Biomedical subjects
Publications and source records attributed to A Evoli.
The authors measured anti-muscle-specific tyrosine kinase (anti-MuSK) antibodies (Abs) in 83 serum samples from 40 patients and evaluated their correlation with myasthenia gravis severity and treatment response. Ab concentrations were often reduced by immunosuppression but not after thymectomy. Both in individual cases and in the whole population, a correlation between Ab levels and disease severity was found.
The aim of this study was to compare the neurophysiological and clinical pictures of a large sample of seronegative myasthenia gravis (SNMG) patients with and without anti-MuSK antibodies. Fifty-two consecutive SNMG patients were retrospectively evaluated. They had undergone an extended neurophysiological evaluation: repetitive nerve stimulation (RNS), single fiber EMG (SFEMG), and electromyography (EMG) with nerve conduction study. A muscle biopsy was performed in 11 of 52 patients, the edrophonium test in 44 of 52 patients and anti-AChR antibodies and anti-MuSK antibodies were tested in all patients. Anti-MuSK antibodies were detected in 25 SNMG patients (48.1%). The number of women in the MuSK+ group was significantly higher (P = 0.01) than in the MuSK- group. Seronegative MuSK+ patients are more severely affected and the deficit often involves the bulbar and the respiratory muscles. No statistically significant differences were observed in the edrophonium test between MuSK+ and MuSK- groups. The RNS test was abnormal in a significantly higher number of MUSK- patients than MUSK+ patients (P < 0.00001). With regard to SFEMG data, MuSK- patients were characterized to have more severe neurophysiological pattern. Our observations showed several differences between the clinical and neurophysiological pictures of MUSK+ and MUSK- patients.
Important progress has been made in our understanding of the cellular and molecular processes underlying the autoimmune neuromuscular transmission (NMT) disorders; myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS) and neuromyotonia (peripheral nerve hyperexcitability; Isaacs syndrome). To prepare consensus guidelines for the treatment of the autoimmune NMT disorders. References retrieved from MEDLINE, EMBASE and the Cochrane Library were considered and statements prepared and agreed on by disease experts and a patient representative. The proposed practical treatment guidelines are agreed upon by the Task Force: (i) Anticholinesterase drugs should be the first drug to be given in the management of MG (good practice point). (ii) Plasma exchange is recommended as a short-term treatment in MG, especially in severe cases to induce remission and in preparation for surgery (level B recommendation). (iii) Intravenous immunoglobulin (IvIg) and plasma exchange are equally effective for the treatment of MG exacerbations (level A Recommendation). (iv) For patients with non-thymomatous autoimmune MG, thymectomy (TE) is recommended as an option to increase the probability of remission or improvement (level B recommendation). (v) Once thymoma is diagnosed TE is indicated irrespective of the severity of MG (level A recommendation). (vi) Oral corticosteroids is a first choice drug when immunosuppressive drugs are necessary in MG (good practice point). (vii) In patients where long-term immunosuppression is necessary, azathioprine is recommended together with steroids to allow tapering the steroids to the lowest possible dose whilst maintaining azathioprine (level A recommendation). (viii) 3,4-diaminopyridine is recommended as symptomatic treatment and IvIg has a positive short-term effect in LEMS (good practice point). (ix) All neuromyotonia patients should be treated symptomatically with an anti-epileptic drug that reduces peripheral nerve hyperexcitability (good practice point). (x) Definitive management of paraneoplastic neuromyotonia and LEMS is treatment of the underlying tumour (good practice point). (xi) For immunosuppressive treatment of LEMS and NMT it is reasonable to adopt treatment procedures by analogy with MG (good practice point).
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Morphologic findings of thymuses from 32 anti-acetylcholine receptor (AChR)-negative myasthenia gravis patients, 12 with and 20 without antibodies against the muscle-specific kinase (MuSK), were compared with those from 30 AChR-positive subjects. In contrast with the high frequency of thymic hyperplastic changes in AChR-positive patients, in MuSK-positive subjects histologic alterations were minimal, arguing against an intrathymic disease pathogenesis. Since hyperplastic changes were seen in 35% of MuSK-negative patients, the thymus could be involved in some of these cases.
The objective was to develop regional domains from the Myasthenia Gravis Questionnaire (MGQ) to better assess generalised, bulbar and ocular involvement in patients with myasthenia gravis (MG) and to evaluate their responsiveness. Some items from the MGQ were aggregated into 3 domains: bulbar, generalised and ocular. The study was carried out at the Institute of Neurology, EMG Service, Universita Cattolica, Rome, and the Department of Neurology, University Hospital, Modena, Italy. Ninety-three MG patients were prospectively enrolled in two neurological departments; furthermore, outcome after treatment was studied in 23 patients to evaluate responsiveness. Disease severity was scored according to a modified version of the Osserman classification and MGQ. The questionnaire appeared more sensitive than clinical examination and history to assess bulbar and ocular involvement. For example, according to the bulbar domain, 67 patients experienced bulbar symptoms whereas on clinical examination 51 of 67 were completely normal in the bulbar region. The MGQ domains appeared reliable and sensitive. Results of global MG score (GMG) and of domains appeared reliable. Domains were able to better assess the functional involvement of anatomical regions than main GMG, clinical examination and history.
