Spring Meetings Bring New Research Findings to Clinicians

May 1, 2005

Recent medical meetings provided platforms for researchers to present their latest findings and for practicing physicians to catch up on the latest developments in their fields. Following are summaries of some of those presentations, and more will follow in the next issue.

Recent medical meetings provided platforms for researchers to present their latest findings and for practicing physicians to catch up on the latest developments in their fields. Following are summaries of some of those presentations, and more will follow in the next issue. The summaries included here are from the meetings of the:

*American Pain Society (APS), March 30-April 2, Boston.

*American Academy of Neurology (AAN), April 9-16, Miami Beach.

*American Association of Neurological Surgeons (AANS), April 16-21, New Orleans.

NSAIDS AND PARKINSON DISEASE: A CLARIFICATION

Ibuprofen may be the only NSAID that offers protection against the onset of Parkinson disease (PD), according to researchers from Harvard University. The group previously reported that the broader group of nonaspirin NSAIDs had a protective effect. In the current study, presented at the AAN meeting, the team analyzed data for more than 146,000 persons enrolled in the American Cancer Society's Cancer Prevention Study II. They identified 413 incident cases of PD from more than 1.2 million person-years of follow-up. (The citation for the published abstract is Chen H, Jacobs E, Schwarzschild MA, et al. Nonsteroidal antiinflammatory drugs and the risk of Parkinson's disease. Neurology. 2005;64[suppl 1]:A311.)

Compared with persons who do not use NSAIDs, the relative risk of PD developing in ibuprofen users was 0.65 (P = .005). The relative risk for persons who used NSAIDs other than ibuprofen, however, was not significantly different from that for nonusers. The earlier study, published in the August 2003 issue of Archives of Neurology, analyzed data for more than 142,000 persons enrolled in the Health Professionals Follow-up Study and the Nurses' Health Study. A total of 415 cases of PD were documented. The Harvard researchers found that the relative risk of PD developing was 0.55 in persons who reported regular NSAID use, compared with nonusers. That study also found a relative risk of 0.56 in those who took more than 2 aspirin tablets per day, but the finding was not statistically significant.

--Jordana Bieze Foster

CANADA APPROVES CANNABIS

Sativex is effective for neuropathic pain in patients with multiple sclerosis (MS), according to a study presented at the APS meeting. The finding turned out to foreshadow more good news for the makers of the oromucosal cannabis extract product: it was approved by Health Canada on April 19 as an adjunct treatment for neuropathic pain in MS. The approval was the first in the world for Sativex, which is manufactured by GW Pharmaceuticals in Salisbury, UK. The agent will be distributed in Canada by Bayer.

The study researchers, a team from Gartnavel General Hospital in Glasgow, found significant improvements in mean levels of peripheral neuropathic pain, central neuropathic pain, and spasticity in 118 patients with MS and/or chronic pain who had been enrolled in an open-label study for at least 52 weeks (Table 1). The mean number of sprays of the product used per day actually decreased from week 12 to week 52, suggesting that patients did not develop a tolerance to the drug, which delivers 2.7 mg of tetrahydrocannabinol and 2.5 mg of cannabidiol per 100 µL dose.

A multicenter randomized, placebo-controlled UK trial presented at the AAN meeting also found that 35 days of Sativex treatment effectively reduced the intensity of both peripheral neuropathic pain and of mechanical allodynia in 105 patients. Mean changes in symptom scores from baseline were significantly greater in patients treated with Sativex than in those who received placebo (Table 2). (The full citation of the published abstract is Nurmikko TJ, Serpell MG, Hoggart B, et al. A multi-centre, double-blind, randomized placebo-controlled trial of oro-mucosal cannabis-based medicine in the treatment of neuropathic pain characterized by allodynia. Neurology. 2005;64[suppl 1]:A374.)

GW Pharmaceuticals announced in February that it would be taking preliminary steps toward making a run at the US market, reasoning that the research supporting Sativex will be strong enough to win over the FDA despite the government's historical reluctance to endorse cannabis-based medicines.

The strained relations between cannabis advocates and the US government grew even more contentious in late April, as the American Civil Liberties Union publicly challenged the Drug Enforcement Administration (DEA) because it refused to allow a University of Massachusetts professor to grow research-grade marijuana. Plant and soil sciences professor Lyle Craker, PhD, filed a lawsuit against the DEA last summer. Researchers involved in 2 FDA-approved projects have been unable to obtain marijuana from the National Institute on Drug Abuse--currently the only supplier for research-grade marijuana in the United States. They said they would welcome an independent source.

--Jordana Bieze Foster

ESSENTIAL TREMOR

Individuals with essential tremor (ET) are twice as likely to develop dementia than are persons who do not have the disorder, according to a study presented at the AAN meeting. The Neurological Disorders in Central Spain (NEDICES) study spanned 3 years and included 202 elderly persons with ET and 3541 without. Over that period, dementia developed in 7.4% of those with ET, compared with 3.5% of the control group. Dementia was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders. The risk of incident dementia was assessed using a Cox proportional hazards model. (The full citation for the published abstract is Benito-Leon J, Bermejo-Pareja F, Louis ED. Essential tremor is associated with increased risk of incident dementia in a community-based longitudinal study. Neurology. 2005;64[suppl 1]: A253-A254.)

