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Valko Y, Wirth MA, Fierz FC, Schesny MK, Rosengren S, Schmückle-Meier T, Bockisch CJ, Straumann D, Schreiner B, Weber KP. Accuracy of Repetitive Ocular Vestibular-Evoked Myogenic Potentials to Diagnose Myasthenia Gravis in Patients With Ptosis or Diplopia. Neurology 2024; 102:e209395. [PMID: 38669629 PMCID: PMC11398977 DOI: 10.1212/wnl.0000000000209395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Accepted: 02/27/2024] [Indexed: 04/28/2024] Open
Abstract
BACKGROUND AND OBJECTIVES We developed repetitive ocular vestibular-evoked myogenic potentials (roVEMP) as an electrophysiologic test that allows us to elicit the characteristic decrement of extraocular muscles in patients with ocular myasthenia gravis (OMG). Case-control studies demonstrated that roVEMP reliably differentiates patients with OMG from healthy controls. We now aimed to evaluate the diagnostic accuracy of roVEMP for OMG diagnosis in patients with ptosis and/or diplopia. METHODS In this blinded prospective diagnostic accuracy trial, we compared roVEMP in 89 consecutive patients presenting with ptosis and/or diplopia suspicious of OMG with a multimodal diagnostic approach, including clinical examination, antibodies, edrophonium testing, repetitive nerve stimulation of accessory and facial nerves, and single-fiber EMG (SFEMG). We calculated the roVEMP decrement as the ratio between the mean of the first 2 responses compared with the mean of the sixth-ninth responses in the train and used cutoff of >9% (unilateral decrement) in a 30 Hz stimulation paradigm. RESULTS Following a complete diagnostic work-up, 39 patients (44%) were diagnosed with ocular MG, while 50 patients (56%) had various other neuro-ophthalmologic conditions, but not MG (non-MG). roVEMP yielded 88.2% sensitivity, 30.2% specificity, 50% positive predictive value (PPV), and 76.5% negative predictive value (NPV). For comparison, SFEMG resulted in 75% sensitivity, 56% specificity, 55.1% PPV, and 75.7% NPV. All other diagnostic tests (except for the ice pack test) also yielded significantly higher positive results in patients with MG compared with non-MG. DISCUSSION The study revealed a high sensitivity of 88.2% for roVEMP in OMG, but specificity and PPV were too low to allow for the OMG diagnosis as a single test. Thus, differentiating ocular MG from other neuro-ophthalmologic conditions remains challenging, and the highest diagnostic accuracy is still obtained by a multimodal approach. In this study, roVEMP can complement the diagnostic armamentarium for the diagnosis of MG. CLASSIFICATION OF EVIDENCE This study provides Class I evidence that in patients with diplopia and ptosis, roVEMP alone does not accurately distinguish MG from non-MG disorders. TRIAL REGISTRATION INFORMATION ClinicalTrials.gov: NCT03049956.
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Affiliation(s)
- Yulia Valko
- From the Neurology Department (Y.V., M.K.S., C.J.B., D.S., B.S., K.P.W.), Clinical Neuroscience Center, and Ophthalmology Department (M.A.W., F.C.F., T.S.-M., C.J.B., K.P.W.), University Hospital Zurich, University of Zurich, Switzerland; Neurology Department and Institute of Clinical Neurosciences (S.R.), Royal Prince Alfred Hospital, Camperdown; and Central Clinical School (S.R.), Faculty of Medicine and Health, University of Sydney, Australia
| | - Magdalena A Wirth
- From the Neurology Department (Y.V., M.K.S., C.J.B., D.S., B.S., K.P.W.), Clinical Neuroscience Center, and Ophthalmology Department (M.A.W., F.C.F., T.S.-M., C.J.B., K.P.W.), University Hospital Zurich, University of Zurich, Switzerland; Neurology Department and Institute of Clinical Neurosciences (S.R.), Royal Prince Alfred Hospital, Camperdown; and Central Clinical School (S.R.), Faculty of Medicine and Health, University of Sydney, Australia
| | - Fabienne C Fierz
- From the Neurology Department (Y.V., M.K.S., C.J.B., D.S., B.S., K.P.W.), Clinical Neuroscience Center, and Ophthalmology Department (M.A.W., F.C.F., T.S.-M., C.J.B., K.P.W.), University Hospital Zurich, University of Zurich, Switzerland; Neurology Department and Institute of Clinical Neurosciences (S.R.), Royal Prince Alfred Hospital, Camperdown; and Central Clinical School (S.R.), Faculty of Medicine and Health, University of Sydney, Australia
| | - Marianne K Schesny
- From the Neurology Department (Y.V., M.K.S., C.J.B., D.S., B.S., K.P.W.), Clinical Neuroscience Center, and Ophthalmology Department (M.A.W., F.C.F., T.S.-M., C.J.B., K.P.W.), University Hospital Zurich, University of Zurich, Switzerland; Neurology Department and Institute of Clinical Neurosciences (S.R.), Royal Prince Alfred Hospital, Camperdown; and Central Clinical School (S.R.), Faculty of Medicine and Health, University of Sydney, Australia
| | - Sally Rosengren
- From the Neurology Department (Y.V., M.K.S., C.J.B., D.S., B.S., K.P.W.), Clinical Neuroscience Center, and Ophthalmology Department (M.A.W., F.C.F., T.S.-M., C.J.B., K.P.W.), University Hospital Zurich, University of Zurich, Switzerland; Neurology Department and Institute of Clinical Neurosciences (S.R.), Royal Prince Alfred Hospital, Camperdown; and Central Clinical School (S.R.), Faculty of Medicine and Health, University of Sydney, Australia
| | - Tanja Schmückle-Meier
- From the Neurology Department (Y.V., M.K.S., C.J.B., D.S., B.S., K.P.W.), Clinical Neuroscience Center, and Ophthalmology Department (M.A.W., F.C.F., T.S.-M., C.J.B., K.P.W.), University Hospital Zurich, University of Zurich, Switzerland; Neurology Department and Institute of Clinical Neurosciences (S.R.), Royal Prince Alfred Hospital, Camperdown; and Central Clinical School (S.R.), Faculty of Medicine and Health, University of Sydney, Australia
| | - Christopher J Bockisch
- From the Neurology Department (Y.V., M.K.S., C.J.B., D.S., B.S., K.P.W.), Clinical Neuroscience Center, and Ophthalmology Department (M.A.W., F.C.F., T.S.-M., C.J.B., K.P.W.), University Hospital Zurich, University of Zurich, Switzerland; Neurology Department and Institute of Clinical Neurosciences (S.R.), Royal Prince Alfred Hospital, Camperdown; and Central Clinical School (S.R.), Faculty of Medicine and Health, University of Sydney, Australia
| | - Dominik Straumann
- From the Neurology Department (Y.V., M.K.S., C.J.B., D.S., B.S., K.P.W.), Clinical Neuroscience Center, and Ophthalmology Department (M.A.W., F.C.F., T.S.-M., C.J.B., K.P.W.), University Hospital Zurich, University of Zurich, Switzerland; Neurology Department and Institute of Clinical Neurosciences (S.R.), Royal Prince Alfred Hospital, Camperdown; and Central Clinical School (S.R.), Faculty of Medicine and Health, University of Sydney, Australia
| | - Bettina Schreiner
