When a person's liver is not working properly, the risk of having a seizure goes way up. Millions of people with chronic liver problems, whether because of hepatitis B, alcoholism, or an inherited metabolic disorder, also contend with seizures.
Ammonia appears to be the point of connection between liver problems and seizures. Now researchers have found an unlikely, but promising new treatment: a drug normally used to treat high blood pressure.
Once inside the brain, ammonia works as an electrical trigger, keeping brain cells in a state of heightened excitability. This can lead to tremors and seizures.
When ammonia accumulates, these gatekeepers are kept on “overdrive,” allowing too many ions to flow into brain cells at once. This chemical imbalance leads to a spike in the electrical activity inside the cells and to the development of seizures.
People with malfunctioning livers cannot process ammonia, a common waste product of protein breakdown. As a result, ammonia builds up in the bloodstream as a gas and makes its way through the blood into brain tissue.
Once inside the brain, ammonia works as an electrical trigger, keeping brain cells in a state of heightened “excitability.” This can lead to tremors and seizures, which in the long-term can cause permanent neurological impairment.
Bumetanide or Bumex®, a drug normally used to treat high blood pressure, has shown some promise for patients with impaired livers and metabolic problems. The drug seems to reduce seizures by acting on the same biological pathways associated with chronic liver disease.
The results bode well for humans with metabolic disorders and liver impairments who also suffer from chronic seizures. Bumetanide is already an approved drug and is unlikely to cause any additional side effects in the brain.
“The fact that bumetanide is already approved for use gives us a tremendous head start in terms of developing a potential treatment for this condition,” lead author Maiken Nedergaard said in a statement.
This study is published in advance of print in the online version of Nature Medicine.