Autoimmune neurological disorders are very common. Health-related quality-of-life measures, obtained through a patient-oriented tool (a self-administered questionnaire), are now considered essential in the evaluation of therapies, especially for pathologies that may affect patients' general status. We reviewed the most common autoimmune neurological disorders and their treatment, and we report on our experience on intravenous immunoglobulin (IVIG) administration and the relationship between IVIG and health-related quality of life. Generally, IVIG administration is effective in the most common autoimmune neurological diseases. Concerning the relationship between IVIG treatment and health-related quality of life, our results reveal an improvement of physical aspects of patients' health-related quality of life after IVIG administration. Conversely, the comparison of mental scores between the evaluation at baseline and the evaluation at follow-up exhibited no difference. Although the use of IVIG is effective for autoimmune neurological disorders, there are no commonly accepted protocols for the use of IVIG treatment. Further controlled studies on IVIG, including quality-of-life assessments, are necessary to develop needed evidence on the use of IVIG in clinical practice.
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OBJECTIVE: To examine the characteristics of thymoma when associated with MG and to evaluate those conditions that can complicate management and affect survival. METHODS: The study includes 207 myasthenic patients who were operated on for thymoma, with at least 1-year follow-up from surgery. MG severity and response to treatment, the occurrence of paraneoplastic diseases and extrathymic malignancies, thymoma histologic types and stages, adjuvant therapy, tumor recurrences, and causes of death were recorded. RESULTS: MG-associated thymoma was predominantly of B type and was invasive in the majority of patients. MG was generally severe, and most patients remained dependent on immunosuppressive therapy. Other paraneoplastic disorders and extrathymic malignancies were found in 9.66 and 11.11% of patients. Thymoma recurrences occurred in 18 of 115 patients with invasive tumors (15.65%) and were often associated with the onset/aggravation of autoimmune diseases. On completion of the study, MG and thymoma accounted for a similar mortality rate. CONCLUSIONS: Thymoma should be considered as a potentially malignant tumor requiring prolonged follow-up. The presence of myasthenic weakness can still complicate its management. Thymoma-related deaths are bound to outnumber those due to MG in the future.
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We describe the development and validation of an outcome measure for patients with myasthenia gravis (MG) and show the correlation of the items with conventional MG measurements. In stage I, item generation, a group of methodologists, clinical experts generated a list of 56 items. The list was based on (1) a previous study on an MG sample, (2) clinical experience and (3) items proposed by MG patients. In stage 2, reduction of items, the list was reduced on the basis of results from field testing (41 patients completed the 56-item questionnaire). In stage 3, reliability and validity were assessed. A 25-item MG questionnaire (MGQ) was generated. Results were related to conventional measures of MG severity. Furthermore, the MGQ appeared reliable, sensitive and reproducible. The questionnaire was validated as an outcome measure.
PURPOSE: To achieve a better understanding of the role of CT and MR imaging in the study of the mediastinum in patients with myasthenia gravis (MG). MATERIAL AND METHODS: Mediastinal CT and MR findings were correlated with the histopathological results in 104 thymectomized MG patients. RESULTS: CT was performed in 104 patients; in 11 of them, MR was also carried out. 44 patients had hyperplasia at histology. On CT, thymic hyperplasia was confirmed in 16 cases, thymoma was diagnosed in 10 and a normal thymus in 18 (sensitivity 36%, specificity 95%). Of 52 patients with thymoma at histology, CT showed thymoma in 46, hyperplasia in 1, and normal thymus in 5. CT showed 88.5% sensitivity and 77% specificity for thymoma. In 10 patients with invasive thymoma, CT was indiscriminate, while invasiveness was detected in 7 cases at MR (70% sensitivity) and at CT in 1 case. Both CT and MR detected tumor recurrence in 5 cases, but the exact localization and degree of invasion were best defined by MR. CONCLUSION: In MG patients CT is a sensitive, specific and efficient modality for detecting thymoma, but is less so for detecting thymic hyperplasia. MR was shown to be accurate in detecting invasive thymoma both preoperatively and in postoperative follow-up.
We assessed the health-related quality of life (HRQoL) of patients with myasthenia gravis (MG) and correlated it with the physician's measurements of MG. Patients with MG were evaluated by means of (1) self-administered questionnaires, (2) clinical examination, (3) Osserman classification, (4) anti-AChR antibody, and (5) neurophysiology. Relationships between patient-oriented assessment and conventional clinical-neurophysiological and serological findings were evaluated. A total of 46 patients, inpatients and outpatients (mean age 50.7 years, range 11-77 years, 17 males, 29 females) with MG diagnosis were studied. The Osserman scale and clinical examination findings were significantly related to the physical aspects of HRQoL. Mental aspects of the quality of life were not progressively involved as muscle deficit progressed, but even in a mild clinical picture, the mental aspects were deteriorated. Patient-oriented measures proved that the patient's quality of life was impaired especially with regard to physical aspects. Our data demonstrated that clinical measurements are related to the HRQoL. The results may be useful in developing a disease-specific patient-oriented tool.
