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1.
Neuromuscul Disord ; 38: 51-57, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38626662

RESUMEN

Azathioprine is recommended as the first-line steroid-sparing immunosuppressive agent for myasthenia gravis. Mycophenolate and methotrexate are often considered as second-line choices despite widespread consensus on their efficacy. We aimed to gather real-world data comparing the tolerability and reasons for discontinuation for these agents, by performing a national United Kingdom survey of side effects and reasons for discontinuation of immunosuppressants in myasthenia gravis. Of 235 patients, 166 had taken azathioprine, 102 mycophenolate, and 40 methotrexate. The most common side effects for each agent were liver dysfunction for azathioprine (23 %), diarrhoea for mycophenolate (14 %), and fatigue for methotrexate (18 %). Women were generally more likely to experience side effects of immunosuppressants. Azathioprine was significantly more likely to be discontinued than mycophenolate and methotrexate due to side effects. There was no significant difference in treatment cessation due to lack of efficacy. This study highlights the significant side-effect burden of treatment for myasthenia gravis. Mechanisms to reduce azathioprine toxicity should be utilised, however mycophenolate and methotrexate appear to be good treatment choices if teratogenicity is not a concern. Women are disadvantaged due to higher frequency of side effects and considerations around pregnancy and breastfeeding. Treatments with improved tolerability are needed.


Asunto(s)
Azatioprina , Inmunosupresores , Metotrexato , Miastenia Gravis , Ácido Micofenólico , Humanos , Miastenia Gravis/tratamiento farmacológico , Metotrexato/uso terapéutico , Metotrexato/efectos adversos , Femenino , Ácido Micofenólico/efectos adversos , Ácido Micofenólico/uso terapéutico , Azatioprina/efectos adversos , Azatioprina/uso terapéutico , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Adulto , Anciano , Reino Unido
2.
J Ultrasound ; 26(4): 793-797, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37540347

RESUMEN

INTRODUCTION: Open surgical muscle biopsy has traditionally been required for the histological diagnosis of myopathy but requires neurosurgical expertise with a variable diagnostic yield. Ultrasound guided percutaneous approaches are less resource intensive and invasive. This follow-up study aims to assess the diagnostic yield and tolerability of this approach to assess its utility as an adjunct to the traditional open surgical technique. METHODOLOGY: Between March of 2020 and June of 2021, 24 patients underwent a muscle biopsy following discussion at our regional neuromuscular multi-disciplinary team meeting. A consultant musculoskeletal radiologist used a modified Bergstrom needle to obtain a minimum of 2 samples under 500 mmHg of suction and ultrasound guidance. These were followed up to assess the diagnostic yield. A survey was also sent to the patients to assess the tolerability of the procedure. RESULTS: 21 out of the 24 biopsies performed provided diagnostic information. Of these 3 non diagnostic samples were obtained, two were insufficient in size and one consisted of fatty tissue. Of the 21 patients who responded to the survey, 18 rated the procedure as good or excellent with 3 patients rated it as average or poor citing administrative or communication issues rather than procedural. All 5 patients who had previously undergone surgical biopsy expressed a preference for the ultrasound guided percutaneous approach. No patients experienced any complications. CONCLUSION: This follow-up study reinforces the conclusion of its predecessor by highlighting that ultrasound guided percutaneous muscle biopsy is a useful and tolerable adjunct to the traditional surgical technique in investigating muscle disorders.


Asunto(s)
Enfermedades Musculares , Humanos , Estudios de Seguimiento , Enfermedades Musculares/diagnóstico por imagen , Biopsia con Aguja Fina , Músculos , Biopsia Guiada por Imagen/efectos adversos , Ultrasonografía Intervencional/efectos adversos , Estudios Retrospectivos
3.
BMJ Case Rep ; 14(3)2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33674300

RESUMEN

Axial myopathies with paraspinal predominance usually present with dropped head, abnormal posture or rigidity of the spine. Management of axial myopathy can be difficult and there is little data in the literature about surgical treatment. We discuss a case of axial myopathy with late-onset scoliosis and dropped head, focusing on the surgical management of the case.


