Researchers Explore Pharmacological Complement to iNPH Brain Shunt Procedures
An interdisciplinary team of researchers from the Miller School and Weill Cornell Medical College has found that a drug commonly given to young, obese females to treat idiopathic intracranial hypertension, a neurological disorder characterized by elevated pressure in the brain not caused by a tumor or other disease, also has a condition-reversing effect when given to seniors of either gender who have idiopathic normal-pressure hydrocephalus (iNPH), a type of brain malfunction caused by excessive accumulation of cerebrospinal fluid.
Their findings appeared in an article entitled “Low-dose acetazolamide reverses periventricular white matter hyperintensities in iNPH” in the April 15 issue of the journal Neurology, published by the American Academy of Neurology.
Noam Alperin, Ph.D., professor of radiology and biomedical engineering and Director of the Physiologic Imaging and Modeling Lab, was the article’s lead author, with Carlos Oliu, a third-year medical student, as co-first author. “A true radiology-neurology interdisciplinary collaboration” is how Alperin described the study.
“The excessive cerebrospinal fluid (CSF) in iNPH extends beyond the boundaries of the enlarged ventricles of the brain; it penetrates the adjacent white matter brain tissue and disturbs the normal functions of these brain regions,” said Alperin. “Common effects are unsteady walking, urinary incontinence and dementia, depending on the affected part of the brain.”
The conventional treatment for iNPH is to drain the fluid through a shunt surgically implanted in the brain. Alperin, after observing the success of treatments for idiopathic intracranial hypertension using a drug called acetazolamide, wondered if it might help iNPH patients, too. He met with Norman R. Relkin, M.D., Ph.D., associate professor of clinical neurology at Weill Cornell and a world-renowned expert in iNPH, and suggested that they collaborate in a study to test the idea.
Eight subjects were given an off-label low dose of acetazolamide. In five of the subjects, the symptoms were reversed. Of the remaining three, one had no further progression, and the other two were nonresponsive to both pharmacologic and conventional shunt treatments.
“Advanced quantitative neuroimaging allowed us to demonstrate, for the first time, changes in the periventricular white matter brain regions following pharmacologic treatment,” said Alperin. “We were able to measure the retreat of the CSF from the white matter regions surrounding the brain ventricles.”
There are challenges with the drug used in the study, Alperin said. First, acetazolamide is not approved as a treatment for iNPH, so the study was conducted using it off-label. Second, it is not an easy drug for seniors to tolerate, and side effects involve electrolyte imbalance. However, the study still suggests that pharmacological treatment is feasible in iNPH.
“NIH wants a non-surgical treatment for iNPH, because shunt treatment is associated with a high failure rate,” said Alperin. “Our next step, therefore, is to create a dedicated clinic focused on developing a pharmacological treatment that complements the surgical treatment for iNPH and other gait-related disorders.”
To develop the clinic, Alperin will work with a team of clinicians and researchers from the Miller School, including David J. Adams, M.D., professor of neurology; Roberto C. Heros, M.D., professor and Co-Chair of Neurological Surgery; Corneliu Luca, M.D., Ph.D., assistant professor of neurology; and Ralph L. Sacco, M.D., M.S., professor and Olemberg Chair of Neurology.
“Because iNPH is more prevalent in people over 60, we have a large potential patient population here in South Florida,” said Alperin. “We would also like to expand our research collaboration to include other locations.”