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Background

This is a recently described disease with the characteristic findings of large ulcerative nodules on the dorsum of the hands. Under the microscope, the characteristic findings of a leukocytoclastic vasculitis are usually present.

OUTLINE

Epidemiology  
Disease Associations  
Pathogenesis  
Laboratory/Radiologic/
Other Diagnostic Testing
 
Gross Appearance
and Clinical Variants
 
Histopathological Features
and Variants
 
Special Stains/
Immunohistochemistry/
Electron Microscopy
 
Differential Diagnosis  
Prognosis  
Treatment Thymoma
-------------------
Intravenous Immunoglobulin
Thymectomy
Commonly Used Terms  
Internet Links  

EPIDEMIOLOGY CHARACTERIZATION
GEOGRAPHY  
AMSTERDAM  


The natural course of myasthenia gravis: a long term follow up study.

Oosterhuis HJ.

Department of Neurology, State University Groningen, The Netherlands.

J Neurol Neurosurg Psychiatry 1989 Oct;52(10):1121-7 Abstract quote

A long term follow up study is presented of 73 patients with myasthenia gravis, living in Amsterdam between 1926 and 1965. In the period 1961-65 the annual incidence was 3.1, the prevalence 53 per million.

Maximum severity of the disease occurred during the first seven years after onset in 87%. Eighteen (29%) patients died, of whom eight had a thymoma (TH). Spontaneous improvement or remission occurred at any time during the follow up. At the end of the study (1985) 16 (22%) patients were in a complete clinical remission, 13 (18%) had improved considerably (3 with prednisone), 12 (16%) had improved moderately, 12 (16%) had remained unchanged and two had deteriorated. If the early deaths are excluded the outcome is similar in the early and the late onset group without TH. Patients with TH had a less favourable course.

Associated autoimmune diseases were diagnosed in 25% (n = 58). Because most of these patients were treated with anticholinesterases only, the evolution of their clinical state represents the natural course of MG.

ENGLAND  


Myasthenia gravis: a population based epidemiological study in Cambridgeshire, England.

Robertson NP, Deans J, Compston DA.

University of Cambridge Neurology Unit, Addenbrooke's Hospital, UK.

J Neurol Neurosurg Psychiatry 1998 Oct;65(4):492-6 Abstract quote

OBJECTIVES: To perform a comprehensive survey of myasthenia gravis in the county of Cambridgeshire, England, establishing contemporary epidemiological data.

METHODS: Cases were ascertained from multiple sources. Prevalent patients were visited and assessed by means of a standardised questionnaire and examination complemented by review of medical case notes.

RESULTS: One hundred cases were identified in a population of 684000 (prevalence 15 per 100000 population, 95% confidence intervals (95% CIs) 12-18). Thirty eight new diagnoses were made over a five year period providing an incidence of 1.1/100000 population/year. The sex ratio was 2:1 F:M. After a mean follow up of 11.7 years, symptomatic disease was still restricted to ocular muscles in 25 patients. Thirty four of 100 patients underwent thymectomy a mean of 0.8 years after presentation, and a thymoma was present in 12. Highest remission rates were seen in patients presenting with generalised disease who underwent thymectomy but did not have a thymoma (27%). Cosegregation of an additional autoimmune disease occurred in 27 patients and in 24/49 (49%) women with onset<50 years of age.

CONCLUSIONS: This, the second highest reported prevalence for myasthenia, is likely to be the result of optimum case ascertainment, increased disease duration, application of complex diagnostic tests, and the impact of an aging population leading to a relative increase in the prevalence of ocular myasthenia.

SWEEDEN  


Epidemiology of myasthenia gravis: a population-based study in Stockholm, Sweden.

Kalb B, Matell G, Pirskanen R, Lambe M.

Neurological Division, Nacka Narsjukhus, Karolinska Institutet, Stockholm, Sweden.

Neuroepidemiology 2002 Sep-Oct;21(5):221-5 Abstract quote

A regional database of myasthenia gravis (MG) patients was used to estimate the prevalence and selected characteristics of the disease in the county of Stockholm, Sweden.

The prevalence of MG was 14.1/100,000 (17.1 for women and 10.8 for men). The mean age at onset for women and men was 34.9 and 48.5 years, respectively. About 60% of patients were diagnosed within the first year after initial symptoms. Generalized MG was found in 79% of patients, and 10% had severe symptoms. Almost two thirds of the patients had undergone thymectomy, and 30% needed immunosuppressive treatment.

The increase in the prevalence of MG since the 1960s probably reflects an improvement in prognosis and higher detection rates of patients with milder symptoms. A delay in diagnosis indicates that early signs and symptoms of MG are still not well known by all doctors.

 

DISEASE ASSOCIATIONS CHARACTERIZATION
AUTOIMMUNE DISEASE  

Myasthenia gravis and associated autoimmune diseases in children.

Tsao CY, Mendell JR, Lo WD, Luquette M, Rennebohm R.

Department of Pediatrics, College of Medicine and Public Health, Ohio State University, Columbus, USA.

J Child Neurol 2000 Nov;15(11):767-9 Abstract quote

Myasthenia gravis has been associated with other autoimmune disorders.

We report two children with myasthenia gravis and another autoimmune disease: an 18-month-old boy with ocular myasthenia gravis and Hashimoto's disease and a 14-year-old girl presenting with autoimmune polymyositis, then generalized myasthenia gravis 2 years later.

The rare combinations of myasthenia gravis and Hashimoto's disease or polymyositis in children are discussed, and we also briefly review myasthenia gravis and other associated autoimmune diseases in children.

THYMOMA  

 

PATHOGENESIS CHARACTERIZATION
ANTIBODIES TO ACETYLCHOLINE RECEPTORS  


Experimental autoimmune myasthenia gravis in naive non-obese diabetic (NOD/LtJ) mice: susceptibility associated with natural IgG antibodies to the acetylcholine receptor.

Quintana FJ, Pitashny M, Cohen IR.

Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.

 

Int Immunol 2003 Jan;15(1):11-6 Abstract quote

Naive non-obese diabetic (NOD/LtJ) mice spontaneously produce natural IgG autoantibodies against self-antigens associated with the experimental autoimmune diseases to which they are susceptible: insulin-dependant diabetes mellitus, systemic lupus erythematosus and experimental autoimmune encephalomyelitis.

We discovered recently that NOD/LtJ mice also spontaneously produce IgG antibodies to the acetylcholine receptor (AchR), an antigen that can induce experimental autoimmune myasthenia gravis (EAMG) in susceptible rodents. However, there are no reports indicating that NOD/LtJ mice are susceptible to EAMG.