Asunto(s)
Enfermedades Musculares , Escoliosis , Cabeza , Humanos , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/cirugía , Procedimientos Neuroquirúrgicos , Escoliosis/diagnóstico por imagen , Escoliosis/cirugía , Columna Vertebral
5.
Skeletal Radiol ; 49(11): 1855-1859, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32519182

RESUMEN

OBJECTIVE: We propose the use of ultrasound-guided muscle biopsy as a viable method of obtaining muscle specimen to aid the diagnosis of myopathy. We retrospectively review the diagnostic accuracy and patient feedback of ultrasound-guided muscle biopsies in our neuromuscular service. METHOD: Multidisciplinary team meeting reviewed select patients and agreed on those suitable for ultrasound-guided muscle biopsy. They then underwent biopsy using direct ultrasound guidance and a modified Bergström needle. The specimens were sent for histopathological analysis, and patients were given a feedback form. RESULTS: Ten patients underwent 11 ultrasound-guided muscle biopsies. Of these 11, one was processed incorrectly, but all others were good quality specimens suitable for analysis. All 10 of those processed correctly aided diagnosis. All patient feedback was rated good or excellent. In 4 patients with a previous unsuccessful surgical biopsy, ultrasound-guided biopsy was successful in obtaining suitable muscle. Of those 4 patients, 3 preferred ultrasound-guided biopsy, and 1 did not state a preference. DISCUSSION: Our ultrasound-guided muscle biopsy technique offers a viable alternative to surgical biopsy. It yields high-quality specimen that aids diagnosis and receives good feedback from patients. It can be performed quickly as a day case and does not require theatre space. Furthermore, direct visualization of structures minimizes the risk of complications and allows biopsy of otherwise difficult to access targets. CONCLUSION: Utilization of ultrasound guided-modified Bergström needle technique for muscle biopsy provides comparable success rates to other techniques and has practical, clinical, operational, and patient-centred benefits compared with alternative techniques.


Asunto(s)
Biopsia Guiada por Imagen , Enfermedades Musculares , Ultrasonografía Intervencional , Humanos , Músculos , Enfermedades Musculares/diagnóstico por imagen , Estudios Retrospectivos
6.
Ann N Y Acad Sci ; 1413(1): 143-153, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29377162

RESUMEN

Antibodies to the acetylcholine receptor (AChR) have been recognized for over 40 years and have been important in the diagnosis of myasthenia gravis (MG), and its recognition in patients of different ages and thymic pathologies. The 10-20% of patients who do not have AChR antibodies are now known to comprise different subgroups, the most commonly reported of which is patients with antibodies to muscle-specific kinase (MuSK). The use of cell-based assays has extended the repertoire of antibody tests to clustered AChRs, low-density lipoprotein receptor-related protein 4, and agrin. Autoantibodies against intracellular targets, namely cortactin, titin, and ryanodine receptor (the latter two being associated with the presence of thymoma), may also be helpful as biomarkers in some patients. IgG4 MuSK antibodies are clearly pathogenic, but the coexisting IgG1, IgG2, and IgG3 antibodies, collectively, have effects that question the dominance of IgG4 as the sole pathologic factor in MuSK MG. After a brief historical review, we define the different subgroups and summarize the antibody characteristics. Experiments to demonstrate the in vitro and in vivo pathogenic roles of MuSK antibodies are discussed.


Asunto(s)
Autoanticuerpos/inmunología , Miastenia Gravis/inmunología , Proteínas Tirosina Quinasas Receptoras/inmunología , Receptores Colinérgicos/inmunología , Agrina/inmunología , Humanos , Inmunoglobulina G/inmunología , Canal de Potasio Kv1.4/inmunología , Proteínas Relacionadas con Receptor de LDL/inmunología , Miastenia Gravis/clasificación
8.
Arch Neurol ; 69(8): 994-1001, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22689047

RESUMEN

BACKGROUND: Clustered acetylcholine receptor antibodies (clustered AChR-Abs) have been detected in a proportion of patients with previously "seronegative" (SN) generalized myasthenia gravis (GMG), but their presence in patients with ocular MG (OMG) and their pathogenicity in vivo are unknown. OBJECTIVE: To test the presence of clustered AChR-Abs and their pathophysiologic properties in patients with SNMG. DESIGN: Screening and diagnostic tests. SETTING: Regional specialist myasthenia center and clinical laboratory. PATIENTS: Serum samples from 16 patients with SN and OMG were tested for binding to clustered AChRs. Results from 28 further SN patients (14 OMG) were correlated with their single fiber electromyography values. MAIN OUTCOME MEASURES: Presence, complement-fixation capacity, correlation with neurophysiologic changes, and in vivo pathogenicity of clustered AChR-Abs. RESULTS: Up to 50% of patients with previous SN-OMG had complement-fixing IgG1 clustered AChR-Abs. IgG binding (n = 28) and complement deposition (n = 21) each correlated with the mean consecutive difference (jitter) on single-fiber electromyography. Injection of purified IgG from 2 patients with clustered AChR-Abs into wild-type or complement regulator-deficient mice reduced miniature end plate potential amplitudes to an extent similar to that found with AChR-Abs, and complement was deposited at the end plates. A trend was noted toward an increase in the number of packets of acetylcholine released (quantal content). CONCLUSIONS: A proportion of patients with SN-GMG or OMG have clustered AChR-Abs that correlate with their electrophysiologic features. Clustered AChR-Abs can passively transfer disease to mice, demonstrating their pathogenicity, and the mechanisms seem similar to those of patients with typical AChR-Abs.


