EARLY TREATMENT PREFERRED FOR MS

Citing a lack of evidence distinguishing multiple sclerosis (MS) patients who need early treatment from those who do not, E. Steve Roach, MD, favored early treatment for MS in an editorial accompanying a debate on the topic, published in the April Archives of Neurology.

Sean J. Pittock, MD, and colleagues first offered reasons to delay treatment of MS until the course of the disorder becomes clearer. They pointed out the possible tendency of MS to have a favorable natural history; the partial short-term—and unproven long-term—effectiveness of disease-modifying drugs; the drawbacks of the expense of treatment, its adverse effects, and the riddle of neutralizing antibodies; and the possibility that MRI monitoring may identify patients who are in need of treatment.

Dr. Pittock’s team stated, "Until properly designed studies demonstrate unequivocal and long-term benefits on disability progression, we support observation and monitoring for patients with clinically isolated syndrome and relapsing-remitting multiple sclerosis with recent diagnosis and without indicators of an aggressive course."

However, Elliot M. Frohman, MD, and colleagues countered that the majority of patients with MS develop significant disability. In addition, they noted that irreversible damage is done in the early stages of the disease, even if patients appear to be doing well, and treatment is most effective in the early disease stages, when the drugs are able to limit relapse occurrence and severity.

"Ultimately, by the time untreated patients are ‘bad’ enough to justify receiving therapy, they may no longer be optimal responders," Dr. Frohman’s team rejoined. "We acknowledge that multiple sclerosis disease-modifying therapy is expensive. However, disability progression, loss of gainful employment, and intellectual deterioration are substantially more expensive."

Dr. Frohman and colleagues also noted, "The available drugs provide tangible benefits to patients. They are well tolerated and do not appear to have any long-term adverse impact on health in the vast majority."

In the accompanying editorial, Dr. Roach pointed out, "What has allowed us to alter our treatment approach for seizures is the accumulation of specific information that not everyone needs aggressive treatment and that others can safely halt therapy. Without such evidence for individuals with multiple sclerosis, it will be difficult to know for sure whether it is ever safe to defer treatment. While it would be wonderful if we could avoid treating some patients with multiple sclerosis, until we can distinguish these individuals from the others, it is probably better to offer treatment to all patients except in the setting of a clinical trial."

Suggested Reading
Frohman EM, Havrdova E, Lublin F, et al. Most patients with multiple sclerosis or a clinically isolated demyelinating syndrome should be treated at the time of diagnosis. Arch Neurol. 2006;63:614-619.
Pittock SJ, Weinshenker BG, Noseworthy JH, et al. Not every patient with multiple sclerosis should be treated at time of diagnosis. Arch Neurol. 2006;63:611-613.
Roach ES. Early multiple sclerosis: to treat or not to treat? Arch Neurol. 2006;63:619.

ABNORMAL GLUCOSE METABOLISM MAY BE RISK FACTOR IN CHRONIC NEUROPATHY

In patients with chronic idiopathic axonal polyneuropathy, abnormal glucose metabolism may be a risk factor, according to a report published online in the June 12 Archives of Neurology.

Charlene Hoffman-Snyder, MSN, NP-BC, and colleagues conducted a two-year retrospective study, in which 60 women and 40 men had chronic idiopathic axonal polyneuropathy. Patients underwent a fasting glucose test and a two-hour oral glucose tolerance test. Thirty-nine patients were found to have abnormal fasting plasma glucose metabolism using the 2003 American Diabetic Association guidelines; three of these patients had diabetes mellitus, while the rest had impaired fasting glucose. However, according to the two-hour oral glucose tolerance test, 62 patients met the criteria for abnormal fasting plasma glucose metabolism; 24 had diabetes mellitus, and the remaining 38 had impaired glucose tolerance. Overall, an abnormal glucose metabolism rate of 62% was found in patients with chronic idiopathic axonal polyneuropathy, compared with a rate of 33% in the general age-matched population, published by the CDC. Sensorimotor, pure sensory, and small-fiber neuropathy subtypes of chronic idiopathic axonal polyneuropathy all demonstrated similar abnormal glucose metabolism rates.

Ms. Hoffman-Snyder and colleagues pointed out that the two-hour oral glucose tolerance test is a more valuable detector of impaired glucose metabolism in chronic neuropathy patients with unknown cause. "The two-hour oral glucose tolerance test is often avoided by busy health care professionals, perhaps because of the inconveniences posed by the testing procedure," stated the researchers. "The fasting plasma glucose level alone does not always identify patients with impaired glucose tolerance and neither does the two-hour oral glucose tolerance test always detect patients with impaired glucose metabolism. Both tests are, however, useful to detect hyperglycemia and the consequences of disordered glucose metabolism."

Ms. Hoffman-Snyder’s team also pointed out that changes in diet and exercise have been shown in recent studies to normalize glucose metabolism and limit neuropathic pain, which underlines the importance of identifying abnormalities in glucose metabolism.

"This retrospective analysis of patients with chronic idiopathic axonal polyneuropathy adds to the increasing body of evidence that shows a higher prevalence of abnormal fasting glucose metabolism in patients with chronic idiopathic axonal polyneuropathy in comparison with an age-matched US population," concluded Ms. Hoffman-Snyder and colleagues. "Thus, impaired fasting glucose or impaired glucose tolerance may be risk factors for the development of chronic idiopathic axonal polyneuropathy.... Additional studies with age-matched case-control subjects are warranted before definite causal relationships between peripheral nerve dysfunction and abnormal glucose metabolism can be fully accepted."