To test whether the presence of spontaneous IgG autoantibodies can predict susceptibility to an autoimmune disease, we challenged NOD/LtJ mice using a standard protocol to induce EAMG. We now report that NOD/LtJ mice developed EAMG, although to a somewhat lesser degree than did C57BL/6 mice, a strain regarded as highly susceptible to the disease. Both strains produced comparable levels of immune antibodies to AchR of the complement-fixing isotypes IgG2a and IgG2b; however, NOD/LtJ mice produced significantly more IgG1. An antigen-specific T cell proliferative response to AchR of the same magnitude was detected in both strains, together with the secretion of similar amounts of IFN-gamma.

Thus, NOD/LtJ mice are susceptible to EAMG and disease induction is accompanied by immune responses comparable to those seen in the susceptible strain C57BL/6. These results support the association between specific, natural IgG autoantibodies and susceptibility to the induction of a particular autoimmune disease.

DECAY ACCELERATING FACTOR  


Markedly enhanced susceptibility to experimental autoimmune myasthenia gravis in the absence of decay-accelerating factor protection.

Lin F, Kaminski HJ, Conti-Fine BM, Wang W, Richmonds C, Medof ME.

Institute of Pathology, Case Western Reserve University, University Hospitals of Cleveland, and Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio 44106, USA.

J Clin Invest 2002 Nov;110(9):1269-74 Abstract quote

Myasthenia gravis (MG) is an autoimmune neuromuscular transmission disorder characterized by loss of acetylcholine receptors (AChR's) due primarily to the production of anti-AChR autoantibodies. In this study we investigated whether the presence of decay-accelerating factor (DAF or CD55), an intrinsic complement regulator, protects against the development of disease.

Experimental autoimmune MG was induced in Daf1(-/-) mice (devoid of neuromuscular DAF protein) and their Daf1(+/+) littermates by injection of rat anti-AChR mAb McAb-3. After twenty-four hours, grip strength assessment revealed that Daf1(-/-) mice exhibited hold times of less than 30 seconds, compared with more than 8 minutes for the Daf1(+/+) controls. The weakness was reversed by edrophonium, consistent with a myasthenic disorder. Immunohistochemistry revealed greatly augmented C3b deposition localized at postsynaptic junctions, and radioimmunoassays showed more profound reductions in AChR levels.

Electron microscopy demonstrated markedly greater junctional damage in the Daf1(-/-) mice compared with the Daf1(+/+) littermates. Control studies showed equivalent levels of other cell surface regulators, i.e., Crry and CD59.

The results demonstrate that mice that lack DAF are markedly more susceptible to anti-AChR-induced MG, which simulates the primary mechanism in the human disease, and strongly suggest that in disease flares complement inhibitors might have therapeutic value.

 

LABORATORY/
RADIOLOGIC/
OTHER TESTS

CHARACTERIZATION
RADIOLOGIC  


Thymic lesions and myasthenia gravis. Diagnosis based on mediastinal imaging and pathological findings.

Pirronti T, Rinaldi P, Batocchi AP, Evoli A, Di Schino C, Marano P.

Institutes of Radiology and Neurology, Catholic University, Rome, Italy.

Acta Radiol 2002 Jul;43(4):380-4 Abstract quote

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.


Thymic lesions in patients with myasthenia gravis: characterization with thallium 201 scintigraphy.

Higuchi T, Taki J, Kinuya S, Yamada M, Kawasuji M, Matsui O, Nonomura A, Bunko H, Tonami N.

Department of Nuclear Medicine, Kanazawa University School of Medicine, Takaramachi 13-1, Kanazawa, Ishikawa, Japan.

Radiology 2001 Oct;221(1):201-6 Abstract quote

PURPOSE: To assess thallium 201 ((201)Tl) single photon emission computed tomography (SPECT) for evaluation of thymic lesions associated with myasthenia gravis (MG), including lymphoid follicular hyperplasia (LFH) and thymoma.

MATERIALS AND METHODS: (201)Tl SPECT and computed tomography (CT) were performed preoperatively in 46 patients with MG who had undergone thymectomy. SPECT was conducted 15 (early image) and 180 (delayed image) minutes after (201)Tl injection. Results were visually assessed, and (201)Tl uptake ratios (thymic lesion count density/lung count density) were measured for quantitative analysis. Uptake was analyzed among the normal thymus, LFH, and thymoma patient groups.

RESULTS: Histopathologic results indicated a normal thymus, LFH, and thymoma in 19, 16, and 11 patients, respectively. Mean uptake ratios in the normal thymus, LFH, and thymoma were 0.96 (95% CI: 0.90, 1.03), 1.14 (95% CI: 1.04, 1.25), and 1.87 (95% CI: 1.56, 2.25), respectively, on early images and 1.09 (95% CI: 1.00, 1.18), 1.65 (95% CI: 1.48, 1.85), and 2.03 (95% CI: 1.65, 2.50), respectively, on delayed images. Thymoma showed more intense (201)Tl accumulation than did the normal thymus (P <.001) and LFH (P <.001) on early images. Both thymoma (P <.001) and LFH (P <.001) displayed more intense uptake than did the normal thymus on delayed images.

CONCLUSION: (201)Tl SPECT can enable differentiation between normal thymus, LFH, and thymoma in patients with MG.

LABORATORY MARKERS  
SERUM ANTIBODIES AGAINST ACETYLCHOLINE RECEPTORS  


Antibodies to acetylcholine receptor in parous women with myasthenia: evidence for immunization by fetal antigen.

Matthews I, Sims G, Ledwidge S, Stott D, Beeson D, Willcox N, Vincent A.

Lab Invest 2002 Oct;82(10):1407-17 Abstract quote

The weakness in myasthenia gravis (MG) is mediated by autoantibodies against adult muscle acetylcholine receptors (AChR) at the neuromuscular junction; most of these antibodies also bind to fetal AChR, which is present in the thymus. In rare cases, babies of mothers with MG, or even of asymptomatic mothers, develop a severe developmental condition, arthrogryposis multiplex congenita, caused by antibodies that inhibit the ion channel function of the fetal AChR while not affecting the adult AChR.

Here we show that these fetal AChR inhibitory antibodies are significantly more common in females sampled after pregnancy than in those who present before pregnancy, suggesting that they may be induced by the fetus. Moreover, we were able to clone high-affinity combinatorial Fab antibodies from thymic cells of two mothers with MG who had babies with arthrogryposis multiplex congenita. These Fabs were highly specific for fetal AChR and did not bind the main immunogenic region that is common to fetal and adult AChR. The Fabs show strong biases to VH3 heavy chains and to a single Vkappa1 light chain in one mother. Nevertheless, they each show extensive intraclonal diversification from a highly mutated consensus sequence, consistent with antigen-driven selection in successive steps.

