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 »  Abstract
 »  Introduction
 »  Material and methods
 »  Results
 »  Discussion
 »  References

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Year : 2000  |  Volume : 48  |  Issue : 4  |  Page : 343-6

A study of myasthenia gravis in patients with and without thymoma.


Departments of Neurology and Endocrine Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India.

Correspondence Address:
Departments of Neurology and Endocrine Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India.

  »  Abstract

This study was undertaken to compare the clinical, neurophysiological, radiological and prognostic features of myasthenia gravis with and without thymoma. 37 patients with myasthenia gravis (27 males, 10 females), with age range of 4.5 to 72 (mean 39) years, were managed at a tertiary care centre in India. Four patients were below 15 years of age and 6 above 55 years. Most of the patients were in stage II (34). There were 2 patients in stage III and 1 in stage I. 27 patients underwent thymectomy. Thymoma was detected in 10 cases. The decrement in patients with thymoma ranged between 11 and 62% (mean 27.9%) and nonthymoma group 10-75% (mean 28%). CT scan of thorax revealed mediastinal mass in 5 out of 10 cases of thymoma and 2 out of 27 patients without thymoma. Outcome of myasthenia gravis with thymoma was worse than without thymoma at 1 year followup. Severity of illness, extent of decrement, lack of facilitation, duration of illness and age of the patients were not related to the outcome. It is concluded the clinical and neurophysiological changes in myasthenia gravis with and without thymoma do not differ. However, patients with thymoma have a worse outcome.

How to cite this article:
Roy A, Kalita J, Misra U K, Kar D, Agarwal A, Misra S K. A study of myasthenia gravis in patients with and without thymoma. Neurol India 2000;48:343


How to cite this URL:
Roy A, Kalita J, Misra U K, Kar D, Agarwal A, Misra S K. A study of myasthenia gravis in patients with and without thymoma. Neurol India [serial online] 2000 [cited 2021 May 6];48:343. Available from: https://www.neurologyindia.com/text.asp?2000/48/4/343/1503




   »   Introduction Top

Thymus has a central role in the pathogenesis of myasthenia gravis.[1] The patients with myasthenia gravis may have thymic hyperplasia, atrophy or thymoma. The clinical picture of these subsets of myasthenia gravis is rather uniform and does not significantly differ from each other, although the treatment of the patients with thymoma and those without it differ significantly.[2] The management of myasthenia gravis has been considerably influenced by modern imaging techniques, advances in critical care, surgery, plasmapheresis and immunosuppresion. A comparison of clinical picture and outcome of myasthenia gravis patients with and without thymoma has been reported.[3],[4],[5] The clinical picture of 10 patients with thymoma and their outcome has been recently reported from India.[6] We, however, could not get a study comparing myasthenia gravis patients with and without thymoma from India. In the present study we report a comparative account of clinical, radiological and neurophysiological features of consecutive patients with myasthenia gravis with and without thymoma.


   »   Material and methods Top

During 1991 to 1998, 40 patients with myasthenia gravis were managed at Sanjay Gandhi Postgraduate Institute, Lucknow, which is a tertiary care super speciality hospital. The diagnosis of myasthenia gravis was based on history of fatigability, improvement following rest, a positive prostigmine test and significant decremental response at low rate repetitive nerve stimulation atleast in 2 muscles. All the patients underwent a detailed neurological examination. History of associated autoimmune disorders such as rheumatoid arthritis, diabetes mellitus, thyroiditis, alopecia areata, vitiligo etc was taken. The severity of myasthenia gravis was graded according to Osserman's classification. The prostigmine test was carried out in all the patients by injecting 1.5 mg neostigmine intramuscularly along with 0.6 mg atropine. Arm stretch time, leg raising time, number of sit ups, lateral gaze time, lid raising time, nasal twang on counting aloud and single breath count were recorded prior to injection and 15, 30 and 60 min after the injection. The blood pressure and pulse rate were also recorded. The clinical improvement exceeding 50% was regarded as positive prostigmine test. Repetitive nerve stimulation test was carried out in abductor [digiti] minimi, deltoid and nasalis by stimulating ulnar nerve at wrist, Erb's point and facial nerve respectively. Six supramaximal stimuli were delivered at 3 Hz at rest, 10 sec and 3 min after 10 sec of maximal voluntary contraction of the target muscle. A decrement exceeding 10% between first and fifth response was considered abnormal.
The other investigations included haematological, blood chemistry, thyroid hormone profile, rheumatoid factor and anti ds DNA. Plain radiograph of chest in PA and lateral view was carried out in all the patients. CT scan thorax, MRI or both were also carried out. Patients with generalised myasthenia within 15 to 55 years of age were subjected to extended trans-sternal thymectomy under general anaesthesia. Corticosteroids were not prescribed and if a patient received prednisolone earlier, it was withdrawn before surgery. Plasmapheresis, if indicated, was carried out to tide over the crisis before surgery or post operatively. After surgery, the patients were prescribed acetyl cholinesterase inhibitor such as pyridostigmine or prostigmine or both. Corticosteroids, azathioprine, chemotherapy or radiotherapy were given as per indication. The patients were regularly followed up at 3 monthly intervals. The outcome was defined on the basis of clinical status at the end of one year. Return to previous occupation with or without acetyl cholinesterase inhibitor was regarded as good recovery. Use of immunosuppressive agents or 600 mg or more of pyridostigmine daily was classified as poor recovery.


