Cerebrospinal fluid transcripts may predict shunt surgery responses in normal pressure hydrocephalus.
Zachary LevinOwen P LearyVictor MoraShawn KantSarah BrownKonstantina SvokosUmer AkbarThomas SerrePetra KlingeAlexander FleischmannMaria Grazia RuoccoPublished in: Brain : a journal of neurology (2023)
Molecular biomarkers for neurodegenerative diseases are critical for advancing diagnosis and therapy. Normal pressure hydrocephalus (NPH) is a neurological disorder characterized by progressive neurodegeneration, gait impairment, urinary incontinence and cognitive decline. In contrast to most other neurodegenerative disorders, NPH symptoms can be improved by the placement of a ventricular shunt that drains excess CSF. A major challenge in NPH management is the identification of patients who benefit from shunt surgery. Here, we perform genome-wide RNA sequencing of extracellular vesicles in CSF of 42 NPH patients, and we identify genes and pathways whose expression levels correlate with gait, urinary or cognitive symptom improvement after shunt surgery. We describe a machine learning algorithm trained on these gene expression profiles to predict shunt surgery response with high accuracy. The transcriptomic signatures we identified may have important implications for improving NPH diagnosis and treatment and for understanding disease aetiology.
Keyphrases
- genome wide
- minimally invasive
- cerebrospinal fluid
- coronary artery bypass
- cognitive decline
- machine learning
- pulmonary artery
- dna methylation
- urinary incontinence
- end stage renal disease
- surgical site infection
- chronic kidney disease
- mild cognitive impairment
- multiple sclerosis
- single cell
- heart failure
- gene expression
- percutaneous coronary intervention
- peritoneal dialysis
- copy number
- stem cells
- newly diagnosed
- coronary artery
- prognostic factors
- magnetic resonance
- artificial intelligence
- subarachnoid hemorrhage
- acute coronary syndrome
- left ventricular
- pulmonary hypertension
- contrast enhanced
- coronary artery disease
- replacement therapy
- mesenchymal stem cells
- physical activity