- From the Neurology Department (Y.V., M.K.S., C.J.B., D.S., B.S., K.P.W.), Clinical Neuroscience Center, and Ophthalmology Department (M.A.W., F.C.F., T.S.-M., C.J.B., K.P.W.), University Hospital Zurich, University of Zurich, Switzerland; Neurology Department and Institute of Clinical Neurosciences (S.R.), Royal Prince Alfred Hospital, Camperdown; and Central Clinical School (S.R.), Faculty of Medicine and Health, University of Sydney, Australia
| | - Konrad P Weber
- From the Neurology Department (Y.V., M.K.S., C.J.B., D.S., B.S., K.P.W.), Clinical Neuroscience Center, and Ophthalmology Department (M.A.W., F.C.F., T.S.-M., C.J.B., K.P.W.), University Hospital Zurich, University of Zurich, Switzerland; Neurology Department and Institute of Clinical Neurosciences (S.R.), Royal Prince Alfred Hospital, Camperdown; and Central Clinical School (S.R.), Faculty of Medicine and Health, University of Sydney, Australia
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Bahadoram M, Mohammadianinejad SE, Akade E, Ahadi S, Rasras S. A Focus on Myasthenic Ptosis: The Interface of Medical and Surgical Treatment. World J Plast Surg 2024; 13:23-32. [PMID: 39665010 PMCID: PMC11629770 DOI: 10.61186/wjps.13.3.23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 11/03/2024] [Indexed: 12/13/2024] Open
Abstract
Ocular ptosis, or drooping of the upper eyelid, has diverse etiologies, including neurologic and non-neurologic causes. Aponeurotic ptosis is a common cause in the elderly and traumatic or mechanical causes can affect any age, mimicking a neurologic cause. The neurologic causes are diverse but especially arise peripherally from pathologies affecting the nerve, neuromuscular junction, and muscles. The choice of treatment depends on the particular cause, but surgical intervention can also be an option in appropriately selected neurological patients whose ptosis remains embarrassing despite the best medical treatment. Myasthenia gravis, an autoimmune disorder targeting the neuromuscular junction, is a significant cause of ocular ptosis. The treatment is mainly by symptomatic and immunosuppressive medications, but surgical interventions, such as blepharoplasty, may be considered in some cases of socially embarrassing ptosis.
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Affiliation(s)
- Mohammad Bahadoram
- Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyed Ehsan Mohammadianinejad
- Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Esma’il Akade
- Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Shana Ahadi
- Department of Neurosurgery, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Saleh Rasras
- Department of Neurosurgery, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Oculomotor fatigability with decrements of saccade and smooth pursuit for diagnosis of myasthenia gravis. J Neurol 2023; 270:2743-2755. [PMID: 36856847 PMCID: PMC10129983 DOI: 10.1007/s00415-023-11611-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 02/03/2023] [Accepted: 02/04/2023] [Indexed: 03/02/2023]
Abstract
BACKGROUND AND OBJECTIVES As the efficacy of current diagnostic methods for myasthenia gravis (MG) remains suboptimal, there is ongoing interest in developing more effective diagnostic models. As oculomotor fatigability is one of the most common and diagnostic symptoms in MG, we aimed to investigate whether quantitative saccadic and smooth-pursuit fatigability analyses with video-oculography (VOG) are useful for diagnosis of MG. METHODS A convenience cohort of 46 MG patients was recruited prospectively, including 35 with ocular and 11 with generalized MG (mean age, 50.9 ± 14.5 years; 17 females); 24 healthy controls (HCs) (mean age, 50.6 ± 16.3 years; 13 females) also were enrolled. Seventy-five repetitive saccades and smooth pursuits were recorded in ranges of 20° (horizontal plane) and 15° (vertical plane) using a three-dimensional VOG system. Based on the oculomotor range of the second saccade and smooth pursuit and the mean ranges of the last five of each, the estimated decrements (%) reflecting oculomotor fatigability were calculated. RESULTS The baseline oculomotor ranges did not show significant difference between the MG and HCs groups. However, following repetitive saccades and pursuits, the oculomotor ranges were decreased substantially during the last five cycles compared to baseline in the MG group. No such decrements were observed in the HC group (p < 0.01, Mann-Whitney U test). Receiver operating characteristic (ROC) analysis revealed that repetitive vertical saccades yielded the best differentiation between the MG and HC groups, with a sensitivity of 78.3% and specificity of 95.8% when using a decrement with an amplitude of 6.4% as the cutoff. CONCLUSION This study presents an objective and reproducible method for measuring decrements of oculomotor ranges after repetitive saccadic and pursuit movements. Quantification of oculomotor fatigability using VOG could be a sensitive and specific diagnostic tool for MG and allows easy, cost-effective, accurate, and non-invasive measurements. CLASSIFICATION OF EVIDENCE This study provides class III evidence that VOG-based quantification of saccadic and pursuit fatigability accurately identifies patients with MG.
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Abstract
BACKGROUND Around 60%--75% of myasthenia gravis (MG) patients initially present with nonspecific ocular symptoms. Failed recognition of these symptoms may delay the diagnosis of MG up to 5 years or more, leading to a reduced likelihood of remission and increased morbidity. Current diagnostic tests are either poorly sensitive for patients presenting with ocular symptoms alone or are time consuming, invasive, require a high level of technical expertise, and generally are universally difficult to obtain. This review will explore quantitative eye and pupil tracking as a potential noninvasive, time-effective, and less technically demanding alternative to current diagnostic tests of MG. EVIDENCE ACQUISITION Comprehensive literature review. RESULTS Thirty-two publications using oculography for the diagnosis of MG and 6 studies using pupillometry were evaluated. In MG patients, extra ocular muscle fatigue was evident in reports of intersaccadic, intrasaccadic and postsaccadic abnormalities, changes in optokinetic nystagmus, slow eye movements, disconjugate saccades, and pupillary constrictor muscle weakness. CONCLUSIONS Our review identified several potentially useful variables that derive from oculography and pupillometry studies that could assist with a timely diagnosis of MG. Limitations of this review include heterogeneity in design, sample size, and quality of the studies evaluated. There is a need for larger, well-designed studies evaluating eye-tracking measures in the diagnosis of MG, especially for patients presenting with purely ocular symptoms.
