- Email: [email protected]
Effects of thymectomy on late-onset myasthenia gravis without thymoma
Clinical Neurology and Neurosurgery 109 (2007) 858–861
Effects of thymectomy on late-onset myasthenia gravis without thymoma Naoki Kawaguchi a,∗ , Satoshi Kuwabara a , Yuko Nemoto a , Toshio Fukutake a , Kimiyoshi Arimura b , Mitsuhiro Osame b , Takamichi Hattori a b
a Department of Neurology, Chiba University, Graduate School of Medicine, 1-8-1 Inohna, Chuo-ku, Chiba 260-8670, Japan Department of Neurology and Geriatrics, Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Received 23 March 2007; received in revised form 3 August 2007; accepted 4 August 2007
Abstract Objectives: This study aims to investigate whether thymectomy is beneficial for late-onset (>50 years) myasthenia gravis patients with no thymoma, particularly for those with mild generalized weakness. Patients and methods: A total of 34 patients were included in the study. The clinical course and long-term outcomes over 2 years were reviewed in 20 patients who underwent thymectomy and in 14 without thymectomy. Results: Of the 34 patients, 20 (59%) underwent thymectomy. Thymectomized patients had more severe disability at entry than nonthymectomized patients, but outcome measures did not significantly differ between the two patient groups. Moreover, subgroup analyses including 22 patients with mild generalized weakness at entry showed that the thymectomized group (n = 10) showed a greater percentage of clinical remission (no symptoms; 50% versus 17%; p = 0.11) and a lower frequency of the presence of generalized symptoms (30% versus 75%; p < 0.05) than the non-thymectomized group (n = 12) at the end of follow-up (means 9.6 years after onset). Conclusions: Thymectomy is a potentially effective treatment for late onset, non-thymomatous patients with mild generalized myasthenia gravis. © 2007 Elsevier B.V. All rights reserved. Keywords: Myasthenia gravis; Late onset; Thymectomy; Thymoma; Outcome
1. Introduction Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission generally mediated by antibodies specific to the human nicotinic acetylcholine receptor [1,2]. Autoimmune MG is probably the best understood of the human autoimmune diseases, and our knowledge of its pathogenesis and treatment has increased [2,3]. In the 1970s, thymectomy became an increasingly accepted form of therapy, and today, thymectomy is one of the most frequently employed treatments for MG. However, a recent evidence-based review failed to show conclusive benefits of thymectomy in non-thymomatous MG patients and only ∗
Corresponding author. Tel.: +81 43 222 7171x5411; fax: +81 43 226 2160. E-mail address: [email protected] (N. Kawaguchi). 0303-8467/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2007.08.006
recommended thymectomy as an option to increase the probability of remission or improvement [4]. Another issue of controversy regarding thymectomy is whether it is beneficial in late-onset MG patients without thymoma. To evaluate the current status of thymectomy and the outcome of MG patients with mild severity of the disease and no thymoma, we reviewed the clinical course and outcomes of such patients in a retrospective cross-sectional multi-centre survey conducted in Japan.
2. Patients and methods The survey was performed between 1999 and 2000, and a total of 470 patients with MG were recruited from 19 tertiary medical centres, which belonged to the Research Group for Neuroimmunological Disease supported by the Ministry
N. Kawaguchi et al. / Clinical Neurology and Neurosurgery 109 (2007) 858–861
of Health, Labour and Welfare of Japan [5]. Clinical profiles, treatments, and outcomes were reviewed from medical records. The clinical grade of disease severity was evaluated according to the Myasthenia Gravis Foundation of America (MGFA) clinical classification: class 1, ocular muscle weakness only; class 2, mild generalized weakness; class 3, moderate generalized weakness; class 4, severe generalized weakness; class 5, intubation required; MGFA postintervention status [6]. From this survey, we selected 34 patients with late-onset (age of onset > 50 years) MG and no thymoma. Secondly, we performed subgroup analyses including only patients with MGFA class 2 for the following two reasons: (1) in order to compare the effects of treatment between the two patient groups, we considered it better to standardize the severity of MG at the time of treatment initiation, and (2) the aim of this study was to investigate whether thymectomy is effective for ‘mild’ disease. Whether or not the patients were treated with thymectomy depended on the judgement of the evaluating neurologist. For statistical analyses, differences in frequency of the presence of generalized symptoms were tested with Fisher’s exact test, and differences in the median MGFA class were tested with the Mann–Whitney’s test.