Collectively, our results suggest that, in some cases of MG, initial immunization against fetal AChR is followed by diversification and expansion of B cells in the thymus; maternal autoimmunity will result if the immune response spreads to the main immunogenic region and other epitopes common to fetal and adult AChR.


Determination of anti-acetylcholine receptor antibodies in myasthenic patients by use of time-resolved fluorescence.

Ricny J, Simkova L, Vincent A.

Institute of Physiology, Academy of Sciences of Czech Republic, Videoska 1083, 142 20 Prague, Czech Republic.

Clin Chem 2002 Mar;48(3):549-54 Abstract quote

BACKGROUND: Autoantibodies against nicotinic acetylcholine receptor (nAChR) in myasthenia gravis (MG) patients are usually detected by radioimmunoprecipitation assays using extracted acetylcholine receptors labeled irreversibly with 125I-alpha-bungarotoxin (alpha-BuTx). To provide a nonradioactive immunoassay, we established an assay using nAChRs labeled with Eu(3+)-alpha-cobratoxin (alpha-CTx).

METHODS: We derivatized alpha-CTx with a diethylenetriaminepentaacetate moiety and formed a complex with Eu(3+). The complex was purified by HPLC, and the fractions were tested for binding to Torpedo and human nAChRs. The most active fractions were used to label nAChRs for the immunoprecipitation assay, and the bound Eu(3+) was quantified by time-resolved fluorescence.

RESULTS: Eu(3+)-labeled alpha-CTx competed with 125I-alpha-BuTx for binding to Torpedo nAChRs and saturated the binding sites of human nAChRs, with a K(d) of 7.2 x 10(-9) mol/L. Results of the immunoassay performed with Eu(3+)-labeled alpha-CTx were similar to those obtained with 125I-alpha-BuTx, with a slightly higher limit of detection [0.3 nmol/L (n = 6) vs approximately 0.1 nmol/L for isotopic assay]. None of 34 negative sera tested (16 healthy controls, 10 patients with nonmyasthenia-related disease, 8 patients seronegative for MG) gave a value >0.3 nmol/L. Of the 35 positive myasthenic sera (with antibody values, previously determined by isotopic assay, of 0.4-1290 nmol/L) compared in the two assays, 32 tested positive with the Eu(3+) assay. Linear regression analysis yielded the equation: y = 1.035x - 0.013 nmol/L; S(y:x) = 0.172 nmol/L; r(2) = 0.977.

CONCLUSIONS: The new time-resolved fluorescence method for quantification of antibodies to nAChRs in MG patients provides a performance similar to that of the widely used isotopic assay and could be used in laboratories with restricted use of isotopes.


Myasthenia gravis muscle antibodies examined by ELISA: IgG and IgM antibodies characterize different patient subgroups.

Hofstad H, Ulvestad E, Gilhus NE, Matre R, Aarli JA.

Broegelmann Research Laboratory for Microbiology, University of Bergen, Norway.


Acta Neurol Scand 1992 Apr;85(4):233-8 Abstract quote

Sera from 90 myasthenia gravis (MG) patients were examined for antibodies against skeletal muscle citric acid extract (CA) antigens by ELISA and indirect haemagglutination (IHA). 31% (ELISA) and 24% (IHA) of the sera were positive, and the results of the two tests were in good agreement. 18 of 28 patients positive in ELISA had IgG CA-antibodies, 10 had IgM and 3 IgA CA-antibodies.

The patients with IgG antibodies had a high mean age of MG disease onset, and 9/14 thymectomized patients had a thymoma. Patients with IgM CA-antibodies had a much lower age of onset and 4/5 thymectomized patients had thymus hyperplasia.

IgM antibody positive patients had a long disease duration, indicating that they produce IgM antibodies for an indefinite period of time without switching to IgG antibody production.

 

GROSS APPEARANCE/
CLINICAL VARIANTS
CHARACTERIZATION
GENERAL  


Difference in distribution of muscle weakness between myasthenia gravis and the Lambert-Eaton myasthenic syndrome.

Wirtz PW, Sotodeh M, Nijnuis M, Van Doorn PA, Van Engelen BG, Hintzen RQ, De Kort PL, Kuks JB, Twijnstra A, De Visser M, Visser LH, Wokke JH, Wintzen AR, Verschuuren JJ.

Department of Neurology, Leiden University Medical Centre, Leiden, Netherlands.

J Neurol Neurosurg Psychiatry 2002 Dec;73(6):766-8 Abstract quote

BACKGROUND: Myasthenia gravis and the Lambert-Eaton myasthenic syndrome (LEMS) may have a similar distribution of muscle weakness. Deciding on a diagnosis of myasthenia gravis or LEMS on clinical grounds may therefore be difficult.

OBJECTIVE: To compare the localisation of initial muscle weakness and the distribution of weakness at the time of maximum severity in patients with myasthenia gravis and LEMS.

SUBJECTS: 101 patients with myasthenia gravis and 38 patients with LEMS.

RESULTS: In myasthenia gravis, initial weakness involved extraocular muscles in 59%, bulbar muscles in 29%, and limb muscles in 12% of the patients. In LEMS no patient had ocular weakness, 5% had bulbar weakness, and 95% had weakness of the limbs as the first symptom (p < 0.001). At the point of maximum severity, weakness in myasthenia gravis was purely ocular in 25%, oculobulbar in 5%, restricted to the limbs in 2%, and present in both oculobulbar muscles and limbs in 68%. At this point, none of the LEMS patients had weakness restricted to extraocular or bulbar muscles (p = 0.002). The legs were affected in all LEMS patients, whereas in 12 patients with generalised myasthenia gravis limb weakness was restricted to the arms (p = 0.024).

CONCLUSIONS: In a patient suspected to have a myasthenic syndrome whose first symptom is ocular weakness, LEMS is virtually excluded. Limb weakness confined to the arms is only found in generalised myasthenia gravis and not in LEMS. Muscle weakness in myasthenia gravis tends to develop in a craniocaudal direction, and in the opposite direction in LEMS.

VARIANTS  
LARYNGEAL  


Laryngeal myasthenia gravis: report of 40 cases.

Mao VH, Abaza M, Spiegel JR, Mandel S, Hawkshaw M, Heuer RJ, Sataloff RT.

Department of Otolaryngology-Head and Neck Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

J Voice 2001 Mar;15(1):122-30 Abstract quote

Myasthenia gravis, an autoimmune disorder of the neuromuscular junction, is usually recognized because of ocular complaints or generalized weakness.

