Spinal muscular atrophy: Survival pattern and functional status
Spinal muscular atrophy: Survival pattern and functional status
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DOI：
10.1542/peds.2004-0668
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发表时间：
2004-11-01
期刊：
影响因子：
8
通讯作者：
Ip, P
中科院分区：
文献类型：
--
作者：
Chung, BHY;Wong, VCN;Ip, P
目标。脊髓性肌萎缩症(SMA)很常见。华南地区的SMA患病率为1/53000。临床病程多种多样。SMA的传统分类包括发病年龄、死亡年龄、运动里程碑的完成情况和活动状态作为标准。没有包括任何患有SMA的儿童一生中最好的功能状态。随着医疗保健的进步，SMA患者的预期寿命和步行状态都得到了改善。本研究的目的是评估患有SMA的儿童的生存模式、活动状态和功能状态。SMA患者来自肯特公爵夫人儿童医院的神经肌肉诊所，这是一家大学附属医院，以及SMA在香港的家人。截至2002年9月，肯特公爵夫人儿童医院神经肌肉诊所和SMA登记家庭登记了102例SMA病例，并对83例患者进行了分析。其中39人被招募参加儿童功能独立性测量(WeeFIM)的管理，WeeFIM是我们先前为中国儿童验证的功能状态评估工具。SMA的诊断是通过临床病史、血清肌酶、肌电图、肌肉活检以及最近的分子研究来作出的。在香港，自1995年开始对幸存运动神经元基因进行分子测试。在我们的83名患者队列中，共有36名患者的诊断得到了分子分析的证实。我们采用了以前研究中的SMA分类，其中的标准是基于国际SMA联合会(1992)，并根据第59届欧洲神经肌肉中心国际研讨会进行了修改。由于只研究了有儿童期发病的SMA患者，所以我们的研究中没有包括任何IV型患者。对父母进行了访谈，并回顾了记录中的人口统计学和临床数据，包括发病年龄、性别、家族史、运动里程碑、疾病进展、运动功能丧失以及呼吸或延髓肌肉受累。我们将发病年龄定义为从医疗记录或父母对第一批虚弱迹象的描述中发现第一批异常明显的年龄，例如，达到某些运动里程碑或功能丧失的年龄。对于可行走状态，我们将“可行走”定义为能够行走100米，无论是在有卡尺或助行器的辅助下，还是在没有辅助的情况下。用Kaplan-Meier方法计算生存概率和剩余活动概率，得到精算生存曲线。在2002年9月的最后一次登记日期，使用WeeFIM对父母或主要照顾者进行了功能状态访谈。WeeFIM由3个领域组成：1)自我照顾，2)行动能力，3)认知。自理领域由8项组成，分别是进食、打扮、洗澡、穿衣(上身)、穿衣(下身)、如厕和排便管理。移动域包括5个项目：从椅子或轮椅转移、转移到厕所、转移到浴缸或淋浴、步行/轮椅/爬行距离、上下楼梯。认知领域评估理解、表达、社交、解决问题和记忆。评分从1到7(1=完全帮助，2=最大帮助，3=中度帮助，4=最小接触帮助，5=监督，6=修改后的独立性，7=完全独立)。WeeFIM总分最高为126分，其中生活自理、行动能力和认知能力得分最高分别为56分、35分和35分。对于I型SMA(n=22)，1、2、4、10和20年的生存概率分别为50%、40%、30%、30%和30%。II型SMA(n=26)1、2、4、10、20年生存率分别为100%、100%、100%、92%和92%。16名SMA I级患者和4名SMA II级患者死于心肺衰竭。5例存活的SMA-I患者均依赖呼吸机。所有SMA III患者在研究时都存活了下来。IIIa型患者发病后2、4、10和20年仍能行走的概率分别为100%、100%、81%和50%(发病年龄分别为90%、IIa型和IIa型患者和63%的IIIb型患者)。楼梯管理是实现所有类型SMA的独立性的主要障碍。认知领域表现最好，60%的SMA II型患者、78%的IIIa型SMA患者和90%的IIIb型SMA患者实现了功能独立。然而，除了IIIb型SMA外，很大一部分患者在解决问题方面仍然需要帮助或监督。I型和II型之间以及IIIa型和IIb型患者之间的WeeFIM评分差异有统计学意义。然而，II型和IIa型SMA患者在3个领域的WeeFIM总分或表现上没有显著差异。我们发现，与其他研究相比，SMA患者的存活率有所改善。大多数SMA患者在活动和自我护理领域都需要帮助或监督。随着医学进步导致生存率的提高，在指定的年龄评估最新的或有史以来最好的功能状态可能是SMA分类的重要标准。
Objective. Spinal muscular atrophy (SMA) is common. The prevalence of SMA in southern Chinese is 1 in 53 000. The clinical course is variable. The traditional classification of SMA includes age of onset, age of death, achievement of motor milestones, and ambulatory status as criteria. There was a lack of inclusion of the best lifetime functional status of any child with SMA. With the advances in medical care, the life expectancy and ambulatory status of patients with SMA have improved. The objective of this study was to assess the survival pattern, ambulatory status, and functional status of children with SMA.Methods. Patients with SMA were recruited from the neuromuscular clinic of the Duchess of Kent Children's Hospital, which is a university-affiliated hospital, and the Families of SMA in Hong Kong. By September 2002, 102 SMA cases had been registered in the Duchess of Kent Children's Hospital neuromuscular clinic and Families of SMA registry, and 83 patients were analyzed. Among them, 39 were recruited for the administration of Functional Independence Measure for Children (WeeFIM), an assessment tool for functional status that has been previously validated by us for Chinese children. The diagnosis of SMA was made from clinical history, serum muscle enzyme, electromyography, muscle biopsy, and, recently, by molecular studies. In Hong Kong, molecular tests of the survivor motor neuron gene was available since 1995. A total of 36 in our cohort of 83 patients had the diagnosis confirmed with molecular analyses. We adopted the classification of SMA from previous studies in which the criteria were based on the International SMA consortium ( 1992) with modifications according to the 59th European Neuromuscular Center International Workshops. As only SMA patients