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Bedside and laboratory diagnostic testing in myasthenia. J Neurol 2022; 269:3372-3384. [PMID: 35142871 PMCID: PMC9119875 DOI: 10.1007/s00415-022-10986-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/18/2022] [Accepted: 01/19/2022] [Indexed: 11/02/2022]
Abstract
Myasthenia gravis (MG) and congenital myasthenic syndromes (CMS) are a group of disorders with a well characterised autoimmune or genetic and neurophysiological basis. We reviewed the literature from the last 20 years assessing the utility of various neurophysiological, immunological, provocative and genetic tests in MG and CMS. Diagnostic sensitivity of repetitive nerve stimulation test ranges between 14 and 94% and specificity between 73 and 100%; sensitivity of single-fibre EMG (SFEMG) test ranges between 64 and 100% and specificity between 22 and 100%; anti-acetylcholine receptor (AChR) antibody sensitivity ranges from 13 to 97% and specificity ranges from 95 to 100%. Overall, SFEMG has the highest sensitivity while positive anti-AChR antibodies have the highest specificity. Newer testing strategies that have been investigated over the last couple of decades include ocular vestibular-evoked myogenic potentials, otoacoustic emissions and disease-specific circulating miRNAs in serum for autoimmune myasthenia, as well as next-generation sequencing for genetic testing of CMS. While there has been significant progress in developing newer testing strategies for diagnosing MG and CMS over the last couple of decades, more research is needed to assess the utility of these newer tools regarding their sensitivity and specificity.
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Pascuzzi RM, Bodkin CL. Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome: New Developments in Diagnosis and Treatment. Neuropsychiatr Dis Treat 2022; 18:3001-3022. [PMID: 36578903 PMCID: PMC9792103 DOI: 10.2147/ndt.s296714] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 11/24/2022] [Indexed: 12/24/2022] Open
Abstract
"Myasthenia Gravis is, like it or not, the neurologist's disease!" (Thomas Richards Johns II, MD Seminars in Neurology 1982). The most common disorders in clinical practice involving defective neuromuscular transmission are myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS). The hallmark of weakness related to malfunction of the neuromuscular junction (NMJ) is variability in severity of symptoms from minute to minute and hour to hour. Fatigable weakness and fluctuation in symptoms are common in patients whether the etiology is autoimmune, paraneoplastic, genetic, or toxic. Autoimmune MG is the most common disorder of neuromuscular transmission affecting adults with an estimated prevalence of 1 in 10,000. While LEMS is comparatively rare, the unique clinical presentation, the association with cancer, and evolving treatment strategies require the neurologist to be familiar with its presentation, diagnosis, and management. In this paper we provide a summary of the meaningful recent clinical developments in the diagnosis and treatment of both MG and LEMS.
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Affiliation(s)
- Robert M Pascuzzi
- Indiana University School of Medicine, Indiana University Health, Indianapolis, IN, USA
| | - Cynthia L Bodkin
- Indiana University School of Medicine, Indiana University Health, Indianapolis, IN, USA
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Warnecke T, Im S, Labeit B, Zwolinskaya O, Suntrup-Krüger S, Oelenberg S, Ahring S, Schilling M, Meuth S, Melzer N, Wiendl H, Ruck T, Dziewas R. Detecting myasthenia gravis as a cause of unclear dysphagia with an endoscopic tensilon test. Ther Adv Neurol Disord 2021; 14:17562864211035544. [PMID: 34394727 PMCID: PMC8361548 DOI: 10.1177/17562864211035544] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Accepted: 07/10/2021] [Indexed: 11/17/2022] Open
Abstract
Aims: The flexible endoscopic evaluation of swallowing-tensilon test (FTT) was developed to diagnose myasthenia gravis (MG) in patients with unclear pharyngeal dysphagia. The purpose of this study was to determine sensitivity and specificity of the FTT and compare its diagnostic validity with that of other diagnostic markers. Methods: In this single-centre pragmatic clinical cohort study, a total of 100 patients with unclear pharyngeal dysphagia were eligible to undergo FTT. All patients were subjected to FTT and subsequently followed up clinically. FTT was considered positive if a significant improvement of pharyngeal swallowing function could be objectified endoscopically upon administration of edrophonium chloride. In addition, repetitive nerve stimulation test and serum MG antibody analysis were conducted. Results: All subjects (mean age 62.5 ± 14.1 years, female 33) underwent FTT without any complications. According to the results of the diagnostic procedures and based on long-term clinical follow-up for at least 3 years, 51 patients were finally diagnosed with MG. The sensitivity and specificity for the FTT was 88.2% and 95.9%, respectively. Application of the Cochran’s Q test showed statistically significant heterogeneity among the diagnostic tests, with results indicating FTT performance to be more accurate than the repetitive nerve stimulation results (p < 0.001) and comparable with serum antibody tests (p > 0.99). Conclusion: FTT has excellent clinical properties to be used routinely in the assessment of dysphagia with isolated or predominant pharyngeal muscle involvement allowing rapid and accurate diagnosis of MG.