We report a series of 40 patients who presented with dysphonia as their initial and primary complaint. Diagnostic testing included strobovideolaryngoscopy, electromyography (EMG) with repetitive stimulation and Tensilon testing, and laboratory and radiographic evaluation. Strobovideolaryngoscopy most commonly revealed fluctuating impairment of vocal fold mobility, either unilateral or bilateral. EMG detected evidence of neuromuscular junction abnormalities in all patients. Only one patient had evidence of antiacetylcholine receptor (ACh-R) antibodies, but many other abnormalities suggestive of autoimmune dysfunction were present.

Pyridostigmine therapy was initiated in 34 patients but was not tolerated in 4. Of the remaining 30 patients, 23 reported improvement of symptoms.

We conclude that myasthenia gravis can present with symptoms confined primarily to the larynx and should be included in the differential diagnosis of dysphonia.

JUVENILE ONSET  


Outcome in juvenile-onset myasthenia gravis: a retrospective study with long-term follow-up of 79 patients.

Lindner A, Schalke B, Toyka KV.

Department of Neurology, Julius-Maximilians-University Wurzburg, Germany.

J Neurol 1997 Aug;244(8):515-20 Abstract quote

Randomised and controlled treatment studies of juvenile-onset myasthenia gravis have not been published.

We therefore report our retrospective analysis of 79 patients with juvenile-onset myasthenia gravis observed for as long as 30 years. The mean age at onset was 13.7 years and median follow-up 7.7 years.

The initial presentation was generalised disease in 90% and ocular disease in the remaining patients. Sixty-five patients (82%) were thymectomised. In 14 of these, treatment consisted of a combination of azathioprine (2-3 mg/kg), corticosteroids (prednisolone up to 60 mg for a maximum duration of 12 months with subsequent tapering) and acetylcholinesterase (AChE) inhibitors, and of azathioprine and AChE inhibitors in 27 patients. One patient received azathioprine and 22 AChE inhibitors only; in another no further medication was necessary. In the severely affected group (n = 16), plasmapheresis was performed additionally before thymectomy and continued for some time after the operation. Treatment was started between 1 and 14 months (mean 2.4 months) after the onset of myasthenic symptoms. No thymectomy was done in 14 patients, and immunosuppressive treatment and AChE inhibitors were given in 9 of these cases. One patient received azathioprine only; 4 patients received AChE inhibitors only.

The histology of the thymus gland showed follicular hyperplasia in 89% of the 65 thymectomised patients and normal findings in the remainder. Remission occurred in 60% of patients who underwent thymectomy and in 29% of those who were not thymectomised. Hyperthyroidism (6 patients, 8%), diabetes mellitus (2 patients, 3%) and rheumatoid arthritis (2 patients, 3%) were the most frequent associated immune-mediated diseases. Epileptic seizures and neoplasia were coincident diseases in 2 (3%) and 3 (4%) patients, respectively. There were no deaths from thymectomy or from immunosupression.

This open, retrospective analysis suggests that juvenile-onset myasthenia gravis can be treated satisfactorily in most patients by the use of thymectomy and/or immunosupressive medication.

LATE ONSET  


Late-onset myasthenia gravis: a changing scene.

Aarli JA.

Department of Neurology, University of Bergen, Norway

Arch Neurol 1999 Jan;56(1):25-7 Abstract quote

The prevalence of myasthenia gravis (MG) among middle-aged and older patients has increased. Patients with early-onset MG live longer than before, but there is also an increase in late-onset MG (onset of the disease after the age of 50 years in patients with no clinical or paraclinical evidence of a thymoma). Epidemiological data support using the age of 50 years to separate early- and late-onset MG.

The main immunological difference between early- and late-onset MG is the presence of antibodies to muscle titin, which are detected in approximately 50% of patients with late-onset MG.

Treatment of late-onset MG has to be tailored both to the age of the patient and to the immunological findings of that particular form of MG.

OCULAR  


Myasthenia gravis with ocular involvement in older patients.

Weizer JS, Lee AG, Coats DK.

Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Texas Children's Hospital, Houston, Tex., USA.

Can J Ophthalmol 2001 Feb;36(1):26-33 Abstract quote

BACKGROUND: There has been little previous study reporting the eye findings and presentation of elderly patients with myasthenia gravis. The purpose of this study was to review the findings and course of myasthenia gravis after the sixth decade of life.

METHODS: Retrospective observational case series. The authors reviewed the clinical records of 27 patients with onset of myasthenia gravis at age 60 years or more who were seen at a tertiary care academic ophthalmology centre in Houston between January 1992 and March 1999. The diagnosis of myasthenia gravis was based on conventional clinical and laboratory criteria.

RESULTS: Twenty patients (74%) were men. Of the 16 patients who underwent testing for anti-acetylcholine receptor antibodies, 11 (69%) were seropositive. Concurrent thyroid disease was found in seven patients (26%), including five (71%) of the seven women. No patient had thymoma. Sixteen patients (59%) manifested generalized symptoms during follow-up; 12 did so within 1 year of disease onset. Patients responded well to both anticholinesterase and corticosteroid therapy. At the most recent follow-up visit 18 patients (67%) were clinically improved, and no patient was clinically worse.

INTERPRETATION: Myasthenia gravis in this study was characterized by a male predominance, high rate of concurrent thyroid disease, high rate of progression to mild generalized symptoms, absence of thymoma, good response to medical therapy and minimal life-threatening complications. Clinicians should consider the diagnosis of myasthenia gravis in an older patient presenting with diplopia or ptosis.

TOUNGE ATROPHY  


Atrophy of the tongue with persistent articulation disorder in myasthenia gravis: report of 10 patients.

De Assis JL, Marchiori PE, Scaff M.

Department of Neurology, University of Sao Paulo Medical School, Brazil.

Auris Nasus Larynx 1994;21(4):215-8 Abstract quote

Ten patients with atrophy of the tongue, from a group of 752 with generalized acquired myasthenia gravis (MG), were studied.

Tongue atrophy developed late in the majority of patients and was accompanied by tongue paresis (70% of the cases) and eventually associated to atrophy of other muscles of the palate, especially the uvula. All the patients exhibited severe forms of MG with bulbar involvement, mainly persistent dysphonia and dysphagia, almost always refractory to treatment. There is no correlation among atrophy of the tongue, sex, and thymus pathology.

There is correlation between severeness of symptoms and early, persistent and treatment refractory dysphonia and dysphagia.

 

HISTOLOGICAL TYPES CHARACTERIZATION
GENERAL  
VARIANTS  
THYMUS  


Thymus in myasthenia gravis: comparison of CT and pathologic findings and clinical outcome after thymectomy.

Nicolaou S, Muller NL, Li DK, Oger JJ.

Department of Radiology, University of British Columbia, Vancouver, Canada.

 

Radiology 1996 Nov;201(2):471-4 Abstract quote

PURPOSE: To correlate computed tomographic (CT) appearance of the thymus with results from histologic examination of thymic tissue and clinical outcome in patients with generalized myasthenia gravis who underwent thymectomy.