The study was the first to suggest that ET, which affects 1 in 5 persons over age 65, is associated with an increased risk of incident dementia. "We don't know yet whether the dementia is due to the same underlying problem that is causing the essential tremor or whether it is caused by another problem," said study author Julian Benito-Leon, MD, PhD, of Mostoles General Hospital in Madrid. The study findings were presented by Elan D. Louis, MD, deputy director of the Neurotoxicology/Neurodegenerative Disease Research Core at Columbia University.

Two neurologists contacted for comment had varying opinions on the value of the results: "These findings are quite surprising since ET has never previously been associated with increased risk of dementia," said Joseph Jankovic, MD, professor of neurology and director of the Parkinson's Disease Center and Movement Disorders Clinic at Baylor College of Medicine in Houston. "Since this is clearly not my experience, evaluating thousands of ET patients over the past 30 years, I would like to have the results verified and replicated by another study before recommending dementia screening in all patients with ET. It would be interesting to find out whether those ET patients who showed evidence of cognitive deficit also exhibited parkinsonian features. I personally believe that a subset of ET patients has a higher risk for developing parkinsonism [evidence partly reviewed in Jankovic J. Essential tremor: A heterogenous disorder. Mov Disord. 2002;17:638-644], and since some PD patients al- so develop dementia, this could potentially provide an explanation for the possible link between ET and dementia."

Sami I. Harik, MD, professor and chair of neurology at the University of Arkansas for Medical Sciences in Little Rock, had this to say: "If the methodology of the study and the statistical analyses are adequate and appropriate, this study will have important applications, both practical and theoretical. From the practical point of view, neurologists should at least give detailed attention to the cognitive state of patients that they treat for essential tremor. Early recognition and treatment of dementia in some of these patients may improve their quality of life. From the theoretical point of view, the association may eventually be even more important. It may shed light on the relationships among a number of degenerative brain conditions that appear later in life."

--Kathy Stone

TRAUMATIC BRAIN INJURY

Two presentations at the AANS meeting shed more light on risks and outcomes of traumatic brain injury (TBI) caused by trauma, violence, and accidents. Building on research that has shown gender differences in physiologic changes in cerebral blood flow (CBF), researchers from Los Angeles and Haifa, Israel, tracked 90 men and 26 women admitted to University of California, Los Angeles, Hospital and Rambam Hospital within 24 hours of moderate to severe injury to determine how men and women differ regarding TBI outcomes.

The Los Angeles investigators used the 133-xenon washout technique, placing a band of probes around the patients' heads, and using a computer to calculate the rate of 133-xenon clearance in the brain, rendering a CBF volume measurement. The Haifa researchers used a dual-beam Doppler technique, calculating CBF via an ultrasonographic device placed on the patient's head. Measurements were taken every 12 hours for the first 2 days, then almost daily through day 9. Investigators who were blind to the patients' metabolic and other clinical data assessed the neurologic outcomes 6 months postinjury employing the Glasgow Outcome Scale (GOS), which they used for linear (1 = death, 5 = good recovery) and dichotomized (GOS 1-5 = death-favorable) assessments.

Older women in particular showed a steeper decline in CBF and GOS scores than did men. Mean GOS scores ranged from 3.9 for women younger than 25 down to 1.6 for women aged 60 and older. The implications of this study are that increasing age may affect women who have had a TBI more adversely than men and that CBF is a stronger predictor of outcome in women than in men, according to Deborah Lee, one of the Los Angeles researchers.

In the other study, Deborah L. Benzil, MD, associate professor and associate director of neurosurgery at New York Medical College, Valhalla, and colleagues analyzed the records of 178,642 patients treated for TBI between January 1991 and December 2001, as listed in the New York Statewide Planning and Research Cooperative System database. Head injury treatment guidelines were established in 1994, and many states, including New York, have adopted regional trauma centers as a way to improve patient care.

These researchers used the Relative Head Injury Severity Scale (RHISS), which classifies injuries on a 0-to-3 (0, no injury; 3, severe) scale, and the Injury Severity Score to assess probability of survival. RHISS data showed that the rate of mild head injuries declined from 66.8% in 1991 to 42.3% in 2001. Meanwhile, the rate of moderate to severe head injuries increased reciprocally from 33.2% to 57.7%. The total number of cases dropped from 20,502 in 1991 to 13,585 in 2001--a 33% decrease, and the average age at occurrence increased from 35.4 years in 1991 to 44.5 years in 2001.

In summary, fewer but older patients experienced TBI during the study period. Because of an increase in the severity of the injuries, more were likely to die.

However, according to Benzil, the results also show that preventive measures, such as seat belts and air bags in automobiles, and activism by groups such as Mothers Against Drunk Driving have been effective in reducing the number of injuries and that the adoption of TBI treatment guidelines, along with the establishment of organized trauma systems, have improved patient outcomes despite the increase in severity of injuries. "In New York State, the development of the trauma system led to a smaller number of hospitals taking care of a higher volume of patients with TBI, resulting in lower mortality," she said.

--Larry Hand