Clinical and radiographic course of arrested cerebral adrenoleukodystrophy

Objective: To gain insight into the natural history of arrested cerebral adrenoleukodystrophy (CALD), we quantified the change in Neurologic Function Score (NFS) and Loes Score (LS) over time in patients whose cerebral lesions spontaneously stopped progressing.

Methods: We retrospectively reviewed a series of 22 patients with arrested CALD followed longitudinally over a median time of 2.4 years (0.7 – 17.0). Primary outcomes were change in radiographic disease burden (measured by LS) and clinical symptoms (measured by NFS) between patients who never developed a contrast-enhancing lesion (GdE- subgroup), and those who did (GdE+ subgroup). Secondary analyses comparing patterns of neuroanatomical involvement and lesion number, and prevalence estimates, were performed.

Results: Cerebral lesions were first detected at a median age of 23.3 years old (8.0 – 67.6), with an initial LS of 4 (0.5 – 9).  NFS was 0.5 (0 – 6). Overall change in NFS or LS per year did not differ between subgroups. No patients who remained GdE- converted to a progressive CALD phenotype. The presence of contrast enhancement was associated with disease progression (rs = 0.559, p < 0.001). Four patients (18.2%) underwent step-wise progression, followed by spontaneous resolution of contrast enhancement, and re-arrest of disease.  Three patients (13.6%) converted to progressive CALD.  Nineteen patients (86.4%) have arrested CALD at most recent follow-up. The prevalence of arrested CALD is 12.4%.

Conclusion: Arrested CALD lesions can begin in childhood, and patients are often asymptomatic early in disease. The majority of patients remain stable.  However, clinical and MRI surveillance is recommended as a minority of patients undergo step-wise progression, or conversion to progressive CALD.

研究目的：为深入探究静止型脑型肾上腺脑白质营养不良（cerebral adrenoleukodystrophy, CALD）的自然病程，我们对脑部病变自发停止进展的患者，量化其神经功能评分（Neurologic Function Score, NFS）与Loes评分（Loes Score, LS）随时间的变化情况。

研究方法：我们对22例经纵向随访确诊的静止型脑型肾上腺脑白质营养不良患者开展回顾性分析，中位随访时长为2.4年（范围0.7~17.0年）。本研究的主要结局指标为：对比从未出现钆增强（gadolinium-enhancing, GdE）病灶的GdE-亚组与出现钆增强病灶的GdE+亚组患者，其影像学疾病负荷（以Loes评分衡量）与临床症状（以神经功能评分衡量）的变化差异。此外还开展了次要分析，对比两组的神经解剖受累模式、病灶数量，并进行患病率估算。

研究结果：患者首次被检出脑部病变时的中位年龄为23.3岁（范围8.0~67.6岁），初始Loes评分为4分（范围0.5~9分），初始神经功能评分为0.5分（范围0~6分）。两组患者每年的神经功能评分或Loes评分总体变化无显著差异。未出现钆增强病灶的GdE-亚组患者均未进展为进展性脑型肾上腺脑白质营养不良表型。钆增强病灶的存在与疾病进展呈显著正相关（斯皮尔曼相关系数rs=0.559，P<0.001）。共有4例患者（占比18.2%）先后出现阶梯式疾病进展，随后自发出现钆增强病灶消退，病变再次进入静止状态。3例患者（占比13.6%）进展为进展性脑型肾上腺脑白质营养不良。截至最近一次随访，19例患者（占比86.4%）仍维持静止型CALD状态。静止型脑型肾上腺脑白质营养不良的患病率为12.4%。

研究结论：静止型脑型肾上腺脑白质营养不良的病变可始于儿童时期，患者在疾病早期通常无明显症状。大部分患者病情可维持稳定，但鉴于少数患者会出现阶梯式疾病进展或进展为进展性脑型肾上腺脑白质营养不良，因此推荐对该类患者进行临床与MRI随访监测。