MATERIALS AND METHODS: Forty-five patients with myasthenia gravis underwent CT of the thorax and thymectomy. Findings at clinical follow-up were available in all patients.

RESULTS: Twenty-six patients had normal CT findings, seven had a diffusely enlarged thymus, and 12 had a focal mass. The results of histologic examination showed that 16 of 26 patients with normal CT findings had normal thymic tissue and 10 had lymphoid follicular hyperplasia; all seven patients with an enlarged thymus had lymphoid hyperplasia. Five of 12 patients with a focal mass at CT had lymphoid hyperplasia, and seven had thymoma. Clinical improvement following thymectomy was observed in 27 (93%) of 29 patients with lymphoid hyperplasia or thymoma and 11 (69%) of 16 patients with normal histologic examination (P < .03, chi(2) test).

CONCLUSION: The presence of an enlarged thymus or a focal mass in patients with myasthenia gravis indicates lymphoid hyperplasia or thymoma. However, CT is of limited value in distinguishing lymphoid follicular hyperplasia from a normal thymus or thymoma and in predicting clinical outcome.

 

PROGNOSIS AND TREATMENT CHARACTERIZATION
PROGNOSTIC FACTORS  
GENERAL  


Prognosis of myasthenia gravis: a retrospective study of 380 patients.

Cosi V, Romani A, Lombardi M, Raiola E, Bergamaschi R, Piccolo G, Citterio A, Berzuini C.

Istituto Neurologico C. Mondino, Pavia, Italy.

J Neurol 1997 Sep;244(9):548-55 Abstract quote

The 9139 follow-up records of 438 myasthenia gravis (MG) patients were reviewed. Excluding those patients who were diagnosed 5 or more years after symptom onset (n = 37) and those who experienced only oculomotor symptoms throughout follow-up (n = 21), there were 380 patients.

A survival analysis approach was used to assess the influence of prognostic factors on the following endpoints: (a) stable complete remission, (b) complete remission of at least 6 months and (c) pharmacological remission of at least 6 months. Early diagnosis was associated with a better prognosis with respect to all endpoints.

Thymectomy also improved the prognosis but only for those patients without thymoma. Later MG onset was associated with a higher tendency to achieve pharmacological remission.


Myasthenia gravis: diagnosis and follow-up of 100 consecutive patients.

Beekman R, Kuks JB, Oosterhuis HJ.

Department of Neurology, University Hospital, Groningen, The Netherlands.

J Neurol 1997 Feb;244(2):112-8 Abstract quote

One hundred consecutive patients with myasthenia gravis (MG) referred between 1985 and 1989 were analysed for epidemiological characteristics, evolution of early signs, delay in diagnosis, yield of diagnostic tests and effects of treatment.

The female to male ratio was 1.6:1.0. Sixteen patients had a thymoma. Ocular MG occurred in 14. Associated autoimmune diseases were found in 15 patients. In 34% of the women and 10% of the men the diagnosis was delayed for more than 2 years. In the first 3 months progression was more rapid in men than in women. Anti-acetylcholine receptor antibodies were found in 94% of the patients with generalized MG and in 29% of the ocular patients. The neostigmine or the edrophonium test was positive in 84% of the generalized and in 60% of the ocular patients. Electromyography was diagnostic in 71% of the generalized and in 42% of the ocular patients tested. Thymectomy was performed in 56 patients (12 with thymomas). Fifty-one per cent were treated with one or more immunosuppressive drugs, at any time.

After a mean follow-up of 9.6 years after onset remissions had occurred in 43%, considerable improvement in 25%, moderate improvement in 20% and 12% remained unchanged. There were no deaths due to MG. Thirty-six per cent remained dependent on immunosuppressive drugs. Medication-free remission was most frequent (35%) in the early-onset (< 50 years) group. Side-effects of pyridostigmine were noted in 34% of 99 patients, of prednisone in 65% of 49 patients, and of azathioprine in 54% of 28 patients, but these necessitated stopping the drug in only 1%, 10% and 14% respectively.


A multicentre follow-up study of 1152 patients with myasthenia gravis in Italy.

Mantegazza R, Beghi E, Pareyson D, Antozzi C, Peluchetti D, Sghirlanzoni A, Cosi V, Lombardi M, Piccolo G, Tonali P, et al.

Neurological Institute C. Besta, Milan, Italy.

J Neurol 1990 Oct;237(6):339-44 Abstract quote

A multicentre retrospective study was carried out on the characteristics and course of myasthenia gravis (MG) in Italy. Data from 1152 patients, fairly representative of the myasthenic population seeking medical advice, were analysed for diagnostic criteria, clinical aspects and therapeutic approaches. Mean follow-up was 4.9 years. The disease was correctly diagnosed within 2 years of the onset in 80% of cases.

Onset of symptoms peaked in the second and third decade in females and fell between 20 and 59 years in males. At first observation 87% of the patients had generalized MG. Maximal worsening was observed within 3 years in 77% of patients. At the last follow-up, 35% of cases were symptom-free (pharmacological remission 24%, remission without treatment 11%). The more severe the disease at the first observation and at the maximal worsening of symptoms, the lower was the proportion of remissions. Steroids were given in 54% and immunosuppressants in 18%. Thymectomy was performed in 72%, mostly in women, younger than age 40, and with generalized MG.

Thymectomy seemed to improve the course of the disease, mostly in patients operated on shortly after diagnosis and those with generalized mild-to-moderate disease and with a normally involuted thymus. MG was lethal in 4% of patients, principally men, older than 40, in grade 3 or worse at first observation, with a short history of disease, and with thymona.

AGE  

 

Clinical characteristics and prognosis of myasthenia gravis in older people.

Evoli A, Batocchi AP, Minisci C, Di Schino C, Tonali P.

Institute of Neurology, Catholic University, Roma, Italy.

J Am Geriatr Soc 2000 Nov;48(11):1442-8 Abstract quote

OBJECTIVES: To investigate the characteristics of myasthenia gravis (MG) in older people and to evaluate the benefits of immunosuppressive treatments at this age.

BACKGROUND: Myasthenia gravis in older adults has not been extensively studied. In patients with disease onset after the age of 60, treatment mainly relies on medical therapy because thymectomy is generally not performed unless a thymoma is present.

METHODS: Of 837 myasthenic patients followed since 1978, we identified 172 cases with onset after age 60. All patients were treated with anticholinesterases. In the decade from 1978 to 1988, immunosuppressive therapy was performed mainly with corticosteroids (prednisone); since 1989, azathioprine alone or, more often, associated with prednisone, has been increasingly used in MG patients. Long-term outcome was evaluated in 149 cases with follow-up longer than 1 year. Remission, pharmacological remission, and marked improvement with reduction in drug dosage were considered good results.