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Affiliation(s)
- Tobias Warnecke
- Department of Neurology with Institute of Translational Neurology, University of Muenster, Albert-Schweitzer-Campus 1, Building A1, Münster, 48149, Germany
| | - Sun Im
- Department of Rehabilitation Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Bendix Labeit
- Department of Neurology with Institute of Translational Neurology, University of Muenster, Muenster, Germany
| | - Olga Zwolinskaya
- Department of Neurology with Institute of Translational Neurology, University of Muenster, Muenster, Germany
| | - Sonja Suntrup-Krüger
- Department of Neurology with Institute of Translational Neurology, University of Muenster, Muenster, Germany
| | - Stephan Oelenberg
- Department of Neurology with Institute of Translational Neurology, University of Muenster, Muenster, Germany
| | - Sigrid Ahring
- Department of Neurology with Institute of Translational Neurology, University of Muenster, Muenster, Germany
| | - Matthias Schilling
- Department of Neurology with Institute of Translational Neurology, University of Muenster, Muenster, Germany
| | - Sven Meuth
- Department of Neurology, Heinrich-Heine University of Duesseldorf, Duesseldorf, Germany
| | - Nico Melzer
- Department of Neurology, Heinrich-Heine University of Duesseldorf, Duesseldorf, Germany
| | - Heinz Wiendl
- Department of Neurology with Institute of Translational Neurology, University of Muenster, Muenster, Germany
| | - Tobias Ruck
- Department of Neurology, Heinrich-Heine University of Duesseldorf, Duesseldorf, Germany
| | - Rainer Dziewas
- Department of Neurology and Neurorehabilitation, Hospital Osnabrueck, Osnabrueck, Germany
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Di Nicola MR, Pontara A, Kass GEN, Kramer NI, Avella I, Pampena R, Mercuri SR, Dorne JLCM, Paolino G. Vipers of Major clinical relevance in Europe: Taxonomy, venom composition, toxicology and clinical management of human bites. Toxicology 2021; 453:152724. [PMID: 33610611 DOI: 10.1016/j.tox.2021.152724] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Revised: 02/09/2021] [Accepted: 02/13/2021] [Indexed: 12/14/2022]
Abstract
Snakebites in Europe are mostly due to bites from Viperidae species of the genus Vipera. This represents a neglected public health hazard with poorly defined incidence, morbidity and mortality. In Europe, fourteen species of "true vipers" (subfamily Viperinae) are present, eleven of which belong to the genus Vipera. Amongst these, the main medically relevant species due to their greater diffusion across Europe and the highest number of registered snakebites are six, namely: Vipera ammodytes, V. aspis, V. berus, V. latastei, V. seoanei and V. ursinii. Generally speaking, viper venom composition is characterised by many different toxin families, like phospholipases A2, snake venom serine proteases, snake venom metalloproteases, cysteine-rich secretory proteins, C-type lectins, disintegrins, haemorrhagic factors and coagulation inhibitors. A suspected snakebite is often associated with severe pain, erythema, oedema and, subsequently, the onset of an ecchymotic area around one or two visible fang marks. In the field, the affected limb should be immobilised and mildly compressed with a bandage, which can then be removed once the patient is being treated in hospital. The clinician should advise the patient to remain calm to reduce blood circulation and, therefore, decrease the spread of the toxins. In the case of pain, an analgesic therapy can be administered, the affected area can be treated with hydrogen peroxide or clean water. However, anti-inflammatory drugs and disinfection with alcohol or alcoholic substances should be avoided. For each patient, clinical chemistry and ECG are always a pre-requisite as well as the evaluation of the tetanus immunisation status and for which immunisation may be provided if needed. The treatment of any clinical complication, due to the envenomation, does not differ from treatments of emergency nature. Antivenom is recommended when signs of systemic envenomation exist or in case of advanced local or systemic progressive symptoms. Recommendations for future work concludes. The aim of this review is to support clinicians for the clinical management of viper envenomation, through taxonomic keys for main species identification, description of venom composition and mode of action of known toxins and provide a standardised clinical protocol and antivenom administration.
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Affiliation(s)
| | - Andrea Pontara
- Internal Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - George E N Kass
- European Food Safety Authority, Scientific Committee and Emerging Risks unit, 43126 Parma, Italy
| | - Nynke I Kramer
- Institute for Risk Assessment Sciences, University of Utrecht, Utrecht, the Netherlands
| | - Ignazio Avella
- CIBIO/InBIO - Centro de Investigação em Biodiversidade e Recursos Genéticos da Universidade do Porto, Rua Padre Armando Quintas 7, 4485-661, Vairão, Portugal; Evolutionary and Translational Venomics Laboratory, Instituto de Biomedicina de Valencia - CSIC, Calle Jaime Roig 11, 46010, Valencia, Spain
| | - Riccardo Pampena
- Centro Oncologico ad Alta Tecnologia Diagnostica, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Italy
| | | | - Jean Lou C M Dorne
- European Food Safety Authority, Scientific Committee and Emerging Risks unit, 43126 Parma, Italy
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Prabhakar H, Ali Z. Intensive Care Management of the Neuromuscular Patient. TEXTBOOK OF NEUROANESTHESIA AND NEUROCRITICAL CARE 2019. [PMCID: PMC7120052 DOI: 10.1007/978-981-13-3390-3_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Neuromuscular emergencies are a distinct group of acute neurological diseases with distinct characteristic presentations. Patients who suffer from this group of diseases are at immediate risk of losing protection of their native airway as well as aspirating orogastric contents. This is secondary to weakness of the muscles of the oropharynx and respiratory muscles. Although some neuromuscular emergencies such as myasthenia gravis or Guillain-Barré syndrome are well understood, others such as critical illness myopathy and neuropathy are less well characterized. In this chapter, we have discussed the pathophysiology, diagnostic evaluation, and management options in patients who are admitted to the intensive care unit. We have also emphasized the importance of a thorough understanding of the use of pharmacological anesthetic agents in this patient population.
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Affiliation(s)
- Hemanshu Prabhakar
- Department of Neuroanaesthesiology and Critical Care, All India Institute of Medical Sciences, New Delhi, India
| | - Zulfiqar Ali
- Division of Neuroanesthesiology, Department of Anesthesiology, Sher-i-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir India
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Italian recommendations for diagnosis and management of congenital myasthenic syndromes. Neurol Sci 2018; 40:457-468. [PMID: 30554356 DOI: 10.1007/s10072-018-3682-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Accepted: 12/10/2018] [Indexed: 12/11/2022]
Abstract
Congenital myasthenic syndromes (CMS) are genetic disorders due to mutations in genes encoding proteins involved in the neuromuscular junction structure and function. CMS usually present in young children, but perinatal and adult onset has been reported. Clinical presentation is highly heterogeneous, ranging from mild symptoms to severe manifestations, sometimes with life-threatening respiratory episodes, especially in the first decade of life. Although considered rare, CMS are probably underestimated due to diagnostic difficulties. Because of the several therapeutic opportunities, CMS should be always considered in the differential diagnosis of neuromuscular disorders. The Italian Network on CMS proposes here recommendations for proper CMS diagnosis and management, aiming to guide clinicians in their practical approach to CMS patients.
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Im S, Suntrup-Krueger S, Colbow S, Sauer S, Claus I, Meuth SG, Dziewas R, Warnecke T. Reliability and main findings of the flexible endoscopic evaluation of swallowing-Tensilon test in patients with myasthenia gravis and dysphagia. Eur J Neurol 2018; 25:1235-1242. [PMID: 29802670 DOI: 10.1111/ene.13688] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2017] [Accepted: 05/22/2018] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND PURPOSE Diagnosis of pharyngeal dysphagia caused by myasthenia gravis (MG) based on clinical examination alone is often challenging. Flexible endoscopic evaluation of swallowing (FEES) combined with Tensilon (edrophonium) application, referred to as the FEES-Tensilon test, was developed to improve diagnostic accuracy and to detect the main symptoms of pharyngeal dysphagia in MG. Here we investigated inter- and intra-rater reliability of the FEES-Tensilon test and analyzed the main endoscopic findings. METHODS Four experienced raters reviewed a total of 20 FEES-Tensilon test videos in randomized order. Residue severity was graded at four different pharyngeal spaces before and after Tensilon administration. All interpretations were performed twice per rater, 4 weeks apart (a total of 160 scorings). Intra-rater test-retest reliability and inter-rater reliability levels were calculated. RESULTS The most frequent FEES findings in patients with MG before Tensilon application were prominent residues of semi-solids spread all over the hypopharynx in varying locations. The reliability level of the interpretation of the FEES-Tensilon test was excellent regardless of the rater's profession or years of experience with FEES. All four raters showed high inter- and intra-reliability levels in interpreting the FEES-Tensilon test based on residue clearance (kappa = 0.922, 0.981). The degree of residue normalization in the vallecular space after Tensilon application showed the highest inter- and intra-rater reliability level (kappa = 0.863, 0.957) followed by the epiglottis (kappa = 0.813, 0.946) and pyriform sinuses (kappa = 0.836, 0.929). CONCLUSION Interpretation of the FEES-Tensilon test based on residue severity and degree of Tensilon clearance, especially in the vallecular space, is consistent and reliable.
