CAN A BLOOD TEST PREDICT MS?

A new study has found that analysis of antibodies may help predict whether a person experiencing a single episode of specific neurologic symptoms will ultimately develop clinically definite multiple sclerosis (MS). Because the course of MS is difficult to predict, the “individual prognosis and prediction of clinically definite MS would be of value for counseling and management,” the researchers said. They determined that the “presence of serum antibodies against myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP) in patients with a clinically isolated syndrome predicts the interval to conversion to clinically definite MS.” The study was published in the July 10 New England Journal of Medicine.

The investigators studied 103 patients with a clinically isolated syndrome, MRI lesions suggestive of MS, and positive findings on cerebrospinal fluid analysis to determine the presence of antibodies to MBP and MOG. At baseline, serum samples were collected to test for anti-MOG and anti-MBP antibodies with Western blot analysis, and the lesions detected by cerebral MRI were quantified. In addition, each patient underwent a neurologic examination at baseline and every three months thereafter for symptoms suggestive of relapse.

Patients with anti-MOG and anti-MBP antibodies had relapses more often and earlier than did patients without these antibodies. Twenty-one of 22 patients (95%) with anti-MOG and anti-MBP antibodies had a relapse within a mean of 7.5 months, and 35 of 42 patients (83%) with only anti-MOG antibodies had a relapse within 14.6 months. In contrast, only 23% of antibody seronegative patients relapsed, and the mean time to relapse was 45.1 months. Also, patients who were seropositive for both antibodies had higher mean numbers of lesions on MRI than did those who were seronegative. The researchers believe that because the spread of antigens early in the course of a disease “correlates with the progression of disease,” the predictive value of these antibodies may be relevant “for counseling purposes or for early treatment to prevent the disease from progressing.”

Berger T, Rubner P, Schautzer F, et al. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med. 2003;349:139-145.

NSAIDS LOWER RISK OF ALZHEIMER’S DISEASE

Non-steroidal anti-inflammatory drugs (NSAIDs) lower the risk for Alzheimer’s disease, according to research published in the July 19 issue of BMJ. In a systematic review, researchers from the Department of Clinical Epidemiology at Royal Victoria Hospital in Montreal, as well as the University of Toronto and the University of Washington in Seattle, identified 15 studies investigating the relationship between NSAID or aspirin use conducted between 1996 and 2002. Of these, nine studies looked at all NSAID use in adults older than 55. Six of the nine studies were cohort studies totaling 13,211 participants, and three were case-control studies totaling 1,443 participants. Eight studies dealt with aspirin use.

The researchers’ meta-analysis of the data consisted of three separate analyses: first, exploring risk of Alzheimer’s disease in users of all NSAIDs; second, examining this risk among aspirin users; and third, evaluating the risk in terms of duration of NSAID use. The results for the cohort and case-control studies were generally similar for both NSAID analyses, with little statistical heterogeneity, the researchers pointed out.

The pooled relative risk of Alzheimer’s disease among users of NSAIDs was 0.72. Among short-term users (less than one month) the relative risk was 0.95; among intermediate (mostly less than 24 months) and long-term users (more than 24 months), the relative risks were 0.83 and 0.27, respectively. The pooled relative risk in the aspirin studies was 0.87.

The researchers concluded that NSAIDs offer some protection against Alzheimer’s disease, and that the benefits may increase with the duration of NSAID use. However, appropriate dose, duration, and the ratios of risk to benefit remain unclear, they cautioned.

Aspirin also registered a protective effect against Alzheimer’s disease, they noted—though it did not reach statistical significance, likely because of the small number of studies that specifically evaluated the effects of aspirin, the researchers said.

Etminan M, Gill S, Samii A. Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer’s disease: systematic review and meta-analysis of observational studies. BMJ. 2003;327:128-132.

CAN BRAIN OVERGROWTH PREDICT AUTISM?

Small head circumference at birth, followed by a sudden and excessive increase in head circumference during the first year of life, may be linked to the development of autism in children, according to a study published in the July 16 JAMA. Investigators sought to determine whether brain overgrowth precedes the first clinical signs of autism spectrum disorder and whether the rate of overgrowth is related to clinical outcome in early childhood.

Researchers studied the medical records of 48 2- to 5-year olds who had been diagnosed with autism spectrum disorders. Each of the children in the study had been a participant in previous MRI studies reporting age-related changes in the brain in autism. Using the Centers for Disease Control and Prevention growth charts for healthy children and the Fels Longitudinal Study of head circumference, the investigators compared the children’s head circumference measurements at birth and during various points in their first year of life with 51 infants born between 1980 and 2001.

They found that the head size of the autistic children at birth was only, on average, in the 25th percentile. During the first year of life, however, these same children experienced sudden, rapid, and excessive brain growth that put them in the 85th percentile at about 12 to 14 months of age. The researchers noted that the abnormal brain growth appears to predict the severity of clinical outcomes as well as the degree of brain abnormality at a later age. The rapid, excessive brain growth in infants with autism does not allow enough time for accumulation of experiences and emotions that guide and shape normal behavior. Children later diagnosed with a more severe form of autism demonstrated a faster and greater rate of brain overgrowth during their first year of life, compared with that of children with a milder form of the disorder.

In an accompanying editorial, however, Janet E. Lainhart, MD, stated that the “increased rate of head growth during infancy in autism may be an important concomitant or correlate of autism,” rather than a risk factor. She noted that the increased rate of head growth must precede the onset of autism for it to be considered a risk factor, and there is not enough proof that this is the case. She proceeded to point out that, in some cases, brain abnormalities are present before birth, and some signs of developmental abnormality are seen during infancy in children later diagnosed with autism. These findings, she concluded, “are more useful to researchers attempting to define the underlying developmental neuropathology of autism rather than to physicians trying to identify young children with autism.”