859
Surgery was preferentially performed in patients with greater disability; the median MGFA class was greater in the thymectomy group than in the non-thymectomy group (Mann–Whitney’s test, p = 0.059), and the proportion of patients with MGFA class 3 or more was greater in the thymectomy group than in the non-thymectomy group (Fisher’s exact probability test, p = 0.035). Thymectomy was performed in 10 (91%) of the 11 patients with MGFA class 3 or more but in only 10 (45%) of the 22 patients with MGFA class 2. Although the patients in the thymectomy group had more severe disability at entry than those in the nonthymectomy group, the MGFA scores at the end of follow-up were not significantly different between the thymectomized and the non-thymectomized patients. Irrespective of whether or not the patients underwent thymectomy, most were administered the following medications: 32 patients (94%) were administered cholinesterase inhibitors, 25 (74%), corticosteroids; 4 (12%), other immunosuppressive agents. After treatment, nine (26%) patients were in remission (no symptoms; MGFA score 0); however, some patients continued to take medication.
3.2. The subgroup of patients with mild generalized weakness 3. Results 3.1. All patients A total of 34 well-documented cases were obtained. The cases comprised 13 men and 21 women with a mean age of onset of 63.7 years (range, 50–78 years). The mean disease duration was 8.5 years (range, 2–25 years). Thymectomy was performed in 20 (59%) of the 34 patients. Table 1 shows the clinical profiles and treatments in patients with thymectomy and those without thymectomy.
The subgroup analysis included 22 patients with MGFA class 2. The patients comprised 10 men and 12 women with a mean age of onset of 63.9 years (range, 52–78 years). The mean disease duration was 9.6 years (range, 2–25 years). Thymectomy was performed in 10 (45%) of the 22 patients; we divided the patients into two groups: one group treated with thymectomy and the other without thymectomy. Table 2 compares the clinical profiles and treatments between patients with thymectomy and without thymectomy. The thymectomy group had a slightly younger mean
Table 1 Clinical profiles of MG patients With thymectomy (n = 20)
Without thymectomy (n = 20)
Total (n = 34)
Onset age of onset, years, mean (range) Male:female Disease duration, years Positive anti-AChR antibody
61 (50–77) 10:10 9.2 18 (90%)
67 (55–78) 3:11 7.6 11 (79%)
64 (50–78) 13:21 8.5 29 (85%)
MGFA score before treatment MGFA class, median (range) MGFA III or more
2.5 (2–3)* 10 (50%)**
2 (2–5) 2 (14%)
2 (2–5) 12 (35%)
MGFA score at the end of follow-up Remission MGFA II MGFA III or more
6 (30%) 10 (50%) 0 (0%)
3 (21%) 8 (57%) 2 (14%)
9 (26%) 18 (53%) 2 (6%)
Other treatment Cholinesterase inhibitor Corticosteroid Other immunosuppressant
19 (95%) 17 (70%) 2 (10%)
13 (93%) 8 (57%) 2 (14%)
32 (94%) 25 (74%) 4 (12%)
*p = 0.059; **p = 0.035, compared with non-thymectomized patients.
