecular Nerve Repair : The molecular properties of the injured peripheral nerve and the application of viral vectors to enhance regeneration

Verhaagen, J. [Promotor]Malessy, M.J.A. [Copromotor]Boer, G.J. [Copromotor

Managing psychogenic pseudosyncope: Facts and experiences

Psychogenic pseudosyncope (PPS) is a common cause of apparent transient loss of conscious­ness (TLOC) with a dramatic impact on the quality of life. This review aims to give an overview of the definition, incidence, etiology, diagnosis, treatment, and prognosis of PPS based on a combination of literature data and personal experience. The limited literature on the subject suggests that PPS is relatively common but insufficiently recognized. PPS is probably similar to psychogenic nonepiteptic seizures (PNES), in which a long delay to diagnosis worsens the prognosis. A detailed history is of paramount importance for the diagnosis. The key feature in the history of patients with PPS is the occurrence of frequent, long attacks of apparent TLOC with closed eyes. The diagnosis is certain when a typical event is recorded during a tilt-table test with simultaneous blood pressure (BP), heart rate and video-electroencephalographic re­cordings. Home video and BP recording during an attack can be very useful. The diagnosis should be communicated to the patient in a way that is clear, understandable and does not cause offense. Although treatment options have not been investigated formally, the literature on PNES suggests that cognitive behavioral therapy is beneficial

Fatigue in patients with myasthenia gravis. a systematic review of the literature

Myasthenia Gravis (MG) is a chronic autoimmune disease affecting the neuromuscular junction. Although a hallmark of MG is muscle fatigability due to dysfunction of the neuromuscular junction (peripheral fatigue), a large number of MG patients also report symptoms of central fatigue, defined as an experienced lack of energy, physically and/or mentally. We systematically reviewed the literature on all aspects of central fatigue in MG. Results were categorized in 5 domains: prevalence, diagnosis, pathophysiology, treatment or impact. The prevalence of patient-reported fatigue varies between 42 and 82%, which is significantly higher than in control subjects. Fatigue severity is usually assessed with standardized questionnaires, but the choice of questionnaire varies widely between studies. The pathophysiology of fatigue is unknown, but it is strongly associated with depressive symptoms, female gender and disease severity. Fatigue is also highly prevalent in ocular MG and patients in remission, suggesting a multifactorial origin. Fatigued MG patients have a lower quality of life. Pharmacological treatment of MG is associated with improvement of fatigue and promising results have been found with physical and psychological training programs. Fatigue is a highly prevalent symptom of MG with a severe negative impact on quality of life. Physicians treating patients with MG should be aware of this symptom, as it may be treatable with physical or psychological training programs. (c) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license. ( http://creativecommons.org/licenses/by/4.0/ )Neurological Motor Disorder

Lowering the cutoff value for increment increases the sensitivity for the diagnosis of Lambert-Eaton myasthenic syndrome

Background: Increment of compound muscle action potential amplitude is a diagnostic hallmark of Lambert-Eaton myasthenic syndrome (LEMS). Making a diagnosis can be challenging, therefore, a proper cutoff for abnormal increment is highly relevant for improved recognition

Prevalence and associated factors of fatigue in autoimmune myasthenia gravis

Fatigue is usually defined as a subjective perception of lacking energy, mentally or physically, with a difficulty sustaining voluntary activities. It is a common symptom of many diseases and most likely has a multifactorial cause. In myasthenia gravis (MG), fatigue has a high prevalence and is correlated with female sex and disease severity. However, no large scale studies have been performed. Therefore, we aimed to evaluate fatigue in the Dutch participants (n = 420) of the Dutch-Belgian Myasthenia Patient Registry using an online survey. Additional information was obtained on mood, sleep, coping, quality of life, disease severity, physical activities and medication. Severe fatigue was present in 62% with a mean score of 37.1 +/- 13.2 points. Fatigue severity and prevalence increased significantly with disease severity. A positive correlation was found for female gender, BMI, disease severity and depressive symptoms. A negative correlation was found for strenuous physical activities and older age. The strong association with disease severity suggests that fatigue should be recognized as an element of the symptomatology of MG. The observed association between strenuous activity and fatigue and differences in coping style between fatigued and non-fatigued patients warrant future clinical trials on exercise and cognitive behavioral therapy. (C) 2021 The Authors. Published by Elsevier B.V.Neurological Motor Disorder

