Joung Joshua Y, Gallison Kathryn J, Liu Geraldine W, Berger Jessica A, Drum Elizabeth T, Dubow Scott R, McClung Heather A, Faig Walter, Avery Robert A, Liu Grant T, Narula Sona, Vossough Arastoo, Waldman Amy T
Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Pediatr Neurol. 2025 Jul;168:105-111. doi: 10.1016/j.pediatrneurol.2025.04.016. Epub 2025 May 8.
Alexander disease (AxD) is caused by a gain-of-function mutation in GFAP resulting in the formation of Rosenthal fibers, which are hypothesized to impair cerebrospinal fluid circulation, potentially resulting in increased ICP. We explored the prevalence of elevated intracranial pressure (ICP) in AxD.
Patients with AxD underwent a neurological examination, lumbar puncture (LP) with opening pressure (OP) with legs flexed, and brain magnetic resonance imaging (MRI). Elevated OP was defined as >28 cm HO. A neuroradiologist (masked to clinical data and OP) reviewed MRIs for imaging signs of elevated ICP (flattened posterior sclerae, enlarged optic nerve sheaths, partially empty sella, and dural sinus venous stenoses). Descriptive statistics included proportions of patients with elevated OP and MRI findings. Mixed effects logistic regression was used to explore associations with elevated OP.
Sixty-nine LPs were performed in 43 patients; 21 (49%) patients had an elevated OP on at least one LP. Papilledema was not present among those with a concurrent undilated funduscopic examination. Although most patients were asymptomatic, two patients received acetazolamide for headache and vomiting with symptom benefit and reduced OP. There was no association between age and OP (P = 0.11). MRI features of increased ICP were primarily observed in those with elevated OP.
Elevated OP with legs flexed and MRI features of increased ICP occur frequently in AxD, even in the absence of overt clinical signs. The implications of increased ICP on patient outcomes and whether asymptomatic elevated OP requires treatment need to be determined in AxD.
亚历山大病（AxD）由胶质纤维酸性蛋白（GFAP）的功能获得性突变引起，导致罗森塔尔纤维形成，据推测这会损害脑脊液循环，可能导致颅内压（ICP）升高。我们探讨了AxD患者颅内压升高的患病率。
AxD患者接受了神经系统检查、双腿屈曲时测量初压（OP）的腰椎穿刺（LP）以及脑部磁共振成像（MRI）。OP升高定义为>28 cm H₂O。一名神经放射科医生（对临床数据和OP结果不知情）对MRI进行评估，以寻找ICP升高的影像学征象（后巩膜扁平、视神经鞘增粗、蝶鞍部分空泡化和硬脑膜窦静脉狭窄）。描述性统计包括OP升高患者的比例和MRI检查结果。采用混合效应逻辑回归分析来探讨与OP升高的相关性。
43例患者共进行了69次LP；21例（49%）患者至少有一次LP的OP升高。同时进行的眼底检查未发现视乳头水肿。虽然大多数患者无症状，但有两名患者因头痛和呕吐接受了乙酰唑胺治疗，症状得到缓解，OP降低。年龄与OP之间无相关性（P = 0.11）。ICP升高的MRI特征主要见于OP升高的患者。
AxD患者经常出现双腿屈曲时OP升高以及ICP升高的MRI特征，即使没有明显的临床体征。AxD中ICP升高对患者预后的影响以及无症状性OP升高是否需要治疗尚待确定。