Suggested Reading
Hoffman-Snyder C, Smith BE, Ross MA, et al. Value of the oral glucose tolerance test in the evaluation of chronic idiopathic axonal polyneuropathy. Arch Neurol. 2006 June 12; [Epub ahead of print].

HEALTHY LIFESTYLE PROGRAM MAY IMPROVE COGNITIVE FUNCTION

A short-term healthy lifestyle program combining mental and physical exercise, stress reduction, and a healthy diet may significantly improve cognitive function and brain metabolism, according to a study published in the June American Journal of Geriatric Psychiatry.

Gary W. Small, MD, and colleagues included 17 persons ages 35 to 69 without dementia but with mild self-reported memory complaints and normal baseline memory performance scores. The participants were randomly assigned to either a usual lifestyle routine or to a 14-day program combining a brain-healthy diet plan, relaxation exercises, cardiovascular conditioning, and mental exercise. Subjects assigned to the healthy lifestyle program objectively demonstrated greater word fluency, and their [fluorine-18]fluorodeoxyglucose positron emission tomography scans showed a 5% decrease in activity in the left dorsolateral prefrontal cortex. By contrast, no significant change in any of the measures was observed in the control group.

Dr. Small and colleagues pointed out that the reduced resting activity in the left dorsolateral prefrontal cortex could reflect greater cognitive efficiency. In addition, the researchers reported that participants enrolled in the 14-day healthy lifestyle program showed no significant change in subjective cognitive measures. This finding "could reflect the small sample size as well as the insensitivity of the Memory Functioning Questionnaire to measure short-term changes in memory self-awareness," stated the researchers. "Self-awareness of cognitive improvement is helpful in encouraging individuals to continue a healthy lifestyle beyond a two-week period," they noted, while "worry and concern about memory performance has been associated with worse objective memory performance scores."

In a study published in the May 22 Archives of Internal Medicine, Li Wang, MS, and colleagues suggested that poor physical function may precede the onset of dementia and Alzheimer’s disease and that higher levels of physical function may be associated with a delayed onset. However, Dr. Small’s team noted that future longitudinal studies are needed to determine both the long-term effects of a healthy lifestyle program and whether such a program could eventually lower a person’s risk for dementia.

"To our knowledge, this is the first study to show that combining several healthy lifestyle strategies will change measures of cognitive and brain function in a relatively brief time period," stated Dr. Small and colleagues. "The results suggest that a program combining mental and physical exercise, stress reduction, and healthy diet can have significant short-term effects on brain metabolism and cognitive performance."

Suggested Reading
Small GW, Silverman DHS, Siddarth P, et al. Effects of a 14-day healthy longevity lifestyle program on cognition and brain function. Am J Geriatr Psychiatry. 2006;14:538-545.
Wang L, Larson EB, Bowen JD, van Belle G. Performance-based physical function and future dementia in older people. Arch Intern Med. 2006; 166:1115-1120.

PARKIN MUTATION HETEROZYGOSITY INFLUENCES AGE AT ONSET IN PARKINSON'S DISEASE

Results of the GenePD Study of patients with familial Parkinson’s disease revealed that mutations in the parkin gene "are not rare in multiply affected sibships, and that heterozygous mutation carrier status in PARK2 significantly influences age at onset of Parkinson’s disease." The findings were published in the June Archives of Neurology.

Mei Sun, MD, PhD, of the Molecular Neurogenetics Unit, Massachusetts General Hospital, Boston, and colleagues in the international GenePD Study evaluated the effects of parkin mutations in 183 of 329 families with at least two Parkinson’s disease–affected members. Two criteria were used in the selection process: (1) families with affected siblings sharing two alleles identical by state at the PARK2 locus and (2) families in which one person had onset before age 54.

At least one parkin mutation was found in 23 of 183 patients (12.6%), the investigators reported. Among mutation-positive families, 10 (43%) were compound heterozygotes, three (13%) were homozygotes, and 10 (43%) were heterozygotes.

Patients with parkin mutations developed Parkinson’s disease at an average age of 42.9—a mean 11.7 years earlier than patients with no mutation, said Dr. Sun. Patients with two or more mutations had an onset 13.2 years earlier than patients with a single mutation.

"Parkin mutations are not rare in this selected subset of familial Parkinson’s disease samples. Homozygous and compound heterozygous parkin gene mutations are associated with early-onset Parkinson’s disease (mean onset age, 36)," the investigators said. Though parkin mutations were presumed recessive, the data on the heterozygous individuals suggest that the gene’s effect may be stronger than previously recognized, Dr. Sun noted. Screening for mutations in the gene may help identify those at risk for Parkinson’s disease.

If the results of this study are confirmed, they "will require a reexamination of the genetic data associated with Parkinson’s disease to take into account the possibility that heterozygous mutations in autosomal recessive genes such as parkin and PINK1 affect the susceptibility and age of onset of Parkinson’s disease," wrote Roger N. Rosenberg, MD, and Uwe Beffert, PhD, both of the University of Texas Southwestern Medical Center, Dallas, in an accompanying editorial. "These findings are provocative and add a new genetic dimension to the pathogenesis of Parkinson’s disease."

Suggested Reading
Beffert U, Rosenberg RN. Increased risk for heterozygotes in recessive Parkinson disease. Arch Neurol. 2006;63:807-808.
Sun M, Latourelle JC, Wooten GF, et al. Influence of heterozygosity for parkin mutation on onset age in familial Parkinson disease. Arch Neurol. 2006; 63:826-832.