Familial vs sporadic normal pressure hydrocephalus: a comparative study

Area of Science:

• Neurology
• Genetics

Background:

• Normal pressure hydrocephalus (NPH) is a syndrome characterized by gait impairment, urinary incontinence, and cognitive decline due to cerebrospinal fluid buildup.
• NPH can be secondary, idiopathic, or familial, with distinct clinical and genetic profiles.

Purpose of the Study:

• To compare sporadic and familial NPH cases in clinical, radiological, and surgical response aspects.
• To identify novel genetic mutations associated with familial NPH.

Main Methods:

• Retrospective analysis of 139 patients evaluated for NPH, including 95 diagnosed with idiopathic NPH (iNPH).
• Collection of clinical, radiological, and gait data; assessment of familial history and inheritance patterns.
• Whole exome sequencing to identify genetic variants in familial NPH cases.

Main Results:

• Familial NPH was identified in 9.5% of cases and showed comparable demographics to sporadic NPH.
• Familial cases exhibited significantly better cognitive scores and a higher incidence of upper-limb action tremor.
• No significant differences in radiological markers were observed; both groups responded well to ventriculoperitoneal shunting (VPS).
• A novel pathogenic NEIL1 variant was identified in twin patients with familial NPH.

Conclusions:

• Familial NPH represents a significant subset of iNPH, presenting with distinct cognitive and tremor characteristics.
• The genetic basis of familial NPH is heterogeneous, with NEIL1 emerging as a potential associated gene.