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Affiliation(s)
- S Im
- Department of Rehabilitation Medicine, Bucheon St Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheonshi, Korea
| | | | - S Colbow
- Department of Neurology, University of Münster, Münster, Germany
| | - S Sauer
- Department of Neurology, University of Münster, Münster, Germany
| | - I Claus
- Department of Neurology, University of Münster, Münster, Germany
| | - S G Meuth
- Department of Neurology, University of Münster, Münster, Germany
| | - R Dziewas
- Department of Neurology, University of Münster, Münster, Germany
| | - T Warnecke
- Department of Neurology, University of Münster, Münster, Germany
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12
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Myasthenia Gravis. Neuromuscul Disord 2018. [DOI: 10.1007/978-981-10-5361-0_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Abstract
Objective To examine whether or not an edrophonium challenge test is useful for diagnosing cervical dystonia. Patients We evaluated 10 patients with cervical dystonia and 10 with hemifacial spasms (disease controls). We administered edrophonium and saline in this double-blinded study. Before and after the injection, we recorded the participants' clinical signs using a video camera to assess the objective symptoms every two minutes. Ten minutes after the saline and edrophonium injections, participants evaluated their subjective clinical signs using a visual analog scale. The objective signs on the video recordings were scored by specialists who were blinded to the treatment. The mean visual analog scale scores were compared using the Wilcoxon rank-sum test for paired continuous variables. Results The clinical signs of participants with cervical dystonia were amplified by edrophonium. In contrast, the clinical signs in participants with hemifacial spasms were not affected by the edrophonium challenge test. Conclusion The edrophonium challenge test may be useful for diagnosing cervical dystonia.
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Affiliation(s)
| | - Nagahisa Murakami
- Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan
| | - Hidetaka Koizumi
- Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan
| | | | - Yuishin Izumi
- Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan
| | - Ryuji Kaji
- Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan
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Matsumoto S, Murakami N, Koizumi H, Takahashi M, Izumi Y, Kaji R. Edrophonium Challenge Test for Blepharospasm. Front Neurosci 2016; 10:226. [PMID: 27375406 PMCID: PMC4894005 DOI: 10.3389/fnins.2016.00226] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Accepted: 05/06/2016] [Indexed: 11/21/2022] Open
Abstract
Background: Blepharospasm is typically diagnosed by excluding any secondary diseases and neuropsychiatric disorders, as specific tests for blepharospasm are currently unavailable. Since anticholinergic agents are used to improve the symptoms of dystonia, we hypothesized that edrophonium chloride, an acetylcholinesterase inhibitor, may make the symptoms of dystonia more apparent. Therefore, we examined whether an edrophonium challenge test would be useful for diagnosing blepharospasm. Methods: We studied 10 patients with blepharospasm and 10 with hemifacial spasms (as disease controls). We administered edrophonium and saline in this double-blind study. Before and after the injection, we recorded the clinical signs using a video camera to assess the objective symptoms every 2 min. Ten minutes after the isotonic sodium chloride and edrophonium injections, the patients evaluated their subjective signs using a visual analog scale (VAS). The objective signs on the video recordings were scored by specialists who were blind to the treatment. Results: The subjective and objective signs of the patients with blepharospasm were amplified by edrophonium. In contrast, the signs in patients with hemifacial spasms were not changed by the edrophonium challenge test. Conclusions: The edrophonium challenge test may be used to diagnose blepharospasm. The study was registered with a ICMJE recognized registry, the UMIN-CTR, with the number UMIN000022557.
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Affiliation(s)
| | - Nagahisa Murakami
- Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School Tokushima, Japan
| | - Hidetaka Koizumi
- Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School Tokushima, Japan
| | | | - Yuishin Izumi
- Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School Tokushima, Japan
| | - Ryuji Kaji
- Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School Tokushima, Japan
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Abstract
PURPOSE OF REVIEW This article reviews the clinical presentations, diagnostic findings, and treatment options for autoimmune myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome. RECENT FINDINGS Immunologic research is unraveling the immunopathology of MG and identifying targets for novel immune-based therapy of this condition. MG patients with antibodies to muscle-specific tyrosine kinase (MuSK) frequently present with symptoms and clinical findings that suggest nerve or muscle disease. SUMMARY Early diagnosis and treatment have a marked effect on outcome in these diseases. In most cases, the diagnosis of MG or Lambert-Eaton myasthenic syndrome can be made from the history, supplemented with directed questions, and a physical examination designed to demonstrate variable weakness in affected muscle groups. Appropriate confirmatory tests almost always establish the diagnosis. Although several novel treatment modalities for MG are under investigation, currently available therapies produce substantial improvement in function and quality of life in most patients with this condition. Knowledge about the dosing, adverse effects, and costs of immunomodulatory therapies is essential for the effective management of patients with MG and Lambert-Eaton myasthenic syndrome.
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Golden SK, Reiff CJ, Painter CJ, Repplinger MD. Myasthenia Gravis Presenting as Persistent Unilateral Ptosis with Facial Droop. J Emerg Med 2015; 49:e23-5. [PMID: 25797936 DOI: 10.1016/j.jemermed.2015.01.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Revised: 01/03/2015] [Accepted: 01/05/2015] [Indexed: 11/19/2022]
Abstract
BACKGROUND Myasthenia gravis (MG) is an autoimmune neuromuscular disorder that is classically characterized by fluctuating weakness and fatigability of the ocular, bulbar, limb, or respiratory muscles. Over half of patients with MG will initially experience isolated ocular symptoms in one or both eyes. Most patients report that ocular symptoms are mild or undetectable upon awakening, and worsen throughout the day or with tasks such as driving. We describe an unusual case of MG presenting with an acute onset of persistent unilateral ptosis and ipsilateral facial droop without diurnal variation or other fluctuation in severity. CASE REPORT A 58-year-old man presented to the Emergency Department with a 3-day history of persistent, unilateral ptosis with facial droop, concerning for stroke. However, magnetic resonance imaging of the head found no evidence of stroke or any other central etiology. Routine laboratory testing was unremarkable. Neurology was consulted and they recommended sending acetylcholine receptor antibody tests. At the patient's subsequent neurology clinic visit, these tests were found to be abnormal. Electromyography was also done at this visit, confirming the diagnosis of MG. The patient subsequently underwent thymectomy and immunosuppressive therapy, with great improvement in his symptoms. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: MG may present as unilateral ptosis or facial drooping without the hallmark characteristic of fluctuating muscle weakness. Early diagnosis and subsequent treatment of MG improves long-term prognosis and remission rates. Emergency physicians should consider myasthenia gravis in cases of unilateral ocular symptoms after ruling out emergent central etiologies.