860
N. Kawaguchi et al. / Clinical Neurology and Neurosurgery 109 (2007) 858–861
Table 2 Clinical profiles of MG patients with mild severity (pretreatment severity, MGFA class II)
Onset age of onset, years, mean (range) Male:female* Disease duration (years) Peak MGFA class, median (range) Positive anti-AChR antibody Other treatment Cholinesterase inhibitor Corticosteroid Other immunosuppressant *
With thymectomy (n = 10)
Without thymectomy (n = 12)
61 (52–67)
66 (55–78)
7:3 11.7 2 (2–5)
3:9 7.8 2 (2–4)
9 (90%)
9 (75%)
10 (100%) 7 (70%) 1 (10%)
11 (92%) 6 (50%) 1 (8%)
p < 0.05.
age of onset (not significant statistically) and included more male patients than the non-thymectomy group (p = 0.04). As described in the methods section, all the thymectomized and non-thymectomized patients had MGFA class 2. Of the 10 thymectomized patients, myasthenic crisis after thymectomy was recognized in 3 (30%) patients, and they were treated mainly with plasmapheresis and corticosteroids. Almost all of the patients included in this study were administered medications; the percentages of patients treated with cholinesterase inhibitors, corticosteroids, or other immunosuppressants did not differ significantly between the two groups. Table 3 shows the MGFA classes at the end of the followup period in 22 patients. The mean follow-up period was 11.7 years for thymectomized patients and 7.8 years for nonthymectomized patients. At the end of the follow-up period, 5 (50%) of the thymectomized patients and 2 (17%) of the non-thymectomized patients showed minimal manifestations (no symptoms of functional limitations from MG); however, some patients continued to take medication (p = 0.11). Two (20%) of the thymectomized patients had only ocular symptoms (class 1), and 3 (30%) still had weakness of bulbar or limb muscles (class 2). On the other hand, one (8%) of the non-thymectomized patients had only ocular symptoms (class 1), seven (58%) still had mild weakness of bulbar or limb muscles (class 2), and two (17%) of the patients Table 3 MGFA clinical classes at the end of the follow-up With thymectomy (n = 10) No symptoms 5 (50%) Class I 2 (20%) Class II 3 (30%) Class III 0 (0%) Classes IV and V 0 (0%) Classes II–V 3 (30%)* MGFA: Myasthenia Gravis Foundation of America. * p = 0.045.
had moderate generalized weakness (class 3). Generalized symptoms were observed in 3 out of the 10 thymectomized patients and in 9 out of the 12 non-thymectomized patients (Fisher’s exact probability test, p = 0.045). Two (29%) of seven thymectomized patients and one (17%) of six nonthymectomized patients were free from steroids at the end of the follow-up, the percentages of patients did not differ significantly between the two groups. In seven patients in whom thymus histology was available, two had hyperplasia and five had normal thymus.
4. Discussion Our results showed that the prognosis of late-onset MG patients without thymoma was generally favourable. Thymectomy was likely to be performed in MG patients with moderate weakness before treatment. For the subgroup of the MG patients with mild weakness, thymectomy appeared to be effective since minimal manifestations (no symptoms) were observed in 50% of the thymectomized patients compared with 17% of the non-thymectomized patients. Moreover, only 30% of the thymectomized patients as against 75% of the nonthymectomized patients had mild generalized symptoms at the end of the follow-up period. This study is retrospective with a relatively small number of patients, and it has a number of limitations. First, age and gender were not sufficiently matched between the two patient groups. Secondly, the selection of only patients with MGFA class 2 did not permit the analyses of the outcomes of lateonset MG patients in general. Previous studies suggest no significant benefit from thymectomy in late-onset MG in general [7–9]; Romi et al. compared the clinical grade of 21 thymectomized and 22 non-thymectomized late-onset MG patients up to 5 years; no dramatic effects of thymectomy were observed; however, the study suggested that the presence of anti-striated muscle antibodies, such as anti-titin antibody, is associated with the prognosis of late-onset MG patients [7]. It has been suggested that the thymus in elderly patients is atrophic with fatty degeneration, and thymectomy may not have beneficial effects [10]. Our results show that thymectomy is a potentially effective treatment. The reasons for the discrepancy in the results between our study and those of previous studies are unknown. Future prospective studies involving a larger number of patients will be required to reach a conclusion.
Without thymectomy (n = 12) 2 (16.7%) 1 (8.3%) 7 (58.3%) 2 (16.7%) 0 (0%) 9 (75%)
Acknowledgments This study was supported by a grant for Neuroimmunological Diseases from the Ministry of Health, Labour and Welfare of Japan. We thank the members of The Study Group for Myasthenia Gravis in Japan for collecting the clinical data [5].