RESULTS: Patients older than age 60 at onset of the disease were 20.5% of our series, male/female ratio was 1.9, age at onset ranged from 61 to 86 years, 87.2% patients had generalized disease, thymoma was detected in 37 patients (21.5%). Of 149 cases with sufficient follow-up data, 9 were in remission, 111 achieved good results, 3 died of MG, and 120 required immunosuppressive therapy at some time. Sixty-seven patients had been treated with prednisone for 0.5-16 years (mean, 5 years); good results were recorded in 51 patients (76.1%) and severe side effects in 12 (17.9%). Forty-six patients had received combined therapy with prednisone and azathioprine for 1 to 12 years (mean, 3.9 years); good results were recorded in 41 patients (89.1%) and severe side effects in six (19.5%). Seven patients had been treated with azathioprine alone for 1 to 4 years (mean, 2.3 years) with good results in five and with no side effects.

CONCLUSIONS: The prognosis of MG in older people seems to be favorable, although full remission is rare and MG weakness, treatment side effects, and associated thymoma can contribute to mortality rate. In our experience, the combined therapy with prednisone and azathioprine was more effective than prednisone alone, and steroid-related side effects were more frequent than those related to azathioprine.


Myasthenia gravis in the elderly: a hospital based study.

Antonini G, Morino S, Gragnani F, Fiorelli M.

Department of Neurological Sciences, University of Rome La Sapienza, Italy.

Acta Neurol Scand 1996 Apr;93(4):260-2 Abstract quote

To evaluate clinical characteristics and outcome of myasthenia gravis (MG) in aged patients (> 60yrs), we retrospectively reviewed a continuous series of 122 myasthenic patients observed from January 1968 through December 1994. Patients with congenital, neonatal, or penicillamine-induced myasthenia were excluded. Twenty-five subjects (20%) were > 60yrs. The male/female ratio was 3:2; 20% of patients had an ocular form and 86% were seropositive. Mediastinum CT scan revealed thymic changes in 14%.

During the first five years of disease, 60% of patients with ocular form progressed towards a generalized form and 15% had clinical relapses. At the time of their last visit, 40% of patients were asymptomatic and 60% had improved on medication. No patient died because of myasthenia-related causes.

This study shows that MG in aged patients is characterized by prevalence in males, low frequency of ocular forms, low frequency of positive mediastinum CT which suggests low frequency of thymomas, high frequency of progression of ocular forms, and good response to corticosteroid therapy.


Early-onset myasthenia gravis: clinical characteristics and response to therapy.

Batocchi AP, Evoli A, Palmisani MT, Lo Monaco M, Bartoccioni M, Tonali P.

Institute of Neurology, Catholic University, Rome, Italy.

Eur J Pediatr 1990 Nov;150(1):66-8 Abstract quote

We studied 59 children with myasthenia gravis (MG). Disease onset was pre-pubertal in 26 patients and post-pubertal in 33. The male to female ratio was 0.62 in the early- and 0.17 in the late-onset groups. The frequency of ocular MG was higher in patients with prepubertal onset.

Patients with generalized MG generally showed a good response to thymectomy and corticosteroid therapy proved effective with no major side-effects. In our experience early-onset MG has the same course as in adult life.

We recommend thymectomy for generalized disease in childhood, except in very young children on account of possible long-term effects on immunological development. Immunosuppressive therapy should be considered in severely affected patients who do not respond adequately to other therapies.

THYMOMA  


Prognostic significance of thymomas in patients with myasthenia gravis.

de Perrot M, Liu J, Bril V, McRae K, Bezjak A, Keshavjee SH.

Division of Thoracic Surgery, Toronto General Hospital, Ontario, Canada.

 

Ann Thorac Surg 2002 Nov;74(5):1658-62 Abstract quote

BACKGROUND: The presence of thymoma may be a negative prognostic factor with respect to the outcome of myasthenia gravis (MG).

METHODS: Of 122 consecutive patients with MG undergoing thymectomy between August 1994 and September 2000, 37 had a thymoma. Postoperative radiation was administered to all patients with stage II thymoma and higher. To determine differences in presentation and outcome, thymoma patients were compared with patients with atrophic (n = 49) or hyperplastic (n = 36) thymus gland on final pathology.

RESULTS: Thymoma patients were significantly older (52 +/- 14 vs 36 +/- 15 years, p < 0.0001) and included a significantly higher proportion of males (54% vs 28%, p = 0.006) than patients without thymoma. However, the preoperative Osserman grade and the duration of symptoms before surgery were not significantly different between groups. Mean follow-up after thymectomy was not significantly different between patients with or without thymoma (32 +/- 23 vs 37 +/- 19 months, respectively, p = 0.3). At last follow-up, the proportion of asymptomatic patients (63% vs 70%, respectively, p = 0.5) and the mean Osserman grade (0.6 +/- 0.9 vs 0.5 +/- 0.9, respectively, p = 0.6) were similar in both groups. In addition, the rate of complete remission reached 36% at 5 years in patients with or without thymoma (p = 0.8).

CONCLUSIONS: Although myasthenic patients with thymoma are significantly older and include a greater proportion of males, the overall outcome, including the rate of complete remission, was similar between patients with or without thymoma. Therefore, the presence of a thymoma should not necessarily be viewed as a negative prognostic factor regarding recovery from myasthenia gravis.

TREATMENT  
INTRAVENOUS IMMUNOGLOBULIN  


Intravenous immunoglobulin monotherapy in long-term treatment of myasthenia gravis.

Wegner B, Ahmed I.

Trinity Lutheran Hospital, 64108, Kansas City, MO, USA


Clin Neurol Neurosurg 2003 Jan;105(1):3-8 Abstract quote

OBJECTIVE: To investigate effectiveness of long-term treatment of myasthenia gravis (MG) with intravenous immunoglobulin (IVIG).

BACKGROUND: There are no definitive studies showing effectiveness of IVIG therapy in long-term treatment of MG. Most studies have investigated the acute treatment of MG with IVIG. We describe our experience with long-term treatment of MG with IVIG in six patients.

METHODS: Acute treatment of MG by IVIG therapy has been well established in the literature. We describe six patients who were treated on a long-term basis with IVIG therapy. All of these patients had positive acetylcholine receptor antibody titers. They all received initial infusion for 5 days of IVIG at a dose of 400 mg/kg/day followed by maintenance therapy of 400 mg/kg for 1 day every 3-4 months. These patients were followed for 2 years. All other medications, including prednisone and cholingeric drugs such as Mestinon, were gradually weaned. For the last years, each of these patients maintained better than functional class 2 on an average of 1.5-2.2+/-0.5 grades on the University of Virginia modification of Ossermann's classification scale for MG. They were solely treated with IVIG infusion every 3-4 months without any other concomitant medications. Three of the patients had previously undergone thymectomies. None of the patients noticed any worsening in their scores on the University of Virginia modification of Ossermann's classification worse than Grade II in the last 2 years. There were no complications related to IVIG therapy, and all patients tolerated a single infusion of IVIG every 3-4 months at 400 mg/kg for 1 day.