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Affiliation(s)
- Sean K Golden
- Department of Emergency Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Chris J Reiff
- Department of Emergency Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Chris J Painter
- Department of Emergency Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Michael D Repplinger
- Department of Emergency Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
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Arora Y, Li Y. Overview of myasthenia gravis. Hosp Pract (1995) 2013; 41:40-50. [PMID: 24145588 DOI: 10.3810/hp.2013.10.1079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
Myasthenia gravis is an antibody-mediated disorder of neuromuscular transmission that is characterized by weakness and fatigue of voluntary muscles. Weakness may be ocular, bulbar, or generalized. Diagnostic evaluation of patients consists of bedside assessment, antibody testing, and electrophysiologic studies. Various therapeutic options are available, which consist of anticholinesterase inhibitors for symptomatic management, immunosuppressive agents as maintenance therapy, and thymectomy. Plasmapheresis and intravenous immunoglobulin are used in patients in crisis or those with rapidly worsening or refractory symptoms. In our article, we elaborate on key aspects of the epidemiology, pathogenesis, diagnostic evaluation, and therapeutic options for patients with myasthenia gravis.
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Affiliation(s)
- Yeeshu Arora
- Division of the Neuromuscular Center, Department of Neurology, Cleveland Clinic, Cleveland, OH
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18
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Abstract
Acquired myasthenia gravis is a relatively uncommon disorder, with prevalence rates that have increased to about 20 per 100,000 in the US population. This autoimmune disease is characterized by muscle weakness that fluctuates, worsening with exertion, and improving with rest. In about two-thirds of the patients, the involvement of extrinsic ocular muscle presents as the initial symptom, usually progressing to involve other bulbar muscles and limb musculature, resulting in generalized myasthenia gravis. Although the cause of the disorder is unknown, the role of circulating antibodies directed against the nicotinic acetylcholine receptor in its pathogenesis is well established. As this disorder is highly treatable, prompt recognition is crucial. During the past decade, significant progress has been made in our understanding of the disease, leading to new treatment modalities and a significant reduction in morbidity and mortality.
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Rezania K, Goldenberg FD, White S. Neuromuscular Disorders and Acute Respiratory Failure: Diagnosis and Management. Neurol Clin 2012; 30:161-85, viii. [DOI: 10.1016/j.ncl.2011.09.010] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Abstract
Acquired myasthenia gravis (MG) is a chronic autoimmune disorder of the neuromuscular junction, characterized clinically by muscle weakness and abnormal fatigability on exertion. Current guidelines and recommendations for MG treatment are based largely on clinical experience, retrospective analyses and expert consensus. Available therapies include oral acetylcholinesterase (AChE) inhibitors for symptomatic treatment, and short- and long-term disease-modifying treatments. This review focuses on treatment of MG, mainly on the use of the AChE inhibitor pyridostigmine. Despite a lack of data from well controlled clinical trials to support their use, AChE inhibitors, of which pyridostigmine is the most commonly used, are recommended as first-line therapy for MG. Pyridostigmine has been used as a treatment for MG for over 50 years and is generally considered safe. It is suitable as a long-term treatment in patients with generalized non-progressive milder disease, and as an adjunctive therapy in patients with severe disease who are also receiving immunotherapy. Novel AChE inhibitors with oral antisense oligonucleotides have been developed and preliminary results appear to be promising. In general, however, AChE inhibitors provide only partial benefit and most patients eventually switch to long-term immunosuppressive therapies, most frequently corticosteroids and/or azathioprine. Although AChE inhibitors are known to be well tolerated and effective in relieving the symptoms of MG, further efforts are required to improve treatment options for the management of this disorder.
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Sanders DB. Approach to Diseases of the Neuromuscular Junction. Neuromuscul Disord 2011. [DOI: 10.1002/9781119973331.ch15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Romi F. Thymoma in myasthenia gravis: from diagnosis to treatment. Autoimmune Dis 2011; 2011:474512. [PMID: 21860784 PMCID: PMC3155972 DOI: 10.4061/2011/474512] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2011] [Accepted: 06/24/2011] [Indexed: 12/28/2022] Open
Abstract
One half of cortical thymoma patients develop myasthenia gravis (MG), while 15% of MG patients have thymomas. MG is a neuromuscular junction disease caused in 85% of the cases by acetylcholine receptor (AChR) antibodies. Titin and ryanodine receptor (RyR) antibodies are found in 95% of thymoma MG and 50% of late-onset MG (MG onset ≥50 years), are associated with severe disease, and may predict thymoma MG outcome. Nonlimb symptom profile at MG onset with bulbar, ocular, neck, and respiratory symptoms should raise the suspicion about the presence of thymoma in MG. The presence of titin and RyR antibodies in an MG patient younger than 60 years strongly suggests a thymoma, while their absence at any age strongly excludes thymoma. Thymoma should be removed surgically. Prethymectomy plasmapheresis/iv-IgG should be considered before thymectomy. The pharmacological treatment does not differ from nonthymoma MG, except for tacrolimus which is an option in difficult thymoma and nonthymoma MG cases with RyR antibodies.
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Affiliation(s)
- Fredrik Romi
- Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway
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23
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Abstract
This chapter covers the very large number of possible disorders that can affect the three ocular motor nerves, the neuromuscular junction, or the extraocular muscles. Conditions affecting the nerves are discussed under two major headings: those in which the site of damage can be anatomically localized (e.g., fascicular lesions and lesions occurring in the subarachnoid space, the cavernous sinus, the superior orbital fissure, or the orbit) and those in which the site of the lesion is either nonspecific or variable (e.g., vascular lesions, tumors, "ophthalmoplegic migraine," and congenital disorders). Specific comments on the diagnosis and management of disorders of each of the three nerves follow. Ocular motor synkineses (including Duane's retraction syndrome and aberrant regeneration) and disorders resulting in paroxysms of excess activity (e.g., neuromyotonia) are then covered, followed by myasthenia gravis and other disorders that affect the neuromuscular junction. A final section discusses disorders of the extraocular muscles themselves, including thyroid disease, orbital myositis, mitochondrial disease, and the muscular dystrophies.
