Normal Pressure Hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder of aging that is characterized by enlarged cerebral ventricles, gait difficulty, incontinence and dementia. It is a common disorder that occurs almost exclusively after the age of 60. About 1.3% of patients over the age of 65 and 9-14% of nursing home residents are thought to have iNPH. Unfortunately, more than 90% of these patients remain misdiagnosed or undiagnosed, in part because the symptoms of iNPH resemble the symptoms of other neurodegenerative diseases, and in part because many health care practitioners are unfamiliar with this disorder. The etiology of iNPH is not known. Scattered reports of familial cases of iNPH suggest a genetic origin, but the genes involved are unknown. To investigate this matter, we have used exome sequencing to look for genetic factors associated with iNPH. We find recurrent heterozygous mutations in 10 genes, nearly all of which show increased expression in the ciliated ventricular epithelium and/or choroid plexus. Many have previously been associated with the function of cilia. ]]>
Patients who presented to a neurosurgical clinic with unexplained complaints of ventricular enlargement, gait difficulty, incontinence and/or dementia underwent an evaluation that included a history, neurological examination and cranial imaging. Patients were consented for the study prior to CSF drainage.  A trial of lumbar CSF drainage was then performed. Quantitative measurements of gait speed, stride length and performance on the Timed Up and Go (TUG) test, as well as patient and caregiver reports of changes in urinary incontinence, were used to assess symptoms before and after CSF drainage as we have described previously (Yang, Hickman et al., 2016). Only those patients who improved after a trial of CSF drainage and subsequent ventriculoperitoneal shunt placement were included for whole exome analysis.]]>