Background

Pyridoxine monotherapy in PDE-ALDH7A1 often results in adequate seizure control, but neurodevelopmental outcome varies. Detailed long-term neurological outcome is unknown. Here we present the cognitive and neurological features of the Dutch PDE-ALDH7A1 cohort.

Methods

Neurological outcome was assessed in 24 patients (age 1–26 years); classified as normal, complex minor neurological dysfunction (complex MND) or abnormal. Intelligence quotient (IQ) was derived from standardized IQ tests with five severity levels of intellectual disability (ID). MRI's and treatments were assessed.

Results

Ten patients (42%) showed unremarkable neurological examination, 11 (46%) complex MND, and 3 (12%) cerebral palsy (CP). Minor coordination problems were identified in 17 (71%), fine motor disability in 11 (46%), posture/muscle tone deviancies in 11 (46%) and abnormal reflexes in 8 (33%). Six patients (25%) had an IQ > 85, 7 (29%) borderline, 7 (29%) mild, 3 (13%) moderate, and 1 severe ID. Cerebral ventriculomegaly on MRI was progressive in 11. Three patients showed normal neurologic exam, IQ, and MRI. Eleven patients were treated with pyridoxine only and 13 by additional lysine reduction therapy (LRT). LRT started at age <3 years demonstrated beneficial effect on IQ results in 3 patients.

Discussion

Complex MND and CP occurred more frequently in PDE-ALDH7A1 (46% and 12%) than in general population (7% and 0.2%, Peters et al., 2011, Schaefer et al., 2008). Twenty-five percent had a normal IQ. Although LRT shows potential to improve outcomes, data are heterogeneous in small patient numbers. More research with longer follow-up via the International PDE Registry (www.pdeonline.org) is needed.

中文翻译：

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荷兰吡哆醇依赖性癫痫 (PDE-ALDH7A1) 队列患者的认知和神经学结果，一项横断面研究

背景

PDE-ALDH7A1 中的吡哆醇单药治疗通常会导致充分的癫痫发作控制，但神经发育结果各不相同。详细的长期神经学结果尚不清楚。在这里，我们介绍了荷兰 PDE-ALDH7A1 队列的认知和神经学特征。

方法

评估了 24 名患者（1-26 岁）的神经学结果；分为正常、复杂的轻微神经功能障碍（复杂的 MND）或异常。智商 (IQ) 来自具有五个严重程度的智力障碍 (ID) 的标准化 IQ 测试。对 MRI 和治疗进行了评估。

结果

10 名患者 (42%) 神经系统检查无异常，11 名 (46%) 复杂 MND 和 3 名 (12%) 脑瘫 (CP)。17 人 (71%) 出现轻微协调问题，11 人 (46%) 出现精细运动障碍，11 人 (46%) 出现姿势/肌肉张力异常，8 人 (33%) 出现异常反射。6 名患者 (25%) 的智商 > 85，7 名 (29%) 处于临界状态，7 名 (29%) 轻度，3 名 (13%) 中度和 1 名重度 ID。11 例 MRI 显示的脑室扩大呈进行性。3 例患者神经系统检查、智商和 MRI 均正常。11 名患者仅接受吡哆醇治疗，13 名患者接受额外的赖氨酸减少疗法 (LRT)。3 岁以下开始 LRT 证明对 3 名患者的 IQ 结果有益。

讨论

复杂 MND 和 CP 在 PDE-ALDH7A1（46% 和 12%）中的发生频率高于一般人群（7% 和 0.2%，Peters 等，2011，Schaefer 等，2008）。25% 的人智商正常。尽管 LRT 显示出改善结果的潜力，但数据在小患者数中存在异质性。需要通过国际 PDE 登记处 (www.pdeonline.org) 进行更多研究和更长时间的随访。