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Widespread Risk for Falls Attributed to Impaired Vestibular Function and Valproate


doi: 10.1097/01.NT.0000359049.07362.15
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A wider population than previously suspected may be at risk for falls as revealed by a small study of valproate in psychiatric inpatients and a large health survey that found impaired vestibular function through balance testing.

New data on the increased risk for falls among middle-aged adults and older — attributed to vestibular dysfunction in one study, and use of valproate in another — support the need for including gait testing in the regular neurological exam.



In a May 25 paper published in the online edition of the Archives of Internal Medicine, investigators at Johns Hopkins University reported that one-third of Americans over age 40 have impaired vestibular function revealed by balance testing, and may be at risk of falls.

Yuri Agrawal, MD, a resident in the department of otolaryngology at Johns Hopkins University School of Medicine, who led the study, said: “We want to get our message out” that not just the elderly are at risk of falling, and that the risk may not be obvious. Investigators found, for example, that many subjects were not aware of their vestibular dysfunction and problems with balance.

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The results were based on an analysis of data from a nationally representative sample of 5,086 adults ages 40 and older participating in the 2001–2004 National Health and Nutrition Examination Surveys (NHANES) — a younger and larger population than previously studied.

Those surveyed had been tested for balance with the modified Romberg Test of Standing Balance, which assesses the ability to stand by progressively restricting access to postural cues, and without using the arms for balance, pressure from the soles of the feet, and visual input. The test has subjects stand, feet together, on a firm surface without moving for 15 seconds, with eyes open and then eyes shut; then stand for 30 seconds on a compliant surface (foam pad), with eyes open and then eyes shut. A video link demonstrating the test is available at

Among findings, 80-year-olds and older had a 23-fold increased risk of falling compared with people in their 40s. Loss of vestibular abilities with age may explain much of this difference, the investigators noted in their report.

People who had symptoms of vestibular dysfunction, including dizziness — 26.8 percent — had 12 times the odds of falling. Asymptomatic subjects who failed the balance tests had a six-fold increased risk of falling.

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Risk for falls was associated with valproate use in a study described in San Francisco in May at the annual meeting of the American Psychiatric Association. Investigators reported that one-third of 488 psychiatric patients — average age, 47 years — who were hospitalized during a three-month period in 2008 fell while taking valproate. The rates of falls for valproate users were a 22.8 percent compared with 16.8 percent for non-users (p < 0.03).



Valproate is known to raise serum ammonia levels in instances of toxicity, said one of the investigators, Milton Luria, MD, medical director at the Greystone Park Psychiatric Institute in Morris Plains, NJ. Although valproate users did show elevated ammonia levels, there were no differences in levels among those that fell and those that did not.

“Our patients using valproate fall more often. We don't know why,” Dr. Luria said. A third of this inpatient population have metabolic syndrome, and a third are diabetic, Dr. Luria noted.

The NHANES analysis also suggests critical populations at risk. Diabetics were 70 percent more likely to suffer from vestibular impairment, likely from damage to the hair cells and small blood vessels in the inner ear. Those reporting a history of high blood pressure also had borderline significant increased risk of falling.

“I think part of the issue with diabetes, which is compounding, is they tend to lose their sensory perception,” said Dr. Agrawal. “The sum is probably greater than its parts to contribute to the risk of falling for diabetics.”

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David Thurman, MD, at the CDC National Center for Chronic Disease Prevention and Health Promotion, who co-authored the AAN practice parameter on falls published Feb. 5, 2008, in Neurology, noted that the increased risk of falls in the valproate study was not overwhelming, less than two fold. [For the Neurology Today story about the AAN guidelines, see “AAN Practice Guidelines: Neurologists Can Take Simple Steps to Reduce Fall injuries,” (Feb. 7, 2008)]

“Patients on higher doses of drugs with sedating side effects need to be watched more closely for risk of falls, and the risks are additive,” Dr. Thurman said, adding that this is consistent with the guidance given by the practice parameter. He pointed out that with some kinds of epilepsy, the risk of falling is far greater without seizure control afforded by antiepileptic drugs such as valproate.

Dr. Thurman pointed out that the two sets of new findings dovetail well with the AAN guidelines and that if the NHANES data had they been available, they would have been incorporated with other studies the guidelines committee reviewed. “This represents the population of the United States. This is not a convenience sample from a clinic population. WIth that in mind, an unexpectedly large number of middle-aged people — people in their 50s — showed evidence of balance disorder,” he said.

Dr. Thurman said that the modified Romberg might be a useful and economic screen, but the foam pad would have to be standardized to a proper thickness and resistance. He added that this modified test may need further assessment to ensure that it has added value and that it is sensitive in detecting balance disorders with a low rate of false positives.

Gait testing should be an important part of the neurological exam, said Joe Verghese, MB, associate professor in neurology at Albert Einstein College of Medicine, Yeshiva University, who directs the clinical core of the Einstein Aging Study. “It is common to have multiple risk factors for falls, so just testing balance, while important, is not sufficient to assess risk for falls. What we don't know is how different parts of the neurological exam can point to risk of falls” as acknowledged in the AAN practice parameter, he added.

In observing gait, the speed of walking and the variability of strides is key, as the Einstein Aging Study is revealing, Dr. Verghese noted. If a person is walking slowly, or if the stride length varies, these are warning signs that suggest falling risk, he said. Cognitive testing is also important, as impaired cognition associates with risk of falls.



Intervention should also be multipronged to prevent falls, Dr. Verghese said, and should include limiting the number of drugs used and the doses, especially in people already known to be at risk, and to obtain physical therapy, or medication to aid in dementia, when appropriate.

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• Agrawal Y. Disorders of balance and vestibular function in US adults: data from the National Health and Nutrition Examination Survey, 2001–2004. Arch Intern Med 2009; 169(10):938–44.
    • Thurman D. Practice parameter: Assessing patients in a neurology practice for risk of falls (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2008; 70: 473–479.
      ©2009 American Academy of Neurology