Myasthenia gravis (MG) induces a reduction of transient evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs) that reverses partially after administration of an acetylcholinesterase (AChE) inhibitor. In normal subjects a contralateral acoustic stimulation (CAS) produces an amplitude reduction of TEOAEs and DPOAEs. This effect, called contralateral suppression (CS), is mediated by the efferent auditory system. Twenty subjects affected by MG underwent DPOAE recording with and without contralateral white noise in a drug-free baseline period ('basal') and 1 h ('post') after administration of a reversible AChE inhibitor. In 'basal' condition CAS did not induce significant DPOAE amplitude changes but a paradoxical slight increase was observed. After drug administration, CAS produced a significant decrease of DPOAE amplitudes for middle frequencies (f(2) between 1306 and 2600 Hz). In normal controls CAS caused a significant decrease (P<0.001) for all frequencies. The amount of CS in controls and in the MG 'post' condition was not significantly different. The increased acetylcholine (ACh) availability following drug consumption seems to partially restore outer hair cell function and enhances their electromotility; a further influx of ACh due to CAS yields to restoration of the CS. These findings also suggest that DPOAEs may be useful in the diagnosis of MG and for monitoring the effectiveness of treatment.
The term ocular myasthenia gravis refers to the disease clinically restricted to extrinsic ocular muscles. It can be disabling as ptosis, and to a greater extent diplopia, both interfere with daily activities. Although ocular disturbances are the most frequent initial complaints in myasthenic patients, symptoms usually progress to generalized disease and only 15% of patients complain of purely ocular weakness for the entire course of their illness. Secondary generalization occurs with the highest frequency in the first 2 years from the onset. Both the severity of symptoms and the risk of generalization should be taken into account when devising a therapeutic plan for these patients. Anticholinesterases are of limited efficacy and a considerable proportion of patients require additional therapy. Corticosteroid therapy, generally prednisone on an alternate-day schedule, is very effective, but a reason for concern is represented by the frequent need for long-term administration with increased risk of severe complications. In patients unresponsive to prednisone or requiring too high dosages, immunosuppressive drugs like azathioprine should be used with the same criteria applied in generalized myasthenia. As corticosteroids and immunosuppressants reduce the chance of generalization, their use is justified in patients with recent-onset disabling disease. In long-standing cases with low risk of generalization, treatment is aimed at the relief of symptoms and pharmacological therapy should be reduced to the minimum effective dosage. The indication for thymectomy in ocular myasthenia remains highly controversial and should be reserved for disabled patients in the early stages of the disease.
Outer hair cells (OHCs) are the source of otoacoustic emissions, following a tropomyosin-miosin-dependent contraction, which are regulated by the olivocochlear bundle via the release of acetylcholine (ACh). ACh acts on ACh receptors (AChR) located on the OHC post-synaptic membrane. In myasthenia gravis (M.G.) neuromuscular transmission is reduced due to the action of AChR autoantibodies. It has previously been shown that M.G. induces a reduction in transient evoked otoacoustic emissions (TEOAEs), which is reversed after administration of a cholinesterase (AChE) inhibitor. Distortion product otoacoustic emissions (DPOAEs) were recorded before and 60 min after oral administration of 60 mg pyridostigmine bromide in 25 patients with normal hearing affected by M.G. The results were compared with those from 25 age-matched normal controls. Mean values of DPOAE amplitude in myasthenic patients were significantly (p < 0.05) lower at all frequencies before drug administration. All patients showed an overall significant (p < 0.05) increase in DPOAE amplitude after drug administration, although without reaching the control values. Such a recovery was more evident and highly significant (p < 0.01) for middle and high frequencies and could be explained by a higher concentration of ACh receptors in the basal and middle cochlear turns. These data seem to confirm the role of ACh in the neurotransmission of the auditory efferent system and may represent a new in vivo model for the investigation of the physiology of this system.
BACKGROUND AND OBJECTIVE: In typical cases, the patient's history and clinical examination make it possible to diagnose ocular myasthenia gravis (OMG). But, in many cases a clear clinical picture is not present and OMG diagnosis is very difficult because gold diagnostic standard tests are not available. The diagnostic tests for OMG are usually unable to display a good sensitivity and specificity simultaneously. In this paper, we studied 86 cases submitted for suspected OMG. METHODS: The patients were studied clinically and with various other tests used in OMG diagnosis (SFEMG, repetitive nerve stimulation, Ab anti AChR titration, tensilon test). RESULTS AND CONCLUSION: SFEMG showed the highest sensitivity (100%) while Ab anti AChR showed the highest specificity (100%). To our knowledge this is the largest population of suspected OMG studied using most of the diagnostic parameters, reported in the literature.