Pharmacological treatment of Lambert-Eaton Myasthenic Syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is a very rare antibody-mediated autoimmune disease of the neuromuscular junction. Therapy can be divided in symptomatic treatment and immunosuppressive treatment. Symptomatic treatment with amifampridine is the only therapy currently authorized for use in LEMS patients. In the Netherlands the first choice drug is amifampridine base in an extended release formulation instead of the currently authorized amifampridine phosphate. This formulation has lower costs and is possibly safer due to lower peak concentrations. Other therapy used in LEMS patients is prescribed off-label and is based on experience in patients with myasthenia gravis. In many cases pyridostigmine is added as symptomatic treatment. In almost half of patients immunosuppressive therapy is started, mostly corticosteroids with or without azathioprine. Intravenous immunoglobulins and plasma exchange are used as emergency treatment. Currently no randomized clinical trials with new therapies are ongoing or announced in patients with LEMS, although multiple new therapies for myasthenia gravis are being investigated. These future therapies can be differentiated in symptomatic and immunomodulating drugs. The immunomodulating drugs can be further differentiated in early stage drugs which target the B-cell, later stage drugs which target the circulating antibodies and targeted therapy which have a disease-specific target. Some early and later stage immunomodulating drugs show promising results in myasthenia gravis although high cost and uncertain long term safety may be limiting for incorporating these drugs in LEMS treatment guidelines. Clinical trials in LEMS patients are lacking due to the rarity of the disease and we suggest the following requirements for future trials of potential new treatments: Sufficient power by performing multicenter or n-of-1 trials when appropriate, a cross-over design to reduce the number of patients and using a LEMS-specific quantitative primary outcome measure like the 3TUG score

Walking Behavior Change Detector for a “Smart” Walker

AbstractThis study investigates the design of a novel real-time system to detect walking behavior changes using an accelerometer on a rollator. No sensor is required on the user. We propose a new non-invasive approach to detect walking behavior based on the motion transfer by the user on the walker. Our method has two main steps; the first is to extract a gait feature vector by analyzing the three-axis accelerometer data in terms of magnitude, gait cycle and frequency. The second is to classify gait with the use of a decision tree of multilayer perceptrons. To assess the performance of our technique, we evaluated different sampling window lengths of 1, 3 an 5seconds and four different Neural Network architectures. The results revealed that the algorithm can distinguish walking behavior such as normal, slow and fast with an accuracy of about 86%. This research study is part of a project aiming at providing a simple and non-invasive walking behavior detector for elderly who use rollators

Measuring CMAPs in addition to MEPs can distinguish peripheral ischemia from spinal cord ischemia during endovascular aortic repair

Objective: Spinal cord injury is a devastating complication after endovascular thoracic and thoracoabdominal aneurysm repair (EVAR). Motor evoked potentials (MEPs) can be monitored to detect spinal cord injury, but may also be affected by peripheral ischemia caused by femoral artery sheaths. We aimed to determine the incidence of peripheral ischemia during EVAR, and whether central and peripheral ischemia can be distinguished using compound muscle action potentials (CMAPs).Methods: We retrospectively analyzed all EVAR procedures between March 1st 2015 and January 1st 2020 during which MEPs were monitored. Peripheral ischemia was defined as both a reduction in MEP amplitudes reversed by removing the femoral sheaths and no clinical signs of immediate post-procedural paraparesis. All other MEP decreases were defined as central ischemia.Results: A significant MEP decrease occurred in 14/27 (52%) of all procedures. Simultaneous CMAP amplitude reduction was observed in 7/8 (88%) of procedures where peripheral ischemia occurred, and never in procedures with central ischemia.Conclusions: MEP reductions due to peripheral ischemia are common during EVAR. A MEP-reduction without a CMAP decrease indicates central ischemia.Significance: CMAP measurements can help to distinguish central from peripheral ischemia, potentially reducing the chance of misinterpreting of MEP amplitude declines as centrally mediated, without affecting sensitivity. (C) 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.Cardiovascular Aspects of Radiolog

Accuracy of patient-reported data for an online patient registry of autoimmune myasthenia gravis and Lambert-Eaton myasthenic syndrome

Disorders of the neuromuscular junction (NMJ) comprise a spectrum of rare diseases causing muscle fatigability and weakness, leading to life-long effects on quality of life. We established the Dutch-Belgian registry for NMJ disorders, based on a unique combination of patient -and physician-reported information. Information on natural course, disease burden, prevalence of complications and comorbidity is collected through patient-reported standardized questionnaires and verified using medical documentation. Currently, the registry contains information of 565 Myasthenia Gravis (MG) patients and 38 Lambert-Eaton myasthenic syndrome (LEMS) patients, constituting approximately 25% (MG) and 80% (LEMS) of patients in the Netherlands. This is a very large registry, with the highest participation rate per capita. In addition to confirming many disease characteristics previously described in the literature, this registry provides several novel insights. The reported rate of potentially corticosteroid-related comorbidity, including hypertension, heart disease, osteoporosis and type 2 diabetes was high, emphasizing the need to commence corticosteroid-sparing immune suppressive treatment as soon as possible. The reported rate of other auto-immune diseases is far higher than previously expected: 27% of MG and 38% of LEMS patients, and a surprisingly high number of MG patients (47%) is unaware of their antibody status. In conclusion, this registry provides a valuable collection of information regarding MG and LEMS disease course. Continuous collection of annual follow-up data will provide further longitudinal insights in disease burden, course and treatment effect. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )Neurological Motor Disorder