EEG-based biomarker for the identification of mild cognitive impairment via coherency analysis and iterative dynamic time warping.

Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disorder characterized by widespread eosinophilic intranuclear inclusions []. Most of the NIID patients are adults with insidious onset and distinctive white matter lesion (WML) patterns on MRI, such as diffusion-weighted imaging (DWI) hyperintensities at the corticomedullary junction (CMJ) and fluid-attenuated inversion recovery (FLAIR) hyperintensities in the paravermal region [–], while infantile and juvenile cases are also documented []. Since the discovery of GGC trinucleotide repeat expansions as a genetic cause of NIID in 2019 [–], increasing clinical recognition has revealed a broad phenotypic spectrum encompassing dementia, movement disorders, autonomic dysfunction, peripheral neuropathy, episodic neurological events, myopathy, and extra-nervous manifestations [, , –]. These findings have led to the propose of a concept of -related repeat expansion disorders []. Although account for the majority of adult-onset NIID, particularly in East Asian populations, genetically unresolved cases have been reported [], suggesting a genetic heterogeneity. Recently, a few studies, including our own, have reported a small number of -related NIID cases presenting with hydrocephalus-like presentations, characterized by marked ventriculomegaly accompanied by cognitive impairment, gait disturbance, and/or bladder dysfunction, closely mimicking idiopathic normal pressure hydrocephalus (iNPH) [–]. However, the prevalence, clinical profile, and pathological underpinnings of this new phenotype remain poorly delineated. Although two previously reported cases showed negative response to cerebrospinal fluid (CSF) tap-test [, ], systematic evaluation of the therapeutic value of CSF drainage or shunt procedures in NIID is lacking. Given the current absence of effective disease-modifying therapies for NIID, a clearer characterization of this potentially treatable phenotype is urgently needed. This retrospective observational study aims to explore the clinical, radiological, and pathological characteristics of -related NIID individuals with hydrocephalus-like presentations. In this study, ventriculomegaly refers to structural ventricular enlargement, whereas hydrocephalus-like phenotype denotes a clinical-radiological constellation resembling iNPH. These terms are not interchangeable. Our findings suggest that a hydrocephalus-like phenotype is frequent in NIID and exhibits features distinct from those patients without ventriculomegaly, which is prone to be misdiagnosed as iNPH due to a partial response to CSF drainage. This work extends the known clinical spectrum and highlights the potential therapeutic value of CSF shunt in this disease, adding to our knowledge of the involvement of CSF dynamics in genetic neurodegenerative disorders.