\RESULTS: Our study demonstrates that IVIG maintenance is effective treatment of MG in selected patients and it is well tolerated.

CONCLUSIONS: IVIG therapy is a convenient, effective therapy when used selectively for treatment of MG on a long-term basis without any significant side effects.

Randomized, controlled trial of intravenous immunoglobulin in myasthenia gravis.

Wolfe GI, Barohn RJ, Foster BM, Jackson CE, Kissel JT, Day JW, Thornton CA, Nations SP, Bryan WW, Amato AA, Freimer ML, Parry GJ; Myasthenia Gravis-IVIG Study Group.

Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75390-8897,USA.

Muscle Nerve 2002 Oct;26(4):549-52 Abstract quote

We initiated a randomized, double-blinded, placebo-controlled trial of intravenous immunoglobulin (IVIG) treatment in myasthenia gravis (MG). Patients received IVIG 2 gm/kg at induction and 1 gm/kg after 3 weeks vs. 5% albumin placebo.

The primary efficacy measurement was the change in the quantitative MG Score (QMG) at day 42. Fifteen patients were enrolled (6 to IVIG; 9 to placebo) before the study was terminated because of insufficient IVIG inventories. At day 42, there was no significant difference in primary or secondary outcome measurements between the two groups.

In a subsequent 6-week open-label study of IVIG, positive trends were observed.

PLASMAPHARESIS  


Immunoglobulin treatment versus plasma exchange in patients with chronic moderate to severe myasthenia gravis.

Ronager J, Ravnborg M, Hermansen I, Vorstrup S.

Department of Neurology, Neuroscience Center, National University Hospital, Copenhagen, Denmark.

Artif Organs 2001 Dec;25(12):967-73 Abstract quote

The purpose of this study was to compare the efficacy of high-dose intravenous immunoglobulin (IVIG) treatment with plasma exchange in patients suffering from moderate to severe myasthenia gravis (MG) in a stable phase. There are no controlled studies comparing IVIG with plasma exchange in patients who despite immunosuppressive treatment have persistent incapacitating MG symptoms.

This was a controlled crossover study. Twelve patients with generalized moderate to severe MG on immunosuppressive treatment for at least 12 months were included. The patients were evaluated clinically using a quantified MG clinical score (QMGS) before and at follow-up visits after each treatment. One week after the treatments, the patients who received plasma exchange treatment showed a significant improvement in QMGS compared to baseline but although some improvement was seen after IVIG this did not reach statistical significance. Four weeks after both plasma exchange and IVIG treatments, there was a significant improvement in QMGS compared to baseline. One week and 4 weeks after treatment, no significant difference between the 2 treatments was found.

Both treatments have a clinically significant effect 4 weeks out in patients with chronic MG, but the improvement has a more rapid onset after plasma exchange than after IVIG.

THYMECTOMY  


Thymectomy in Myasthenia Gravis. Response, Complications, and Associated Conditions.

Remes-Troche JM, Tellez-Zenteno JF, Estanol B, Garduno-Espinoza J, Garci;a-Ramos G.

Departamento de Medicina Interna, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, INCMNSZ, Mexico City, Mexico

 

Arch Med Res 2002 Nov;33(6):545-551 Abstract quote

Thymectomy is considered the most effective treatment for achieving sustained improvement as well as remission in patients with myasthenia gravis (MG), and most neurologists favor the use of this procedure.

The main focus of many current studies is to determine response-predicting factors.Clinical records of 152 patients with an established diagnosis of MG who underwent thymectomy at our institution were reviewed.

The purpose was to evaluate outcome of surgical management for MG and prognostic factors that influence that outcome.The majority of patients were women (119 of 152); mean age was 32.10 +/- 14.42 years, while time elapsed from diagnosis to surgery was 20.67 +/- 19.7 months. Transsternal thymectomy was performed on 113 patients and transcervical on 39. Forty percent of patients achieved remission and 28% showed improvement; with this, a good response to thymectomy was seen in 68% of patients (n = 103). The most important variables associated with remission were <60 years of age, <2 years of preoperative symptoms, and use of pyridostigmine at low doses. Factors related with poor response were >60 years of age, preoperative Osserman stage other than II, use of high doses of pyridostigmine, use of corticosteroids, and presence of thymic atrophy or thymoma in histopathologic analyses. There was no mortality, although 20 patients (13%) presented complications.

Mexican patients with MG undergoing thymectomies show improvement and remission rates similar to those reported by other studies. Age, length of symptoms, thymic pathology, and medications appear to be predictors of response to thymectomy for MG.



Analysis of thymectomy for myasthenia gravis in older patients: a 20-year single institution experience.

Abt PL, Patel HJ, Marsh A, Schwartz SI.

Department of Surgery, The University of Rochester School of Medicine and Dentistry, NY, USA.

J Am Coll Surg 2001 Apr;192(4):459-64 Abstract quote

BACKGROUND: Thymectomy has become recognized as an integral element in the care of the patient with myasthenia gravis. Although the number of elderly patients with myasthenia is substantial, little data exist demonstrating the efficacy and morbidity of thymectomy in this population.

STUDY DESIGN: We retrospectively analyzed 126 cervicomediastinal thymectomies performed at a single university hospital from 1980 to 1998. Patients 55 years or older were compared with those less than 55. Efficacy was measured by determining the change in Osserman score, the rate of remission during followup, and the reduction in medication requirements after thymectomy.

RESULTS: Older patients (n = 28) had similar Osserman scores (p = 0.8) and similar rates of complete and partial remission as the younger group (n = 98) at a mean +/- SEM followup of 58 +/- 5 months. The two groups did not differ in the number (p = 0.4) and doses of medications used to control myasthenic symptoms after operation. Older age was associated with an increased length of hospitalization (13.8 +/- 3.2 days versus 9.7 +/- 0.6 days, p = 0.05) and a higher incidence of reintubation, and longer ventilatory support (2.6 +/- 1.3 days versus 0.1 +/- 0.1 days, p = 0.001).

CONCLUSIONS: Increased age does not alter the outcomes of thymectomy for myasthenia gravis. Older patients can expect to have similar responses and require a similar number of postoperative medications as younger patients, but with a higher short-term morbidity.