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Affiliation(s)
- Christian J Lueck
- Department of Neurology, The Canberra Hospital, and Australian National University Medical School, Canberra, Australia.
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Myasthénies oculaires : diagnostic et traitement. Rev Neurol (Paris) 2010; 166:987-97. [DOI: 10.1016/j.neurol.2010.08.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2010] [Revised: 07/10/2010] [Accepted: 08/31/2010] [Indexed: 11/18/2022]
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Allen JA, Scala S, Jones HR. Ocular myasthenia gravis in a senior population: Diagnosis, therapy, and prognosis. Muscle Nerve 2009; 41:379-84. [DOI: 10.1002/mus.21555] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Abstract
Acquired myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction in which patients experience fluctuating skeletal muscle weakness that often affects selected muscle groups preferentially. The target of the autoimmune attack in most cases is the skeletal muscle acetylcholine receptor (AChR), but in others, non-AChR components of the neuromuscular junction, such as the muscle-specific receptor tyrosine kinase, are targeted. The pathophysiological result is muscle endplate dysfunction and consequent fatigable muscle weakness. Clinical presentations vary substantially, both for anti-AChR positive and negative MG, and accurate diagnosis and selection of effective treatment depends on recognition of less typical as well as classic disease phenotypes. Accumulating evidence suggests that clinical MG subgroups might respond differently to treatment. In this Review, we provide current information about the epidemiology, immunopathogenesis, clinical presentations, diagnosis, and treatment of MG, including emerging therapeutic strategies.
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Affiliation(s)
- Matthew N Meriggioli
- Department of Neurology and Rehabilitation, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
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Affiliation(s)
- G O Skeie
- Department of Neurology, Haukeland University Hospital, Bergen, Norway
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Punga AR, Sawada M, Stålberg EV. Electrophysiological signs and the prevalence of adverse effects of acetylcholinesterase inhibitors in patients with myasthenia gravis. Muscle Nerve 2008; 37:300-7. [PMID: 18069667 DOI: 10.1002/mus.20935] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
The aim of this prospective study was to assess whether extra discharges (EDs), sometimes following the compound muscle action potential, could be used as a neurophysiological indicator of overdose of acetylcholinesterase inhibitors (AChEIs) in patients with myasthenia gravis (MG). The characteristics and frequency of EDs were explored and the correlation of EDs with cholinergic side effects was also determined. Twenty-two MG patients (14 women, 8 men; 61 +/- 16 years of age) with daily AChEI treatment were examined. The mean disease duration was 10 years (range 2-62 years) and all patients had been treated with AChEI since MG onset. Both single and repetitive stimulation of the ulnar and accessory nerves were performed before and 60 min after oral pyridostigmine bromide (PB) administration and after additional edrophonium injection. Fatigue, side effects, and AChE activity in blood were assessed before and 60 min after PB intake. The daily dose of PB ranged from 150 to 900 mg/day. Fourteen patients (64%) experienced daily cholinergic adverse effects, and muscarinic side effects correlated with AChE activity. Eleven patients (50%) developed EDs after oral PB. Among the eight patients with daily nicotinic side effects, EDs were significantly (P < 0.05) more common. Additionally, older patients were more prone to develop cholinergic side effects and EDs. Thus, when EDs are found, patients should be asked about daily muscular symptoms, which may be related to AChEI treatment and not solely to MG.
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Affiliation(s)
- Anna Rostedt Punga
- Department of Clinical Neurophysiology, Uppsala University Hospital, 751 85 Uppsala, Sweden.
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Abstract
PURPOSE OF REVIEW Increasing rigor is being applied to medical decision making, but myasthenia gravis, commonly considered the best understood autoimmune disorder from a pathophysiological basis, lags other disciplines in the evidence base used to make clinical decisions. The review attempts to provide a focused, practical guideline for the diagnosis and treatment of ocular myasthenia within the limits of largely retrospective case series and expert opinion. RECENT FINDINGS Confirmation of clinical diagnosis continues to be challenging for ocular myasthenia. Despite the recognition of a new autoantigen, the muscle-specific kinase protein in generalized myasthenia gravis, it has been found to be only rarely identified in ocular myasthenia patients and therefore the majority of patients lack detectable autoantibodies and confirmation of a neuromuscular transmission disorder relies on specialized testing of single-fiber electromyography. The visual compromise of ocular myasthenia responds poorly to nonpharmacological and cholinesterase inhibitor therapy, and although corticosteroids are thought to be extremely effective, their toxicity is poorly defined in ocular myasthenia patients and whether they reduce the risk of development of generalized disease is not known. SUMMARY Rigorous clinical trials or large databases with outcome assessments are necessary in order to allow development of rational treatment strategies.
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Fiberoptic endoscopic evaluation of swallowing with simultaneous Tensilon application in diagnosis and therapy of myasthenia gravis. J Neurol 2008; 255:224-30. [PMID: 18217186 DOI: 10.1007/s00415-008-0664-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2007] [Revised: 05/04/2007] [Accepted: 05/30/2007] [Indexed: 10/22/2022]
Abstract
BACKGROUND Dysphagia is a common symptom in myasthenia gravis (MG). Clinical examination alone fails to detect and grade myasthenic dysphagia sufficiently. For a more precise examination of swallowing function in myasthenia gravis additional technical tools are necessary. OBJECTIVE To investigate the diagnostic and therapeutic impact of fiberoptic endoscopic evaluation of swallowing with simultaneous Tensilon application (FEES-Tensilon Test) in myasthenia gravis. METHODS FEES-Tensilon Test was performed following a standardized protocol. Four severely affected patients with dysphagia as their leading symptom were examined. Dysphagia was characterized by five salient endoscopic findings: leakage, delayed swallowing reflex, penetration, aspiration and residues. If a normalisation or at least an improvement of swallowing function occurred shortly after Tensilon administration the FEES-Tensilon Test was rated as being positive. RESULTS In three patients the FEES-Tensilon Test successfully detected MG-related dysphagia. In one patient with dysphagia caused by oculopharyngeal muscular dystrophy the FEES-Tensilon Test was truly negative. Beside an early diagnosis of MG-related dysphagia, the FEES-Tensilon Test was useful in the differentiation between myasthenic and cholinergic crisis and in guiding treatment decisions. In all patients the FEES-Tensilon Test was superior to clinical evaluation of dysphagia. No severe side effect occurred while performing the FEES-Tensilon Test. CONCLUSION The FEES-Tensilon Test is a suitable tool in the diagnosis and therapy of myasthenia gravis with pharyngeal muscles weakness.