N. Kawaguchi et al. / Clinical Neurology and Neurosurgery 109 (2007) 858–861
References [1] Schluep M, Willcox N, Vincent A, Dhoot GK, Newsom-Davis J. Acetylcholine receptors in human thymic myoid cells in situ: an immunohistological study. Ann Neurol 1987;22:212–22. [2] Ciafaloni E, Sanders DB. Advances in myasthenia gravis. Curr Neurol Neurosci Rep 2002;2:89–95. [3] Kissel JT, Franklin GM, and the Quality Standards Subcommittee of the American Academy of Neurology. Treatment of myasthenia gravis. A call to arms. Neurology 2000;55:3–4. [4] Gronseth GS, Barohn R. Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-based review). Report from the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000;55:7–15. [5] Kawaguchi N, Kuwabara S, Nemoto Y, Fukutake T, Satomura Y, Arimura K, et al. Treatment and outcome of myasthenia gravis: ret-
[6]
[7]
[8] [9] [10]
861
rospective multi-center analysis of 470 Japanese patients, 1999–2000. J Neurol Sci 2004;224:43–7. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America; Jaretzki III A, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, et al. Myasthenia gravis; recommendations for clinical research standards. Neurology 2000;55:16– 23. Romi F, Gilhus NE, Varhaug JE, Myking A, Skeie GO, Aarli JA. Thymectomy and anti-muscle autoantibodies in late-onset myasthenia gravis. Eur J Neurol 2002;9:55–61. Aarli JA. Late-onset myasthenia gravis: a changing scene. Arch Neurol 1999;56:25–7. Romi F, Gilhus NE, Aarli JA. Myasthenia gravis: disease severity and prognosis. Acta Neurol Scand Suppl 2006;183:24–5. Perlo VP, Arnason B, Castleman B. The thymus gland in elderly patients with myasthenia gravis. Neurology 1975;25:294–5.
Effects of thymectomy on late-onset myasthenia gravis without thymoma Naoki Kawaguchi a,∗ , Satoshi Kuwabara a , Yuko Nemoto a , Toshio Fukutake a , Kimiyoshi Arimura b , Mitsuhiro Osame b , Takamichi Hattori a b
a Department of Neurology, Chiba University, Graduate School of Medicine, 1-8-1 Inohna, Chuo-ku, Chiba 260-8670, Japan Department of Neurology and Geriatrics, Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima, Japan
Received 23 March 2007; received in revised form 3 August 2007; accepted 4 August 2007
Abstract Objectives: This study aims to investigate whether thymectomy is beneficial for late-onset (>50 years) myasthenia gravis patients with no thymoma, particularly for those with mild generalized weakness. Patients and methods: A total of 34 patients were included in the study. The clinical course and long-term outcomes over 2 years were reviewed in 20 patients who underwent thymectomy and in 14 without thymectomy. Results: Of the 34 patients, 20 (59%) underwent thymectomy. Thymectomized patients had more severe disability at entry than nonthymectomized patients, but outcome measures did not significantly differ between the two patient groups. Moreover, subgroup analyses including 22 patients with mild generalized weakness at entry showed that the thymectomized group (n = 10) showed a greater percentage of clinical remission (no symptoms; 50% versus 17%; p = 0.11) and a lower frequency of the presence of generalized symptoms (30% versus 75%; p < 0.05) than the non-thymectomized group (n = 12) at the end of follow-up (means 9.6 years after onset). Conclusions: Thymectomy is a potentially effective treatment for late onset, non-thymomatous patients with mild generalized myasthenia gravis. © 2007 Elsevier B.V. All rights reserved. Keywords: Myasthenia gravis; Late onset; Thymectomy; Thymoma; Outcome
1. Introduction Myasthenia gravis (MG) is an autoimmune disorder of neuromuscular transmission generally mediated by antibodies specific to the human nicotinic acetylcholine receptor [1,2]. Autoimmune MG is probably the best understood of the human autoimmune diseases, and our knowledge of its pathogenesis and treatment has increased [2,3]. In the 1970s, thymectomy became an increasingly accepted form of therapy, and today, thymectomy is one of the most frequently employed treatments for MG. However, a recent evidence-based review failed to show conclusive benefits of thymectomy in non-thymomatous MG patients and only ∗
Corresponding author. Tel.: +81 43 222 7171x5411; fax: +81 43 226 2160. E-mail address: [email protected] (N. Kawaguchi). 0303-8467/$ – see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2007.08.006
recommended thymectomy as an option to increase the probability of remission or improvement [4]. Another issue of controversy regarding thymectomy is whether it is beneficial in late-onset MG patients without thymoma. To evaluate the current status of thymectomy and the outcome of MG patients with mild severity of the disease and no thymoma, we reviewed the clinical course and outcomes of such patients in a retrospective cross-sectional multi-centre survey conducted in Japan.
