| Myasthenia gravis(MG) is determined as an autoimmune disease mediated by anti-acetylcholine receptor antibodies(ACh R-Abs), in which the synaptic transmission across the neuro- muscular junction(NMJ) is impaired, somewhat leading to weakness and fatigability of striated muscles with recovery with rest. Based on the involoved muscles, MG is individed into ocular MG(OMG) and generalized MG(GMG). When weakness is limited to the extraocular muscles, orbicularis oculi, and levator palpebrae superioris, it is considered to be OMG; however, when systemic involvement of skeletal muscles is present, a diagnosis of GMG should be made and its prognosis becomes worse. In GMG, a respiratory failure secondary to respiratory muscle paralysis might occur, endangering the lives of patients. Epidemiological studies have shown that MG occurs worldwide in which both men and women can be suffered; meanwhile, it is also a heterogenetic disease that can be influenced by geography, ethnicity and gender. The clinical features of OMG in China are yet to be fully analyzed. It has been indicated that 85% of MG patients begin with a pure paralysis of extraocular muscles, in whom about 50% of patients may progress to GMG within six months after onset, 80% of patients within one year, and 90% of patients after three years, leading to a poor prognosis for patients and a tremendous pressure for families and society. Therefore, it is of a positive practical significance to explore the clinical indicators predicting a transformation from OMG to GMG, identify and treat the patients at high risk for generalized development as soon as possible, and achieve a good prognosis. ObjectiveTo retrospectively analyze the clinical features of OMG in China; to carry out the subgroup comparison of clinical features of OMG based on different age at onset and neurophysiological findings; to explore predictors for generalized development in OMG patients. MethodsWe reviewed all MG patients admitted to Department of Neurology, Tangdu Hospital of the Fourth Military Medical University between June 2008 and June 2012, and enrolled the patients with an initial diagnosis of OMG. All the clinical parameters including gender, age at onset, initial ocular symptoms, response to neostigmine test, electrophysiologic findings, thymic status by computed tomography(CT), and thyroid function were collected and the clinical features of OMG in China was analyzed. The last follow-up visit was carried out on June 2013 by face-to-face interview or by telephone and data on generalized development was recorded. The possible predictors for generalized development in OMG patients were explored by a logistic regression method. ResultsA total of 392 patients with a initial diagnosis of OMG from 22 provinces and municipalities were included in this study. There were 210 men and 182 women, and male-to-female ratio was 1.2:1. The age at onset ranged from 9 months to 81 years, with a median age at onset of 20 years. No significant differences in the median age at onset and patient distribution in different age stage were observed between male and female patients. Both men and women had the first peak incidence before the age of 15 years(186/392; 47.4%), and a second peak incidence of the ages between 50 and 60 years with a male preponderance. The initial symptom of 366 patients(93.4%) was or contained ptosis, with a precedency of unilateral paralysis(269 cases) than bilateral paralysis(97 cases). An initial symptom of pure ptosis was seen in 265 cases(67.6%), pure diplopia in 26 cases(6.6%), ptosis with diplopia in 101 cases(25.8%). There was no significant differences of patient distribution in different initial ocular symptoms between males and females(P = 0.439). Limitation of ocular movement was observed in 199 eyes from 125 patients, with the most type of total ophthalmoplegia accounting for 30.7% of all the affected eyes, followed by pure abduction limitation(15.6%) and pure supraduction limitation(10.6%). In the involved 199 eyes, abduction limitation was seen in 65.8%, supraduction limitation in 58.8%, adduction limitation in 58.3%, and infraduction limitation in 48.7%. A neostigmine test was performed in 308 cases and a positive response was seen in 295 cases(95.8%), with a comparable positive rate between male and female patients. The positive rate of low-frequency repetitive nerve stimulation(RNS) on facial nerves, axillary nerves and ulnar nerves was 32.4%, 20.2% and 2.5%, respectively. No significant differences in the positive RNS rate of each detected nerve were found between male and female patients. There were 31 of 169 patients(18.3%) combined with abnormal thyroid function, with hyperthyroidism in 16 cases, subclinical hyperthyroidism in 7 cases, hypothyroidism in 2 cases, and subclinical hypothyroidism in 6 cases. There were 58 of 280 OMG patients(20.7%) combined with thymic abnormalities on chest CT scanning, with thymoma in 36 cases, thymic hyperplasia in 15 cases, non-degraded thymus in 7 cases. There were 223 patients who completed the final follow-up visit, with a response rate of 56.9%. No significant differences in all the clinical parameters of interest were observed between 223 cases and 392 cases. Subgroup analysis showed that the positive rate of axillary nerve RNS testing was significantly higher in adult-onset MOG than that in juvenile OMG(30.8% vs 8.3%; P = 0.032). Compared with patients with a negative response to facial nerve RNS, patient with a positive response had an increased positive rate on axillary nerve RNS testing. Similarly, the patient with a positive response to axillary nerve RNS had a markedly increased positive rate on facial nerve RNS testing, when compared with patients with a negative response to axillary nerve RNS. Generalized development occurred in 38 of 223 patients(17.0%). The cumulative probability of achieving generalization was significantly higher, respectively, in sdult-onset OMG than in juvenile OMG, in facial nerve RNS-positve patients than in RNS-negative patients, and in axillary nerve RNS-positive patients than in RNS-negative patients. Compared with juvenile OMG patients, adult-onset patients had a shorter duration of GMG conversion(P = 0.0139). A multivariate logistic regression analysis was used to evaluate the associations between the clinical parameters of interest and generalized development. We found that age at onset(Odds ratio [OR] = 1.023, 95% confidence interval [CI] 1.006-1.041, P = 0.007) was associated with generalized development; moreover, the significant association was found for duraton of disease(OR = 0.603, 95%CI 0.365-0.850, P = 0.019), and positive facial nerve RNS(OR = 2.826, 95%CI 1.045-5.460, P = 0.038). ConclusionOMG in China exhibit a unique clinical features including male preponderance, pure ptosis as the commonest initial symptom, total ophthalmoplegia as the most frequent type of limitation of ocular movement, the most frequent involvement of lateral rectus muscle, a high positive rate of neostigmine test, the highest positive rate on facial nerves RNS testing, hyperthyroidism as the most frequent type when combined with abnormal thyroid function, and thymoma as the most common type when combined with thymic abnormalities on chest CT scanning. A higher percentage of positive facial nerve and axillary nerve RNS response appear simultaneously. Age at onset, duration of disease, and facial nerve RNS findings are predictors for the conversion of OMG to GMG. Adult-onset, shorter duration, and facial nerve RNS-positive OMG patients have a higher risk of generalized development. |
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