Asunto(s)
Autoanticuerpos/sangre , Miastenia Gravis/sangre , Miastenia Gravis/diagnóstico , Receptores Colinérgicos/sangre , Adulto , Animales , Autoanticuerpos/biosíntesis , Femenino , Células HEK293 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Miastenia Gravis/fisiopatología , Trastornos de la Motilidad Ocular/sangre , Trastornos de la Motilidad Ocular/diagnóstico , Trastornos de la Motilidad Ocular/fisiopatología , Unión Proteica/fisiología , Receptores Colinérgicos/fisiología
10.
Brain ; 131(Pt 7): 1940-52, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18515870

RESUMEN

Only around 80% of patients with generalized myasthenia gravis (MG) have serum antibodies to acetylcholine receptor [AChR; acetylcholine receptor antibody positive myasthenia gravis (AChR-MG)] by the radioimmunoprecipitation assay used worldwide. Antibodies to muscle specific kinase [MuSK; MuSK antibody positive myasthenia gravis (MuSK-MG)] make up a variable proportion of the remaining 20%. The patients with neither AChR nor MuSK antibodies are often called seronegative (seronegative MG, SNMG). There is accumulating evidence that SNMG patients are similar to AChR-MG in clinical features and thymic pathology. We hypothesized that SNMG patients have low-affinity antibodies to AChR that cannot be detected in solution phase assays, but would be detected by binding to the AChRs on the cell membrane, particularly if they were clustered at the high density that is found at the neuromuscular junction. We expressed recombinant AChR subunits with the clustering protein, rapsyn, in human embryonic kidney cells and tested for binding of antibodies by immunofluorescence. To identify AChRs, we tagged either AChR or rapsyn with enhanced green fluorescence protein, and visualized human antibodies with Alexa Fluor-labelled secondary or tertiary antibodies, or by fluorescence-activated cell sorter (FACS). We correlated the results with the thymic pathology where available. We detected AChR antibodies to rapsyn-clustered AChR in 66% (25/38) of sera previously negative for binding to AChR in solution and confirmed the results with FACS. The antibodies were mainly IgG1 subclass and showed ability to activate complement. In addition, there was a correlation between serum binding to clustered AChR and complement deposition on myoid cells in patients' thymus tissue. A similar approach was used to demonstrate that MuSK antibodies, although mainly IgG4, were partially IgG1 subclass and capable of activating complement when bound to MuSK on the cell surface. These observations throw new light on different forms of MG paving the way for improved diagnosis and management, and the approaches used have applicability to other antibody-mediated conditions.


Asunto(s)
Autoanticuerpos/sangre , Inmunoglobulina G/sangre , Miastenia Gravis/inmunología , Receptores Colinérgicos/inmunología , Adulto , Reacciones Antígeno-Anticuerpo/inmunología , Autoanticuerpos/metabolismo , Sitios de Unión de Anticuerpos/inmunología , Línea Celular , Activación de Complemento/inmunología , Reacciones Falso Negativas , Feto/inmunología , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina G/metabolismo , Inmunoglobulina M/metabolismo , Microscopía Fluorescente/métodos , Miastenia Gravis/patología , Proteínas Tirosina Quinasas Receptoras/inmunología , Timo/inmunología , Timo/patología
11.
Ann N Y Acad Sci ; 1132: 84-92, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18567857

RESUMEN

Antibodies to muscle-specific kinase (MuSK) are found in a variable proportion of patients with myasthenia without typical acetylcholine receptor (AChR) antibodies, but their characteristics and pathogenic mechanisms are not fully understood. We discuss the incidence and pathogenicity of MuSK antibodies and how clinical studies, animal models, and cultured cell lines can be used to elucidate their pathogenic mechanisms. Patients without either AChR or MuSK antibodies (seronegative myasthenia) appear to present another disease subtype that is highly similar to that of typical myasthenia gravis. We demonstrate a new method that detects AChR antibodies in these patients and show that these low-affinity AChR antibodies are predominantly IgG1 and can activate complement C3b deposition. Similarly MuSK antibodies, although mainly IgG4, are partially IgG1 and can activate C3b deposition. Overall, these results suggest that complement-activation may be an important pathogenic mechanism even in patients without conventional AChR antibodies.


Asunto(s)
Anticuerpos/inmunología , Miastenia Gravis/inmunología , Miastenia Gravis/metabolismo , Receptores Colinérgicos/inmunología , Receptores Colinérgicos/metabolismo , Animales , Anticuerpos/sangre , Electrofisiología , Humanos , Miastenia Gravis/epidemiología , Miastenia Gravis/patología , Proteínas Tirosina Quinasas Receptoras/metabolismo
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