title: Response to treatment of myasthenia gravis according to clinical subtype.
abstract: BACKGROUND
  We have previously reported using two-step cluster analysis to classify myasthenia gravis (MG) patients into the following five subtypes: ocular MG; thymoma-associated MG; MG with thymic hyperplasia; anti-acetylcholine receptor antibody (AChR-Ab)-negative MG; and AChR-Ab-positive MG without thymic abnormalities. The objectives of the present study were to examine the reproducibility of this five-subtype classification using a new data set of MG patients and to identify additional characteristics of these subtypes, particularly in regard to response to treatment.
  
  
  METHODS
  A total of 923 consecutive MG patients underwent two-step cluster analysis for the classification of subtypes. The variables used for classification were sex, age of onset, disease duration, presence of thymoma or thymic hyperplasia, positivity for AChR-Ab or anti-muscle-specific tyrosine kinase antibody, positivity for other concurrent autoantibodies, and disease condition at worst and current. The period from the start of treatment until the achievement of minimal manifestation status (early-stage response) was determined and then compared between subtypes using Kaplan-Meier analysis and the log-rank test. In addition, between subtypes, the rate of the number of patients who maintained minimal manifestations during the study period/that of patients who only achieved the status once (stability of improved status) was compared.
  
  
  RESULTS
  As a result of two-step cluster analysis, 923 MG patients were classified into five subtypes as follows: ocular MG (AChR-Ab-positivity, 77%; histogram of onset age, skewed to older age); thymoma-associated MG (100%; normal distribution); MG with thymic hyperplasia (89%; skewed to younger age); AChR-Ab-negative MG (0%; normal distribution); and AChR-Ab-positive MG without thymic abnormalities (100%, skewed to older age). Furthermore, patients classified as ocular MG showed the best early-stage response to treatment and stability of improved status, followed by those classified as thymoma-associated MG and AChR-Ab-positive MG without thymic abnormalities; by contrast, those classified as AChR-Ab-negative MG showed the worst early-stage response to treatment and stability of improved status.
  
  
  CONCLUSIONS
  Differences were seen between the five subtypes in demographic characteristics, clinical severity, and therapeutic response. Our five-subtype classification approach would be beneficial not only to elucidate disease subtypes, but also to plan treatment strategies for individual MG patients.
authors.affiliation: Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Akaishi
authors.affiliation: Department of Neurology, Sendai Medical Center, Sendai, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Neurology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Tomihiro
authors.initials: T
authors.lastname: Imai
authors.affiliation: Department of Neurology, Sapporo Medical University, Sapporo, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Tsuda
authors.affiliation: Department of Neurology, Hokkaido Medical Center, Sapporo, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Minami
authors.affiliation: Department of Neurology, Hanamaki General Hospital, 4-28 Kajoh-chou, Hanamaki, 025-0075, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Nagane
authors.affiliation: Department of Neurology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Akiyuki
authors.initials: A
authors.lastname: Uzawa
authors.affiliation: Department of Neurology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kawaguchi
authors.affiliation: Department of Neurology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Masuda
authors.affiliation: Department of Neurology, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Konno
authors.affiliation: Department of Neurology, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Neurological Therapeutics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Murai
authors.affiliation: Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Aoki
authors.affiliation: Department of Neurology, Hanamaki General Hospital, 4-28 Kajoh-chou, Hanamaki, 025-0075, Japan. kutsugi@s4.dion.ne.jp.
authors.forename: Kimiaki
authors.initials: K
authors.lastname: Utsugisawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000401:mortality* / Q000473:pathology; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013945:Thymoma / Q000150:complications; D013953:Thymus Neoplasms / Q000150:complications; D055815:Young Adult
keywords: Classification; Cluster analysis; Myasthenia; Onset age; Treatment