   »   Results Top

During 1991-1998, a total 40 patients with myasthenia were seen. Three of these were excluded because they suffered from congenital myasthenia. The present data is, therefore, based on 37 patients with myasthenia gravis. Their mean age was 39 (range 4.5-72) years. There were 10 females in this group. Four patients were below 15 years and 6 above 55 years. Majority of the patients at the time of presentation were in stage II (34); only 2 patients being in stage III and one in stage I. Two patients had respiratory paralysis requiring artificial ventilation at the time of admission. Bulbar involvement necessitated nasogastric feeding in 15 patients. 5 others needed ventilatory support in the later part of their illness. The duration of symptoms ranged between 10 days and 48 months (mean 7 months). Prostigmine test and repetitive nerve stimulation study was positive in all the patients. The extent of decrement ranged between 10 and 75% (mean 28%). Post-exercise facilitation was present in 22 patients and absent in 15. Extent of highest decrement was not associated with severity of illness (X2=2.7; df=3, NS). Lack of post tetanic facilitation was also not associated with severity of illness (X2=5.89, df=3, NS) and outcome (X2=3.17, df=2, NS).
On chest radiograph, mediastinal mass was seen in 2 patients only. Computerised radiography of thorax revealed evidence of thymic enlargement in 7 patients [Figure - 1]. Thymectomy was carried out in 27 patients. The remaining 10 patients were either children (4) or above 55 years (6). The histology of thymus revealed thymoma in 10, thymic hyperplasia in 11 and normal thymus in 6 patients. Post operatively all the patients received cholinesterase inhibitors such as pyridostigmine and or neostigmine or both. Corticosteroids and azathioprine were prescribed in 12 patients and only azathioprine in one patient who was diabetic and above 55 years of age. Out of the 12 patients on corticosteroid and azathioprine, 5 were above 55 years who did not undergo thymectomy and 7 received post operative immunosuppression because of poor response after 6 months of thymectomy. All the 10 patients with thymoma received radiotherapy and also received combination chemotherapy comprising of cyclophosphamide, doxorubicin and cisplatin. In our study, 3 patients died, 1 of whom had thymoma. This patient had alopecia areata and expired after 6 months of surgery.
In the thymoma group, 6 patients had poor and 3 had good outcome. In nonthymoma group two patients died. One died due to post operative septicaemia and the other due to associated cirrhosis and hepatic failure. Five patients had poor and 20 had good outcome. The outcome was not related to stage of myasthenia gravis on admission (X2=9.0, df=6, NS). All the patients who died had presented in stage II A. Out of 18 patients in stage IIA, 13 had good and 2 poor recovery. Out of 16 patients in stage IIB, 8 had good and 8 had poor recovery. Out of two stage III patients one had good and the other had poor recovery. One year outcome was significantly worse in thymoma compared to nonthymoma group (X2=6.56, df=2, p<0.05). The one year outcome of MG was however not related to age of the patient (X2=3.09, df=2, NS) and duration of illness (X2=4.0, df=2, NS). The comparison of clinical investigation and outcome of myasthenia gravis patients with and without thymoma is summarised in [Table I]. The thymoma patients were males, not significantly older and had more pronounced weakness than the myasthenics without thymoma.