2. Patients and methods The survey was performed between 1999 and 2000, and a total of 470 patients with MG were recruited from 19 tertiary medical centres, which belonged to the Research Group for Neuroimmunological Disease supported by the Ministry
N. Kawaguchi et al. / Clinical Neurology and Neurosurgery 109 (2007) 858–861
of Health, Labour and Welfare of Japan [5]. Clinical profiles, treatments, and outcomes were reviewed from medical records. The clinical grade of disease severity was evaluated according to the Myasthenia Gravis Foundation of America (MGFA) clinical classification: class 1, ocular muscle weakness only; class 2, mild generalized weakness; class 3, moderate generalized weakness; class 4, severe generalized weakness; class 5, intubation required; MGFA postintervention status [6]. From this survey, we selected 34 patients with late-onset (age of onset > 50 years) MG and no thymoma. Secondly, we performed subgroup analyses including only patients with MGFA class 2 for the following two reasons: (1) in order to compare the effects of treatment between the two patient groups, we considered it better to standardize the severity of MG at the time of treatment initiation, and (2) the aim of this study was to investigate whether thymectomy is effective for ‘mild’ disease. Whether or not the patients were treated with thymectomy depended on the judgement of the evaluating neurologist. For statistical analyses, differences in frequency of the presence of generalized symptoms were tested with Fisher’s exact test, and differences in the median MGFA class were tested with the Mann–Whitney’s test.
859
Surgery was preferentially performed in patients with greater disability; the median MGFA class was greater in the thymectomy group than in the non-thymectomy group (Mann–Whitney’s test, p = 0.059), and the proportion of patients with MGFA class 3 or more was greater in the thymectomy group than in the non-thymectomy group (Fisher’s exact probability test, p = 0.035). Thymectomy was performed in 10 (91%) of the 11 patients with MGFA class 3 or more but in only 10 (45%) of the 22 patients with MGFA class 2. Although the patients in the thymectomy group had more severe disability at entry than those in the nonthymectomy group, the MGFA scores at the end of follow-up were not significantly different between the thymectomized and the non-thymectomized patients. Irrespective of whether or not the patients underwent thymectomy, most were administered the following medications: 32 patients (94%) were administered cholinesterase inhibitors, 25 (74%), corticosteroids; 4 (12%), other immunosuppressive agents. After treatment, nine (26%) patients were in remission (no symptoms; MGFA score 0); however, some patients continued to take medication.
3.2. The subgroup of patients with mild generalized weakness 3. Results 3.1. All patients A total of 34 well-documented cases were obtained. The cases comprised 13 men and 21 women with a mean age of onset of 63.7 years (range, 50–78 years). The mean disease duration was 8.5 years (range, 2–25 years). Thymectomy was performed in 20 (59%) of the 34 patients. Table 1 shows the clinical profiles and treatments in patients with thymectomy and those without thymectomy.
