Stiff-man syndrome and variants: clinical course, treatments, and outcomes.
Stiff-man syndrome and variants: clinical course, treatments, and outcomes.
复制标题
僵人综合症及其变体：临床过程、治疗和结果。
作者：
MD Andrew McKeon;MD Maisha T. Robinson;MD Kathleen M. McEvoy;PhD Joseph Y. Matsumoto;MD Vanda A. Lennon;PhD J. Eric Ahlskog;MD Sean J. Pittock PhD;Dr. McKeon;Robinson McEvoy;Lennon Matsumoto
背景
关于僵硬人综合征（SMS）（经典形式或其变体）的发生率或长期治疗反应和结局的信息很少。
目的
全面描述SMS患者队列的特征。
设计
观察性研究。
设置
马约诊所，罗切斯特，明尼苏达州。
患者
99例经典SMS与该疾病变体的患者，谷氨酸脱羧酶65 kD同种型（GAD 65）抗体血清阳性和血清阴性。
主要观察指标
1984年1月至2008年12月期间的神经学、自身免疫性、血清学和肿瘤学结果;治疗和结局。
结果
中位随访时间为5年（范围：0 - 23年）。79例患者（59例经典SMS，19例部分SMS，1例进行性脑脊髓炎伴强直和肌阵挛[PERM]）GAD 65抗体血清阳性。其中67%（79人中的53人）患有至少1种并存的自身免疫性疾病，4%（79人中的3人）患有癌症。GAD 65抗体在典型SMS患者中的初始评估值（中位数，623 nmol/L）显著高于部分SMS患者（中位数，163 nmol/L）（P <.001）。初始GAD 65抗体值与末次随访兰金评分呈正相关（P = 0.03）。在20例GAD 65抗体血清阴性的患者中（6例为经典SMS，12例为部分SMS，2例为PERM），15%（20例中的3例）至少有1种共存的自身免疫性疾病，25%（20例中的5例）患有癌症（3例为两性霉素自身免疫性和乳腺癌，2例为霍奇金淋巴瘤）。排除PERM患者，除1例患者外，所有患者均在使用至少1种γ-氨基丁酸药物（通常为地西泮）后持续改善;经典SMS患者的中位剂量为40.0 mg/d。34例接受免疫治疗（静脉注射免疫球蛋白、硫唑嘌呤、泼尼松、吗替麦考酚酯或环磷酰胺）的患者中有14例（41%）出现了额外的改善。25例随访时间延长的患者中有16例（64%）仍能走动。
结论
识别经典SMS与变体非常重要，因为适当的治疗可以改善大多数患者的症状。根据解剖学范围和GAD 65抗体血清状态进行分类提供了重要的诊断和预后信息。
BACKGROUND
Little information is available about the incidence of stiff-man syndrome (SMS) (the classic form or its variants) or about long-term treatment responses and outcomes.
OBJECTIVE
To comprehensively describe the characteristics of a cohort of patients with SMS.
DESIGN
Observational study.
SETTING
Mayo Clinic, Rochester, Minnesota.
PATIENTS
Ninety-nine patients with classic SMS vs variants of the disorder, both glutamic acid decarboxylase 65 kD isoform (GAD65) antibody seropositive and seronegative.
MAIN OUTCOME MEASURES
Neurological, autoimmune, serological, and oncological findings; treatments; and outcomes between January 1984 and December 2008.
RESULTS
The median follow-up duration was 5 years (range, 0-23 years). Seventy-nine patients (59 having classic SMS, 19 having partial SMS, and 1 having progressive encephalomyelitis with rigidity and myoclonus [PERM]) were GAD65 antibody seropositive. Sixty-seven percent (53 of 79) of them had at least 1 coexisting autoimmune disease, and 4% (3 of 79) had cancer. GAD65 antibody values at initial evaluation were significantly higher among patients with classic SMS (median value, 623 nmol/L) than among patients with partial SMS (median value, 163 nmol/L) (P < .001). The initial GAD65 antibody value was positively correlated with the last follow-up Rankin score (P = .03). Among 20 patients who were GAD65 antibody seronegative (6 with classic SMS, 12 with partial SMS, and 2 with PERM), 15% (3 of 20) had at least 1 coexisting autoimmune disease, and 25% (5 of 20) had cancer (3 with amphiphysin autoimmunity and breast carcinoma and 2 with Hodgkin lymphoma). Excluding patients with PERM, all patients but 1 had sustained improvements with at least 1 γ-aminobutyric acid agent, usually diazepam; the median dosage for patients with classic SMS was 40.0 mg/d. Additional improvements occurred among 14 of 34 patients (41%) who received immunotherapy (intravenous immune globulin, azathioprine, prednisone, mycophenolate mofetil, or cyclophosphamide). Sixteen of 25 patients (64%) with extended follow-up duration remained ambulatory.
CONCLUSIONS
Recognition of classic SMS vs variants is important because appropriate therapy improves symptoms in most patients. Classification by anatomical extent and by GAD65 antibody serostatus gives important diagnostic and prognostic information.