   »   Discussion Top

In this study of myasthenia gravis, 27% patients had thymoma and all of them had poorer outcome at one year followup as compared to the non thymoma group. This incidence is higher compared to the reported incidence of thymoma (10 to 15%).[7] We have only one patient with ocular myasthenia which may be due to referral bias as these patients might have been referred to ophthalmology department. Our centre being a tertiary care centre, only advanced cases might have been referred. Myasthenia gravis is generally considered to be commoner in females.[8] Thymoma, however, is equally common in both men and women and is most common in fifth and sixth decade. In our study, however, all the patients with thymoma were males, even those without thymoma had a male predominance; two-thirds being males. This may be due to a genetic preference or due to socioeconomic structure of Indian society.
The role of radiology in the diagnosis of thymoma needs special mention. Thymic enlargement was seen in chest radiographs of 2 patients and CT scan of thorax in 7 patients. In 5 of our patients thymoma was diagnosed per-operatively as their CT scans were normal. The limitation of CT scan in the diagnosis of thymoma has been reported. Although CT scan is the investigation of choice for visualising thymus, thymoma can not be diagnosed with high level of confidence in patients below 40 years. This is due to difficulty in differentiating normal thymus or hyperplasia from thymoma. In a study of 19 patients with myasthenia gravis, who underwent thymectomy, CT scan was accurate in detecting 9 true thymic masses but could not distinguish thymoma from nonthymomatous masses.[9] In our study the limitation of CT scan in the diagnosis of thymoma could be due to younger age of our patients. The imaging by CT scan and MRI is not only used for the diagnosis of thymic enlargement but also in defining its extent and tissue invasion in adjacent viscera. It is helpful in planning surgery and follow up of these patients.
The extent of decrement in our study was not related to severity of illness. In the literature, however, it has been mentioned that lack of post exercise facilitation suggests a lack of reserve and is consistent with more severe illness.[10] Insistence of 10 sec exercise period may result in exhaustion of relatively advanced cases. In such cases, the duration of exercise may be shortened. We however gave 10 sec exercise to all the patients. Most of our patients were in stage II, which may be responsible for lack of correlation between decrement and clinical severity of myasthenia gravis. In our study, stage of myasthenia gravis at the time of presentation was not related to outcome, whereas presence of thymoma had definite relation. A number of authors have reported a less favourable survival of myasthenic patients with thymoma compared to those without it.[11-13] It has been suggested that patients with thymoma show greater severity and progression, and lesser response to therapeutic measures. In the literature, the patients with thymoma have been reported to have a shorter duration of illness. Our results, however, do not support this notion. The duration and severity of illness in our study in both the groups of myasthenia gravis were comparable. This may be due to relatively small sample size. One of our patients had alopecia areata alongwith thymoma and died 6 months after thymectomy. Presence of alopecia areata in MG has been reported to be asssociated thymoma and poor outcome.[14]
It can be concluded from our study that the clinical presentation, severity of illness and neurophysiological findings are comparable in myasthenics with and without thymoma. The outcome of thymoma patients was significantly worse compared to nonthymoma patients. Our results are based on a small sample size, but this limitation is offset by detailed investigations, uniform prospective evaluation and sequential followup.

 

  »   References Top

1.Hohlfeld R, Wekerle H : The role of thymus in myasthenia gravis. Advances in Neuroimmunology1994; 4 : 373-386.   Back to cited text no. 1    
2.Kodoma H, Yoshida I, Ohtani Y et al : Myasthenia gravis : an analysis of patients with postoperative crisis after thymectomy. Kyobu Geka 1995; 48 : 110-112.   Back to cited text no. 2    
3.Verley JM, Hollmann KH : Thymoma. A comparative study of clinical stages, histologic features and survival in 200 cases. Cancer 1985; 55 : 1074-1086.   Back to cited text no. 3    
4.Rowland LP, Lisak RP, Schotland DL et al : Myasthenic myopathy and thymoma. Neurology1973; 23 : 283-287.   Back to cited text no. 4    
5.Ohmi M, Ohuchi M : Recurrent thymoma in patients with myasthenia gravis. Ann Thorac Surg 1990; 50 : 243-247.   Back to cited text no. 5    
6.Pandit L, Rao SN : Thymomatous myasthenia gravis. J Assoc Physicians India1995; 43 : 543-545.   Back to cited text no. 6    
7.Wakata N, Fugioka T, Nishina M et al : Myasthenia gravis and invasive thymoma. A 20 year experience. Eur Neurol 1993; 33 : 115-120.   Back to cited text no. 7    
8.Beekman R, Kuks JB, Oosterhuis HJ : Myasthenia gravis : diagnosis and followup of 100 consecutive patients. J Neurol 1997; 244 : 112-118.   Back to cited text no. 8    
9.Brown LR, Mohm JR, Sheedy PF II et al : The value of computed tomography in myasthenia gravis. American Journal of Roentgenology1983; 235 : 140 : 31-35.   Back to cited text no. 9    
10.Oh SJ, Eslami N, Nishihira T et al : Electrophysiological and clinical correlation in myasthenia gravis. Ann Neurol 1998; 12 : 348-354.   Back to cited text no. 10    
11.Perlo VP, Poskenzer DC, Schwab RS et al : Myasthenia gravis : evaluation of treatment in 1355 patients. Neurology l996; 16 : 431-444.   Back to cited text no. 11    
12.Glob D, Arsura EL, Brunner NG et al : The course of myasthenia gravis and therapies affecting outcome. Ann N Y Acad Sci 1987; 505 : 472-499.   Back to cited text no. 12    
13.Evoli A, Batocchi AP, Provenzano C et al : Thymectomy in the treatment of myasthenia gravis : report of 247 patients. J Neurol 1988; 235 : 272-276.   Back to cited text no. 13    
14.Kubuta A, Komiyama A, Hasegawa O : Myasthenia gravis and alopecia areata. Neurology 1997; 48 : 774-775.   Back to cited text no. 14    

 

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