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Chapter 13 Acquired Ocular Motility Disorders and Nystagmus. Neuroophthalmology 2008. [DOI: 10.1016/s1877-184x(09)70043-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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de la Calle Cabrera T, López Esteban P, Espínola Docio B, López Guinea A, García Teresa MA. [Juvenile myasthenia gravis. An overlooked disease by pediatricians]. An Pediatr (Barc) 2007; 66:422-3. [PMID: 17430725 DOI: 10.1157/13101253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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Abstract
BACKGROUND Although myasthenia gravis (MG) is often considered the best-understood autoimmune disorder and effective treatments have controlled life-threatening complications, the pathogenesis of ocular myasthenia (OM) remains enigmatic, and its clinical consequences offer therapeutic challenges. REVIEW SUMMARY About half of patients with MG present with visual complaints of droopy eyelids or double vision, and many will remain with purely ocular muscle weakness without generalized weakness, defined as OM. OM may be confused with disorders of the brainstem, ocular motor nerves, and eye muscles. Frustrating for the clinician, confirmatory tests such as the edrophonium test, serum acetylcholine receptor antibodies, and standard electrodiagnostic evaluations may fail to positively identify the clinical suspicion of OM. Patients may derive relief from nonpharmacologic interventions and cholinesterase inhibitors, but most will desire better symptom control with corticosteroids or need other immunosuppression. Early corticosteroid therapy may reduce the probability of generalization of the disease. The reasons for ocular muscle involvement by OM include physiologic and cellular properties of the ocular motor system and the unique immunology of OM, which, when better understood, will lead to novel treatments. CONCLUSIONS OM is a challenging disorder for the clinician and scientist, with both learning from the other for the betterment of the patient. The future requires answers to why the ocular muscles are so frequently involved by MG, whether the generalization of the disease may be limited by early corticosteroid treatment, and what treatment options may be developed which will improve symptoms without long-term complications.
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Affiliation(s)
- Linda L Kusner
- Department of Neurology, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA
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37
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Abstract
Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction that causes muscle weakness and fatigue. Fluctuating fatigue of skeletal muscles is the key clinical feature. Late-onset MG is more frequent in elderly men and is often misdiagnosed. While involvement of oropharyngeal musculature has been described with symptoms of dysphagia and slurred speech, the presence of fluctuating dysphonia as the first symptom of late-onset MG has not been emphasized. The case of an elderly man, who demonstrated voice changes and later swallowing impairment with weight loss, is reported. This case presentation of late-onset MG emphasizes that this form of the disease should be considered in the differential diagnosis of acute onset dysphonia in elderly persons.
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Affiliation(s)
- Manuel Montero-Odasso
- McGill Division of Geriatric Medicine, Jewish General Hospital, McGill University, Lady Davis Institute and Solidage Research Group, Montréal, QC, Canada.
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38
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Abstract
Disorders of the neuromuscular junction have a wide range of clinical presentations, which frequently poses a diagnostic challenge to evaluating clinicians. This article describes the tests used in the diagnosis of diseases of the neuromuscular junction, reviews the evidence supporting the use of each test, and proposes guidelines for their efficient utilization. A focused review of the literature was employed. Reports from four main categories of diagnostic tests (pharmacologic, electrodiagnostic, immunologic, and miscellaneous tests) were reviewed, and the sensitivity and specificity of each test in the diagnosis of specific neuromuscular junction diseases were examined. The clinical presentation determines which diagnostic tests should be utilized in individual cases of suspected neuromuscular junction disease. However, knowledge of the sensitivity and specificity of each test can help to focus the diagnostic evaluation and maximize the diagnostic yield of each test.
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Affiliation(s)
- Matthew N Meriggioli
- Department of Neurology and Rehabilitation, Section of Neuromuscular Disease, University of Illinois Medical Center, Chicago, Illinois, USA
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Abstract
AIM: To understand the correlation of serum cholinesterase (CHE) activity with gastric cancer and to assess their clinical significance.
METHODS: The velocity method was adopted to detect the activity of serum CHE in patients with gastric cancer and in patients with non-malignant tumor as controls.
RESULTS: The serum CHE activity in the treatment group was significantly lower than that in the control group with a very significant difference between the two groups (83.3:113.1,P = 0.0003). Age was significantly associated with the incidence of gastric caner.
CONCLUSION: Serum CHE activity has a close relation with the incidence of gastric cancer.
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Affiliation(s)
- Shan-Zhi Gu
- Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Medical College of of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China
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Abstract
BACKGROUND Diplopia is a common complaint in both inpatient and outpatient neurologic practice. Its causes are many, and special historical and examination features are important to localization and accurate diagnosis. REVIEW SUMMARY This review is divided into 2 sections: the first related to diagnosis and the second to treatment of binocular diplopia. In the diagnostic section, emphasis is placed on identification of historical and examination features that can help to differentiate diplopia caused by dysfunction of cranial nerves versus neuromuscular junction, or orbital extraocular muscle. Techniques available to the neurologist for examining ocular motility and ocular misalignment and focused laboratory testing to evaluate diplopia are discussed in detail. The final section covers the various treatments for binocular diplopia, with recommendations regarding the utility of each treatment for different types of diplopia. CONCLUSIONS A logical step-by-step approach applied to each patient with diplopia will help prevent misdiagnosis and improve patient care.
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Affiliation(s)
- Janet C Rucker
- Department of Neurology and Ophthalmology, Case Western Reserve School of Medicine, Cleveland, Ohio 44106, USA.
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41
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Abstract
We give an update on clinical, immunological, and therapeutic advances in the field of myasthenia gravis, including a summary of suggested therapeutic recommendations.
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Affiliation(s)
- F Romi
- Department of Neurology, Haukeland University Hospital, Bergen, Norway.
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42
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Abstract
Myasthenia gravis (MG) is a syndrome of fluctuating skeletal muscle weakness that worsens with use and improves with rest. Eye, facial, oropharyngeal, axial, and limb muscles may be involved in varying combinations and degrees of severity. Its etiology is heterogeneous, divided initially between those rare congenital myasthenic syndromes, which are genetic, and the bulk of MG, which is acquired and autoimmune. The autoimmune conditions are divided in turn between those that possess measurable serum acetylcholine receptor (AChR) antibodies and a smaller group that does not. The latter group includes those MG patients who have serum antibodies to muscle-specific tyrosine kinase (MuSK). Therapeutic considerations differ for early-onset MG, late-onset MG, and MG associated with the presence of a thymoma. Most MG patients can be treated effectively, but there is still a need for more specific immunological approaches.
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Affiliation(s)
- John C Keesey
- Department of Neurology, UCLA School of Medicine, Los Angeles, California, USA.
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