The subgroup analysis included 22 patients with MGFA class 2. The patients comprised 10 men and 12 women with a mean age of onset of 63.9 years (range, 52–78 years). The mean disease duration was 9.6 years (range, 2–25 years). Thymectomy was performed in 10 (45%) of the 22 patients; we divided the patients into two groups: one group treated with thymectomy and the other without thymectomy. Table 2 compares the clinical profiles and treatments between patients with thymectomy and without thymectomy. The thymectomy group had a slightly younger mean
Table 1 Clinical profiles of MG patients With thymectomy (n = 20)
Without thymectomy (n = 20)
Total (n = 34)
Onset age of onset, years, mean (range) Male:female Disease duration, years Positive anti-AChR antibody
61 (50–77) 10:10 9.2 18 (90%)
67 (55–78) 3:11 7.6 11 (79%)
64 (50–78) 13:21 8.5 29 (85%)
MGFA score before treatment MGFA class, median (range) MGFA III or more
2.5 (2–3)* 10 (50%)**
2 (2–5) 2 (14%)
2 (2–5) 12 (35%)
MGFA score at the end of follow-up Remission MGFA II MGFA III or more
6 (30%) 10 (50%) 0 (0%)
3 (21%) 8 (57%) 2 (14%)
9 (26%) 18 (53%) 2 (6%)
Other treatment Cholinesterase inhibitor Corticosteroid Other immunosuppressant
19 (95%) 17 (70%) 2 (10%)
13 (93%) 8 (57%) 2 (14%)
32 (94%) 25 (74%) 4 (12%)
*p = 0.059; **p = 0.035, compared with non-thymectomized patients.
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N. Kawaguchi et al. / Clinical Neurology and Neurosurgery 109 (2007) 858–861
Table 2 Clinical profiles of MG patients with mild severity (pretreatment severity, MGFA class II)
Onset age of onset, years, mean (range) Male:female* Disease duration (years) Peak MGFA class, median (range) Positive anti-AChR antibody Other treatment Cholinesterase inhibitor Corticosteroid Other immunosuppressant *
With thymectomy (n = 10)
Without thymectomy (n = 12)
61 (52–67)
66 (55–78)
7:3 11.7 2 (2–5)
3:9 7.8 2 (2–4)
9 (90%)
9 (75%)
10 (100%) 7 (70%) 1 (10%)
11 (92%) 6 (50%) 1 (8%)
p < 0.05.
age of onset (not significant statistically) and included more male patients than the non-thymectomy group (p = 0.04). As described in the methods section, all the thymectomized and non-thymectomized patients had MGFA class 2. Of the 10 thymectomized patients, myasthenic crisis after thymectomy was recognized in 3 (30%) patients, and they were treated mainly with plasmapheresis and corticosteroids. Almost all of the patients included in this study were administered medications; the percentages of patients treated with cholinesterase inhibitors, corticosteroids, or other immunosuppressants did not differ significantly between the two groups. Table 3 shows the MGFA classes at the end of the followup period in 22 patients. The mean follow-up period was 11.7 years for thymectomized patients and 7.8 years for nonthymectomized patients. At the end of the follow-up period, 5 (50%) of the thymectomized patients and 2 (17%) of the non-thymectomized patients showed minimal manifestations (no symptoms of functional limitations from MG); however, some patients continued to take medication (p = 0.11). Two (20%) of the thymectomized patients had only ocular symptoms (class 1), and 3 (30%) still had weakness of bulbar or limb muscles (class 2). On the other hand, one (8%) of the non-thymectomized patients had only ocular symptoms (class 1), seven (58%) still had mild weakness of bulbar or limb muscles (class 2), and two (17%) of the patients Table 3 MGFA clinical classes at the end of the follow-up With thymectomy (n = 10) No symptoms 5 (50%) Class I 2 (20%) Class II 3 (30%) Class III 0 (0%) Classes IV and V 0 (0%) Classes II–V 3 (30%)* MGFA: Myasthenia Gravis Foundation of America. * p = 0.045.
had moderate generalized weakness (class 3). Generalized symptoms were observed in 3 out of the 10 thymectomized patients and in 9 out of the 12 non-thymectomized patients (Fisher’s exact probability test, p = 0.045). Two (29%) of seven thymectomized patients and one (17%) of six nonthymectomized patients were free from steroids at the end of the follow-up, the percentages of patients did not differ significantly between the two groups. In seven patients in whom thymus histology was available, two had hyperplasia and five had normal thymus.
