Katharine Hepburn's shaky hands and voice resemble the tremor associated with Parkinson's disease but stem from an even more common movement disorderessential tremor.
Though it's up to 20 times more common than Parkinson's, essential tremor is more mysterious. No cellular defect has been linked to the disease, which affects up to 6 percent of the population, and its environmental and genetic roots remain obscure.
New research from Dr. Elan D. Louis, assistant professor of neurology, and his colleagues may lead to answers on both fronts. They recently identified a brain region where cells may be dying in tremor patients and an environmental toxin that may trigger the disease. The research was published in the Nov. 15 Neuroscience Letters and the Dec. 24 Neurology.
Though essential tremor sometimes becomes so disabling that patients are unable to work or feed themselves, the disease does not shorten the patient's life and is less studied than other neurological diseases. Only 15 postmortem brains of essential tremor patients have been examined in the last 100 years.
Some of these postmortem exams suggested that cells in the cerebellar cortexthe "little brain" near the brainstem that helps control movementshrink or disappear in people with the disease.
To get a better picture of possible cellular deterioration, Dr. Louis and Dr. Dikoma Shungu, associate professor of clinical radiology (physics), used a relatively new brain scanning technique to look for signs of degeneration in living patients. The method, proton magnetic resonance spectroscopic imaging, or MRSI, measures the concentration of chemicals inside neurons, giving researchers a more detailed view of cell activity than that provided by other types of brain imaging. Dr. Louis looked primarily at the level of N-acetyl-aspartate (NAA) in the brain because a low level is believed to indicate damaged or dying neurons.
The researchers measured the amount of NAA in the brains of 16 essential tremor patients and nine controls of similar age. As reported in the Neuroscience Letters paper, the average level of NAA (expressed as the ratio of NAA to creatine) was 20 percent lower in the cerebellar cortex of essential tremor patients than in controls. No other regions showed signs of degeneration. The group also found that the lower the NAA levels, the more severe the tremor, suggesting that degeneration is related to the tremor.
Dr. Louis has funding from the International Essential Tremor Foundation to look at brain tissue from deceased patients so the types of cells affected and the chemicals changes they undergo can be more precisely identified.
Other research by Dr. Louis and his colleagues has started to identify possible environmental triggers that may spur neurodegeneration in essential tremor. One such environmental agent may be the beta-carboline alkaloids found in common plant-derived foods, such as wheat and rice, but which also are produced in the body. Injections of large doses of alkaloids damage cerebellar neurons and induce tremor in animal models of the disease.
In the study published in Neurology of 100 essential tremor patients and 100 controls, Dr. Louis, in collaboration with Dr. Wei Zheng, associate professor of clinical public health (in environmental health sciences) (in pharmacology) in the Mailman School of Public Health, found that the level of one of the alkaloidsharmanewas two times higher in the blood of patients than the controls, though far lower than the doses used in animal models. Dr. Louis says patients may be chronically exposed to higher harmane levels from their diet, metabolize the alkaloid differently, or simply make more of it.
"We are now on the verge of isolating genes and environmental factors associated with essential tremor and finding actual changes in the brain," Dr. Louis says. "This will allow us, eventually, to devise more effective therapies. Ultimately, we want to stop the disease either by reducing toxin intake or by devising neuroprotective strategies."
Dr. Louis' research was supported by the National Institutes of Health, the American Federation for Aging Research, the Charles A. Dana Foundation, and the International Essential Tremor Foundation.