with childhood onset were studied, we did not include any type IV patients in our study. Parents were interviewed and records were reviewed for demographic and clinical data, including age of onset, gender, family history, motor milestones, disease progression, loss of motor function, and involvement of respiratory or bulbar muscles. We define the age of disease onset as the age in which the first abnormalities were obvious from the medical records or from the descriptions of the parents about the first signs of weakness, eg, age of achievement of certain motor milestones or loss of functions. For the ambulatory status, we define "being ambulatory" as having the ability to walk for 100 meters, either with assistance such as calipers or walkers or without assistance. Actuarial survival curves were obtained by using the Kaplan-Meier method for calculating survival probabilities and probabilities of remaining ambulatory. The parents or the chief caregivers were interviewed for functional status using WeeFIM at the last registered date in September 2002. The WeeFIM consists of 3 domains: 1) self-care, 2) mobility, and 3) cognition. The self-care domain consists of 8 items, namely eating, grooming, bathing, dressing ( upper body), dressing ( lower body), toileting, and bladder and bowel management. The mobility domain consists of 5 items: transfer from chair or wheelchair, transfer to toilet, transfer to tub or shower, walking/wheelchair/crawling distance, and moving up and down stairs. The cognition domain assesses comprehension, expression, social interaction, problem solving, and memory. A scoring scale from 1 to 7 was used (1 = total assistance, 2 = maximal assistance, 3 = moderate assistance, 4 = minimal contact assistance, 5 = supervision, 6 = modified independence, and 7 = complete independence). The maximum total WeeFIM score is 126, and the maximum score for self-care, mobility, and cognition are 56, 35, and 35, respectively.Results. For type I SMA (n = 22), the survival probabilities at 1, 2, 4, 10, and 20 years were 50%, 40%, 30%, 30%, and 30%, respectively. For type II SMA (n = 26), the survival probabilities at 1, 2, 4, 10, and 20 years were 100%, 100%, 100%, 92%, and 92%, respectively. Sixteen of the SMA I patients and 4 of the SMA II patients died of cardiorespiratory failure. The 5 surviving SMA I patients all were ventilator dependent. All SMA III patients were surviving at the time of study. The probability of remaining ambulatory at 2, 4, 10, and 20 years after onset was 100%, 100%, 81%, and 50% for type IIIa (age of onset 90% of SMA types I, II, and IIIa and in 63% of SMA type IIIb patients. Stair management was the major obstacle for independence in achieving mobility for all types of SMA. For the cognition domain, performance was the best among the 3 domains, and 60% of SMA type II, 78% of SMA type IIIa, and 90% of SMA type IIIb patients achieved functional independence. However, except for SMA type IIIb, a significant proportion of patients still need assistance or supervision in the area of problem solving. Statistically significant differences were found in the WeeFIM scores between type I and type II and between type IIIa and IIIb patients. However, no significant difference could be observed between type II and type IIIa SMA patients in the overall WeeFIM scores or performance in any of the 3 domains.Conclusion. We found that there was improvement in survival in SMA patients as compared with other studies. Assistance or supervision was needed for the majority of SMA patients for both mobility and self-care domains. With improvement in survival as a result of medical advances, assessment of the most current or the best-ever functional status at a designated age might be an important criterion for classification of SMA.