Myasthenia gravis: a retrospective study comparing thymectomy to conservative treatment.

Werneck LC, Cunha FM, Scola RH.

Internal Medicine Department, Hospital de Clinicas, Universidade Federal do Parana, Curitiba, Brazil.

Acta Neurol Scand 2000 Jan;101(1):41-6 Abstract quote

OBJECTIVES: To study the effectiveness of thymectomy (TY) in a group of patients with myasthenia gravis compared to a group of patients submitted to conservative treatment (CT) at a similar clinical stage.

METHODS: Among 153 patients with myasthenia gravis, we paired 28 patients who underwent TY, with 28 cases under CT. The following data were analyzed: gender, age, and age at the beginning of symptoms, illness duration, follow-up time and type of medical treatment. There was no statistical difference between these 2 groups. The mean time for TY was 2.5 (0.2-13) years after the onset of the disease. The cases were evaluated through a functional scale at the beginning and at the end of the study.

RESULTS: We found complete remission in 15 cases (TY 6, CT 9), improved (normal life with or without minimal symptoms and with or without medication) 9 cases (TY 8, CT 1), improved with partial control and minimal limitation 32 cases (TY 14, CT 18), and poor control 2 cases (TY 2). No death was found in this group.

CONCLUSION: There was no statistical difference between the conservative treatment and thymectomy groups, regarding remission or improvement. Furthermore TY done in the first year of the disease or latter, did not change the final outcome.


Prognostic factors for myasthenia gravis treated by thymectomy: review of 61 cases.

Nieto IP, Robledo JP, Pajuelo MC, Montes JA, Giron JG, Alonso JG, Sancho LG.

Department of General and Digestive Surgery, La Paz University Hospital, Madrid, Spain.

Ann Thorac Surg 1999 Jun;67(6):1568-71 Abstract quote

BACKGROUND: Medical treatment for myasthenia gravis (MG) involves the use of anticholinesterase agents, immunosuppressive drugs, plasmapheresis, and gamma-globulin. However, these agents result in a complete clinical remission rate as low as 15%. As a consequence, thymectomy, preferably by transsternal approach, has become increasingly accepted as an efficacious procedure for MG, with reported complete clinical remission rates as high as 80%.

METHODS: We have the clinical records of 61 patients diagnosed with MG at La Paz University Hospital, Madrid, Spain, from January 1977 to December 1994. All patients underwent thymectomy. The purpose of this investigation was to determine the major prognostic factors predicting MG outcome after operation.

RESULTS: Our results indicate that patients with a length of the disease from onset to operation shorter than 8 months have the best prognosis. Ossermann stages I and III are also associated with higher complete clinical remission rates. In contrast, neither age nor sex were found to be significantly related to MG outcome after thymectomy, although female patients have better prognosis than men, and the younger the patient the more likely is complete clinical remission. Pathologic findings after the operation were not found to be of prognostic value either.

CONCLUSIONS: We conclude that thymectomy is a beneficial procedure for MG patients, with a complete clinical remission rate of 46% at 5 years postoperatively in our series. Therefore we advocate thymectomy for MG patients as early as possible in the course of disease because time elapsed from diagnosis to operation is the main determinant of the outcome.

 

Early and late results after thymectomy in myasthenia gravis: a retrospective study [correction of analysis]

Klein M, Heidenreich F, Madjlessi F, Granetzny A, Dauben HP, Schulte HD, Gams E.

Department of Thoracic and Cardiovascular Surgery, Heinrich-Heine Universitat, Dusseldorf, Germany.

Thorac Cardiovasc Surg 1999 Jun;47(3):170-3 Abstract quote

BACKGROUND: This study aims to evaluate the early and late outcome of patients treated by surgery for myasthenia gravis and the diagnostic value of the Besinger Score, which is based on a correlation of severity of symptoms with specific antibodies to acetylcholine receptors, in the follow-up investigation after surgical therapy.

METHODS: Between June 1984 and April 1992 thoracotomy was performed in 51 myasthenia gravis cases at our department. The retrospective analysis considered patients with (n = 13) or without thymoma (n = 38). The Besinger score was used to describe the severity of disease preoperatively and up to 5 years postoperatively.

RESULTS: The Besinger score fell continually post surgery. Changes in relative serum concentrations of antibodies were similar to the Besinger score. Five years after thymectomy complete remission was diagnosed in 40% of the patients. The required dosage of pyridostigmine had fallen by two thirds after 5 years. Patients with follicular hyperplasia had significantly higher remission rates than those with thymoma.

CONCLUSIONS: Surgery for myasthenia gravis is successful. The Besinger score well quantifies the severity of the disease.


Thymectomy for myasthenia gravis: a 27-year experience.

Venuta F, Rendina EA, De Giacomo T, Della Rocca G, Antonini G, Ciccone AM, Ricci C, Coloni GF.

Department of Thoracic Surgery, University of Rome La Sapienza, Italy. f

Eur J Cardiothorac Surg 1999 May;15(5):621-4 Abstract quote

OBJECTIVE: Thymectomy is considered an effective therapeutic option for patients with myasthenia gravis (MG). We reviewed our 27-year experience with surgical treatment of MG with respect to long-term results and factors affecting outcome.

METHODS: Between 1970 and 1997, we performed 232 thymectomies for MG. Fifteen patients were lost to follow-up; the remaining 217 form the object of our study. Sixty-two patients (28.4%) had thymoma. Myasthenia was graded according to a modified Osserman classification: 51 patients (23.5%) were in class I, 81(37.3%) in class IIA, 52 (24%) in class IIB, 26 (12%) in class III and seven (3.2%) in class IV. Mean duration of symptoms before the operation was 12+/-10 months. Fifty-eight thymectomies for thymoma were performed through a median sternotomy and four through a clamshell incision. Forty-six thymectomies for non-thymomatous MG were performed through a standard cervicotomy, 101 procedures through a partial upper sternal-splitting incision and eight through a complete median sternotomy.

RESULTS: Operative mortality was 0.92% (two patients). After a mean follow-up of 119 months, 71% of all patients improved their clinical status (25% without medications and asymptomatic; 46% with a reduction of medications and/or clinically improved); 39 (18%) have a stable disease with no clinical modifications; 12 (5%) presented a deterioration of their clinical status with worse symptoms, required more medications, or both. Thirteen patients (6%) died because of MG (mean survival 34.3+/-3.6 months). The presence of a thymoma negatively influenced the prognosis. Younger patients showed a more favorable outcome as well as patients with a shorter duration of symptoms before the operation; patients with lower classes of myasthenia showed a higher rate of remission.

CONCLUSIONS: Thymectomy is effective in the management of patients with MG at all stages with low morbidity. Patients with thymoma present a less favorable outcome.

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