Courchesne E, Carper R, Akshoomoff N. Evidence of brain overgrowth in the first year of life in autism. JAMA. 2003;290:337-344.
Lainhart JE. Increased rate of head growth during infancy in autism. JAMA. 2003;290:393-394.

OBESITY MAY INCREASE ALZHEIMER’S DISEASE RISK IN WOMEN

For women, there is a striking association between being overweight at age 70 and developing Alzheimer’s disease 10 to 18 years later, according to a report in the July 15 Archives of Internal Medicine. Because obesity increases the risk of vascular disorders, which have been associated with Alzheimer’s disease, researchers hypothesized that obesity may be a risk factor for Alzheimer’s disease.

Investigators followed 392 adults (226 female) from age 70 to 88, to determine whether being overweight put them at an increased risk for dementia and Alzheimer’s disease. Body mass index (BMI) for the subjects was determined at age 70, 75, and 79. Physical examinations, blood tests, and neuropsychiatric evaluations for dementia were performed approximately every five years until age 81 and every other year thereafter.

Dementia occurred in 93 patients. Women in the study who developed Alzheimer’s disease between the ages of 79 and 88 were significantly more likely to have been overweight at age 70, as well as at 75 and 79. These women were also much heavier, with a BMI an average of 3.6 units higher than that of women who did not develop dementia. For every unit increase in BMI at age 70, the risk of Alzheimer’s disease increased by 36%. In contrast, there were no differences in BMI between men who were diagnosed with dementia and those who were not.

The investigators noted that the association between high BMI and dementia was found only in women. They hypothesized that this could be due to many factors, including selective survival, metabolic phenomenon, sex differences in body fat distribution, or simply the low number of men in the sample. Previous studies have reported that women with a high BMI are more likely to survive past the age of 70 than are men, giving researchers a greater number of patients to study. Also, the incidence rates of Alzheimer’s disease are significantly higher in women older than 85, supporting the idea of sex differences in the etiology of dementia.

Gustafson D, Rothenberg E, Blennow K, et al. An 18-year follow-up of overweight and risk of Alzheimer disease. Arch Intern Med. 2003;163:1524-1528.

ARE CHEMICAL IMBALANCES RESPONSIBLE FOR SLEEP DISORDERS?

Chemical imbalances in the brain may be partly to blame for certain life-disrupting sleep disorders, according to two studies by University of Michigan Health System researchers. By studying patients with multiple system atrophy, which is almost always accompanied by sleep disorders, the investigators found links between deficits in brain chemistry and obstructive sleep apnea and REM sleep behavior disorder. Both studies were published in the July 8 Neurology.

Researchers used positron emission tomography (PET), single photon emission computed tomography (SPECT), and detailed sleep studies to examine 13 patients (mean age, 55) with multiple system atrophy and 27 controls. During the three-day study, PET was used with a tracer to measure the density of striatal monoaminergic terminals, while SPECT was used with a tracer to measure the density of thalamic cholinergic terminals. The patients were also studied with laboratory-based polysomnography for two consecutive nights. Researchers measured the rate of the severity of REM atonia loss and the severity of obstructive sleep apnea, using the apnea-hypopnea index during sleep.

Patients with multiple system atrophy had a far lower density of neurons that produce dopamine and acetylcholine than did the controls. The investigators found that the greater the lack of neurons, the worse the patient’s sleep problems were. Those with the fewest dopamine-producing neurons in the striatum had the worst REM sleep behavior disorder symptoms of thrashing, talking, and violent flailing while they slept; patients with the lowest levels of acetylcholine-producing neurons in the brain stem had the most interruptions in their breathing during sleep. The researchers noted, however, that the findings only show a correlation, not a causation, between brain chemistry and sleep disorders.

Gilman S, Chervin RD, Koeppe RA, et al. Obstructive sleep apnea is related to a thalamic cholinergic deficit in MSA. Neurology. 2003;61:35-39.
Gilman S, Koeppe RA, Chervin RD, et al. REM sleep behavior disorder is related to striatal monoaminergic deficit in MSA. Neurology. 2003;61:29-34.

PROTEIN “FINGERPRINTING” PREDICTS HIV-ASSOCIATED DEMENTIA

Patients with HIV and dementia have distinct protein patterns in their blood that set them apart from patients with no symptoms of dementia, according to a study at the University of Puerto Rico Medical Sciences Campus in San Juan. The investigators believe that the new research technique “proteomics fingerprinting” may be a possible screen for the first signs of cognitive impairment in patients with HIV. Cognitive impairment affects about 10% to 15% of people with HIV.

Researchers recruited 31 Puerto Rican women between the ages of 21 and 45 for the study, which was published in the June 24 Neurology. Within three months, complete neurologic testing was performed and blood samples were obtained. Nine of the women had HIV with relatively high levels of cognitive impairment, 12 had HIV without dementia, and 10 control subjects were HIV-negative and had no cognitive impairment. Researchers then used proteomics to map patterns of activity for particular groups of monocyte-derived macrophages, providing them with a molecular fingerprint unique to each patient.

Proteomic analysis showed that of the 177 proteins examined in the study, 38 proteins exhibited different activity levels—represented as peaks—in the HIV-associated dementia groups than in patients without dementia. In particular, a 4348 Da protein separated the two groups with a sensitivity of 100% and a specificity of 75%. Investigators do not know how and when these protein profiles appear in the monocytes, though they believe that “future works will determine the significance of the protein peaks discovered in disease pathogenesis and when and under what conditions an HIV-infected individual would succumb to cognitive impairment.”

NR

Luo X, Carlson KA, Wojna V, et al. Macrophage proteomic fingerprinting predicts HIV-1-associated cognitive impairment. Neurology. 2003;60:1931-1937.

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