4. Discussion Our results showed that the prognosis of late-onset MG patients without thymoma was generally favourable. Thymectomy was likely to be performed in MG patients with moderate weakness before treatment. For the subgroup of the MG patients with mild weakness, thymectomy appeared to be effective since minimal manifestations (no symptoms) were observed in 50% of the thymectomized patients compared with 17% of the non-thymectomized patients. Moreover, only 30% of the thymectomized patients as against 75% of the nonthymectomized patients had mild generalized symptoms at the end of the follow-up period. This study is retrospective with a relatively small number of patients, and it has a number of limitations. First, age and gender were not sufficiently matched between the two patient groups. Secondly, the selection of only patients with MGFA class 2 did not permit the analyses of the outcomes of lateonset MG patients in general. Previous studies suggest no significant benefit from thymectomy in late-onset MG in general [7–9]; Romi et al. compared the clinical grade of 21 thymectomized and 22 non-thymectomized late-onset MG patients up to 5 years; no dramatic effects of thymectomy were observed; however, the study suggested that the presence of anti-striated muscle antibodies, such as anti-titin antibody, is associated with the prognosis of late-onset MG patients [7]. It has been suggested that the thymus in elderly patients is atrophic with fatty degeneration, and thymectomy may not have beneficial effects [10]. Our results show that thymectomy is a potentially effective treatment. The reasons for the discrepancy in the results between our study and those of previous studies are unknown. Future prospective studies involving a larger number of patients will be required to reach a conclusion.
Without thymectomy (n = 12) 2 (16.7%) 1 (8.3%) 7 (58.3%) 2 (16.7%) 0 (0%) 9 (75%)
Acknowledgments This study was supported by a grant for Neuroimmunological Diseases from the Ministry of Health, Labour and Welfare of Japan. We thank the members of The Study Group for Myasthenia Gravis in Japan for collecting the clinical data [5].
N. Kawaguchi et al. / Clinical Neurology and Neurosurgery 109 (2007) 858–861
References [1] Schluep M, Willcox N, Vincent A, Dhoot GK, Newsom-Davis J. Acetylcholine receptors in human thymic myoid cells in situ: an immunohistological study. Ann Neurol 1987;22:212–22. [2] Ciafaloni E, Sanders DB. Advances in myasthenia gravis. Curr Neurol Neurosci Rep 2002;2:89–95. [3] Kissel JT, Franklin GM, and the Quality Standards Subcommittee of the American Academy of Neurology. Treatment of myasthenia gravis. A call to arms. Neurology 2000;55:3–4. [4] Gronseth GS, Barohn R. Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-based review). Report from the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2000;55:7–15. [5] Kawaguchi N, Kuwabara S, Nemoto Y, Fukutake T, Satomura Y, Arimura K, et al. Treatment and outcome of myasthenia gravis: ret-
[6]
[7]
[8] [9] [10]
861
rospective multi-center analysis of 470 Japanese patients, 1999–2000. J Neurol Sci 2004;224:43–7. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America; Jaretzki III A, Barohn RJ, Ernstoff RM, Kaminski HJ, Keesey JC, Penn AS, et al. Myasthenia gravis; recommendations for clinical research standards. Neurology 2000;55:16– 23. Romi F, Gilhus NE, Varhaug JE, Myking A, Skeie GO, Aarli JA. Thymectomy and anti-muscle autoantibodies in late-onset myasthenia gravis. Eur J Neurol 2002;9:55–61. Aarli JA. Late-onset myasthenia gravis: a changing scene. Arch Neurol 1999;56:25–7. Romi F, Gilhus NE, Aarli JA. Myasthenia gravis: disease severity and prognosis. Acta Neurol Scand Suppl 2006;183:24–5. Perlo VP, Arnason B, Castleman B. The thymus gland in elderly patients with myasthenia gravis. Neurology 1975;25:294–5.