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巴基斯坦卡拉奇三级医院原发性脑肿瘤患儿和青少年神经认知结局的预测因素:一项前瞻性队列研究。

Predictors of neurocognition outcomes in children and young people with primary brain tumor presenting to tertiary care hospitals of Karachi, Pakistan: a prospective cohort study.

机构信息

Department of Surgery, Aga Khan University, Karachi, Pakistan.

Global Health and Migration Unit, Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.

出版信息

Childs Nerv Syst. 2024 Jun;40(6):1707-1719. doi: 10.1007/s00381-024-06306-x. Epub 2024 Feb 16.

Abstract

INTRODUCTION

Primary brain tumors are a common cause of morbidity and mortality in children and young people (CYP) globally. Impaired neurocognitive function is a potential severe consequence in primary brain tumor (PBT) survivors. There are no in-depth studies from low- and middle-income countries (LMICs) to inform management and follow-up. The research questions of this study were as follows: Are the sociodemographic factors (lower age of CYP, female gender, low socioeconomic status, low parental education), disease-related factors (high grade of tumor, presence of seizures, presence of hydrocephalous), and treatment-related factors (adjuvant therapy, no surgical intervention, post-treatment seizures, placement of shunts) associated with decline in neurcognition outcomes 12 months post-treatment in CYP with PBTs?

METHODS

A prospective cohort study was conducted from November 2020 to July 2023 at the Aga Khan University Hospital and Jinnah Postgraduate Medical Centre, tertiary care hospitals in Karachi, Pakistan. All CYP aged 5 to 21 years with a newly diagnosed PBTs were eligible. The neurocognition assessment was undertaken by a psychologist at two points, i.e., pre-treatment and at 12 months post-treatment using validated tools. The verbal intelligence was assessed by Slosson Intelligence tool, revised 3rd edition (SIT-R3), perceptual reasoning by Raven's Progressive Matrices (RPM), and the Processing Speed Index by Wechsler Intelligence Scale (WISC V) and Wechsler Adult Intelligence Scale (WAIS-IV). The data were analyzed by STATA version 12 software. Generalized estimating equation (GEE) was used to determine the factors associated with the mean change in 12 months post-treatment verbal and non-verbal neurocognition scores. Unadjusted and adjusted beta coefficients with their 95% confidence intervals were reported.

RESULTS

A total of 48 CYPs with PBTs were enrolled, 23 (48%) of them were lost to follow-up and 10 (21%) died. The remaining 25 (52%) were reassessed 12 months after treatment. On multivariable analysis, a significant decline in verbal intelligence scores at 12 months was predicted by post-treatment seizures beta =  - 20.8 (95% CI, - 38.2, - 3.4), mothers having no formal educational status and lower household monthly income. Similarly, a significant decline in perceptual reasoning scores was also predicted by post-treatment seizures beta =  - 10.7 (95% CI, - 20.6, - 0.8), mothers having no formal education and having lower household monthly income. Worsening of processing speed scores at 12 months post-treatment were predicted by tumor histology, post-treatment seizures beta =  - 33.9 (95% CI, - 47.7, - 20.0), lower educational status of the mother, and having lower household monthly. However, an improvement was seen in processing speed scores after surgical tumor resection.

CONCLUSION

In this novel study, the post-treatment mean change in verbal and non-verbal neurocognition scores was associated with sociodemographic, tumor, and treatment factors. These findings may have potential implications for targeted early psychological screening of higher risk CYP with PBTs. Identification of these predictors may serve as a foundation for developing more cost-effective treatment thereby alleviating the burden of neurocognitive morbidity. However to establish generalizability, future research should prioritize larger-scale, multicountry studies. (Trial registration: ClinicalTrials.gov Identifier: NCT05709522).

摘要

简介

原发性脑肿瘤是全球儿童和青少年(CYP)发病率和死亡率的一个常见原因。在原发性脑肿瘤(PBT)幸存者中,神经认知功能受损是一个潜在的严重后果。来自中低收入国家(LMICs)的深入研究还没有为管理和随访提供信息。本研究的研究问题如下:社会人口因素(CYP 年龄较小、女性、社会经济地位较低、父母教育程度较低)、疾病相关因素(肿瘤级别较高、存在癫痫发作、存在脑积水)和治疗相关因素(辅助治疗、无手术干预、治疗后癫痫发作、放置分流器)是否与 PBT 后 12 个月的神经认知结果下降有关?

方法

这是一项前瞻性队列研究,于 2020 年 11 月至 2023 年 7 月在巴基斯坦卡拉奇的 Aga Khan 大学医院和 Jinnah 研究生医学中心进行。所有新诊断为 PBT 的年龄在 5 至 21 岁的 CYP 均符合条件。神经认知评估由心理学家在两个时间点进行,即治疗前和治疗后 12 个月,使用经过验证的工具。言语智力通过 Slosson 智力工具(修订版 3 版)进行评估,知觉推理通过 Raven 的渐进矩阵(RPM)进行评估,处理速度指数通过韦氏智力量表(WISC V)和韦氏成人智力量表(WAIS-IV)进行评估。数据由 STATA 版本 12 软件进行分析。广义估计方程(GEE)用于确定与治疗后 12 个月言语和非言语神经认知评分平均变化相关的因素。报告了未经调整和调整后的 beta 系数及其 95%置信区间。

结果

共有 48 名患有 PBT 的 CYP 被纳入研究,其中 23 名(48%)失访,10 名(21%)死亡。其余 25 名(52%)在治疗后 12 个月进行了重新评估。多变量分析显示,治疗后癫痫发作与言语智力评分在 12 个月时显著下降有关,β= -20.8(95%CI,-38.2,-3.4),母亲没有正规教育背景和较低的家庭月收入。同样,治疗后癫痫发作也与知觉推理评分显著下降有关,β= -10.7(95%CI,-20.6,-0.8),母亲没有正规教育背景和较低的家庭月收入。治疗后 12 个月处理速度评分恶化与肿瘤组织学、治疗后癫痫发作有关,β= -33.9(95%CI,-47.7,-20.0),母亲教育程度较低,家庭月收入较低。然而,手术切除肿瘤后处理速度评分有所提高。

结论

在这项新的研究中,治疗后言语和非言语神经认知评分的平均变化与社会人口、肿瘤和治疗因素有关。这些发现可能对具有 PBT 的高风险 CYP 的有针对性的早期心理筛查具有潜在意义。识别这些预测因素可能为制定更具成本效益的治疗方法奠定基础,从而减轻神经认知发病率的负担。然而,为了建立普遍性,未来的研究应优先进行更大规模、多国的研究。(试验注册:ClinicalTrials.gov 标识符:NCT05709522)

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a75/11111568/1ed5c094fb1c/381_2024_6306_Fig1_HTML.jpg

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