Decreased Expression of hsa-miR-4274 in Cerebrospinal Fluid of Normal Pressure Hydrocephalus Mimics with Parkinsonian Syndromes

帕金森病综合征正常压力脑积水患者脑脊液中 hsa-miR-4274 表达降低

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作者:Ivana Jurjević, Masakazu Miyajima, Ikuko Ogino, Chihiro Akiba, Madoka Nakajima, Akihide Kondo, Mika Kikkawa, Mitsuyasu Kanai, Nobutaka Hattori, Hajime Arai

Background

Patients presenting with the classical idiopathic normal pressure hydrocephalus (iNPH) triad often show additional parkinsonian spectrum signs. Accurate differential diagnosis strongly influences the long-term outcome of cerebrospinal fluid (CSF) shunting.

Conclusion

Levels of CSF hsa-miR-4274 can differentiate PS from patients with iNPH, AD, and NC. This may be clinically useful for diagnostic purposes and predicting shunt treatment responses.

Methods

Two cohorts of 81 patients (cohort 1, n = 55; cohort 2, n = 26) with possible iNPH who were treated in two centers between January 2011 and May 2014 were studied. In both cohorts, CSF samples were obtained from patients clinically diagnosed with iNPH (n = 21 and n = 10, respectively), possible iNPH with parkinsonian spectrum (PS) (n = 18, n = 10, respectively), possible iNPH with Alzheimer's disease (AD) (n = 16), and non-affected elderly individuals (NC) (n = 6). A three-step qRT-PCR analysis of the CSF samples was performed to detect miRNAs that were differentially expressed in the groups.

Objective

The aim of this study was to find potential CSF microRNA (miRNA) biomarkers for NPH mimics with parkinsonian syndromes that can reliably distinguish them from iNPH patients.

Results

The expression of hsa-miR-4274 in CSF was decreased in both cohorts of PS group patients (cohort 1: p < 0.0001, cohort 2: p < 0.0001), and was able to distinguish PS from iNPH with high accuracy (area under the curve = 0.908). The CSF concentration of hsa-miR-4274 also correlated with the specific binding ratio of ioflupane (123I) dopamine transporter scan (r = -0.494, p = 0.044). By contrast, the level of hsa-miR-4274 was significantly increased in the PS group after CSF diversion.

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