Mitchell James L, Lyons Hannah S, Walker Jessica K, Yiangou Andreas, Thaller Mark, Grech Olivia, Alimajstorovic Zerin, Tsermoulas Georgios, Brock Kristian, Mollan Susan P, Sinclair Alexandra J
Translational Brain Science, Department of Metabolism and Systems Science, College of Medicine and Health, University of Birmingham, Birmingham, UK.
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK.
Headache. 2025 Feb;65(2):258-268. doi: 10.1111/head.14897. Epub 2025 Jan 24.
To gain initial insight into the efficacy to lower intracranial pressure (ICP), side effects, and effects on cognition of five drugs commonly used to treat idiopathic intracranial hypertension (IIH).
Limited clinical data exist for the treatment for IIH. Impaired cognition is recognized in IIH and can be exacerbated by medications.
This human experimental medicine study was a secondary analysis that focused on an unblinded randomized, sequential, cross-over extension of a previously completed randomized controlled trial. This study evaluated females with active IIH, recruited from University Hospital Birmingham, UK. Participants were treated, in randomized order, for 2 weeks with acetazolamide, amiloride, furosemide, spironolactone, and topiramate; assessment was at baseline and 2 weeks with a minimum 1-week drug washout between drugs. The primary outcome was change in ICP at 2 weeks post-drug administration. The cognitive evaluation was an exploratory study of the trial. ICP was recorded with telemetric, intraparenchymal ICP monitors (Raumedic, Hembrechts, Germany). Adverse events were recorded, and cognition was assessed utilizing the National Institutes of Health Toolbox Cognitive Battery.
Fourteen participants were recruited and evaluated by intention-to-treat analysis. Mean (standard deviation) body mass index was 37.3 (7.0) kg/m and ICP was 33.2 (7.1) cm cerebrospinal fluid (CSF) at baseline. ICP fell with four drugs (mean [standard error (SE)]), acetazolamide -3.3 (1.0) mmHg, p = 0.001, furosemide -3.0 (0.9) mmHg, p = 0.001, spironolactone -2.7 (0.9) mmHg, p = 0.003, and topiramate -2.3 (0.9) mmHg, p = 0.010. There was no significant difference between drugs. Side effects were common with acetazolamide (100%, 11/11) and topiramate (93%, 13/14). Baseline cognitive performance was impaired, T-score (mean [SE]) 37.2 (2.6). After treatment, there was a further significant reduction in the fluid cognition domain (ability to process and integrate) with acetazolamide (mean T-score [SE]), -5.0 (2.6), p = 0.057 and topiramate -4.1 (2.0), p = 0.061.
Acetazolamide, furosemide, spironolactone, and topiramate marginally reduced ICP. While their effects were not significant, this study was not powered to detect a difference between drugs. Participants reported significant side effects with acetazolamide and topiramate including cognitive decline. Cognitive measures were impaired by acetazolamide and topiramate. Therapeutics with greater efficacy and a favorable side effect profile are an unmet need in the treatment of IIH.
初步了解常用于治疗特发性颅内高压（IIH）的五种药物降低颅内压（ICP）的疗效、副作用及对认知的影响。
关于IIH治疗的临床数据有限。IIH患者存在认知功能受损，且药物可能会使其加重。
这项人体实验医学研究是一项二次分析，重点关注先前完成的随机对照试验的非盲随机、序贯、交叉扩展研究。该研究评估了从英国伯明翰大学医院招募的活动性IIH女性患者。参与者按随机顺序接受乙酰唑胺、阿米洛利、呋塞米、螺内酯和托吡酯治疗2周；在基线和2周时进行评估，药物之间至少有1周的洗脱期。主要结局是给药后2周时ICP的变化。认知评估是该试验的一项探索性研究。使用遥测式脑实质内ICP监测仪（德国黑姆布雷希茨的 Raumedic公司生产）记录ICP。记录不良事件，并使用美国国立卫生研究院工具箱认知电池评估认知情况。
共招募了14名参与者，并按意向性分析进行评估。基线时，平均（标准差）体重指数为37.3（7.0）kg/m²，ICP为33.2（7.1）cm脑脊液（CSF）。四种药物可使ICP降低（平均值[标准误（SE）]），乙酰唑胺降低-3.3（1.0）mmHg，p = 0.001；呋塞米降低-3.0（0.9）mmHg，p = 0.001；螺内酯降低-2.7（0.9）mmHg，p = 0.003；托吡酯降低-2.3（0.9）mmHg，p = 0.010。各药物之间无显著差异。乙酰唑胺（100%，11/11）和托吡酯（93%，13/14）的副作用常见。基线认知表现受损，T分数（平均值[SE]）为37.2（2.6）。治疗后，乙酰唑胺（平均值T分数[SE]）使流体认知领域（处理和整合能力）进一步显著降低，降低了-5.0（2.6），p = 0.057；托吡酯降低了-4.1（2.0），p = 0.061。
乙酰唑胺、呋塞米、螺内酯和托吡酯可使ICP略有降低。虽然它们的效果不显著，但本研究的样本量不足以检测出药物之间的差异。参与者报告乙酰唑胺和托吡酯有显著副作用，包括认知下降。乙酰唑胺和托吡酯损害了认知指标。在IIH治疗中，仍需要疗效更好且副作用较小的治疗方法。
