POSITIVE RESPONSE TO EPILEPSY MEDICATION DOES NOT ENSURE GOOD PROGNOSIS

A substantial proportion of localization-related epilepsy may not become clearly intractable for many years after onset, proving to researchers that early successful treatment and control of epileptic seizures with appropriate medications does not necessarily guarantee that seizures will always be controlled by those medications. The investigators examined the histories of a series of adult patients who underwent resective surgery for refractory localization-related epilepsy to determine how much time elapsed before the disease became intractable. The study appeared in the January 28 Neurology.

Anne T. Berg, PhD, and colleagues examined 333 adults who underwent surgery for partial epilepsy occurring in a localized area of the brain. Researchers collected data through medical records and personal interviews with the patients. The interview collected demographic characteristics and information about the features of each patient’s epilepsy. The investigators concentrated on examining the type of surgery, whether there was a history of febrile seizures or mesial temporal sclerosis, and age at onset. They also defined time to intractability as “the time between the occurrence of the second unprovoked seizure … and failure of the second antiepileptic drug.”

The researchers found that the younger the age at onset, the longer the intractability time (average time to drug failure, 9.1 years). In addition, approximately one quarter of the patients had experienced a period of at least one year without having a seizure. The investigators also determined that “the proportion with both febrile seizures and hippocampal atrophy was greater the younger the age at onset.” They feel that an early benign epilepsy course does not necessarily guarantee a good long-term outcome, and suggest this initial benign course itself may help to determine which patients will develop intractable temporal lobe epilepsy.

Suggested Reading
Berg AT, Langfitt J, Shinnar S, et al. How long does it take for partial epilepsy to become intractable? Neurology. 2003; 60:186-190.

BENEFITS OF TREATING BEHAVIORAL, FUNCTIONAL PROBLEMS IN PATIENTS WITH ALZHEIMER’S DISEASE

Cholinesterase inhibitors have a beneficial impact on behavioral problems and the ability to perform everyday tasks in patients with Alzheimer’s disease, according to a study published in the January 8 JAMA. Investigators sought to determine the efficacy of cholinesterase inhibitors, which have been shown to treat memory loss, disorientation, and loss of language skills, for functional and neuropsychiatric outcomes in patients with mild to moderate Alzheimer’s disease.

Researchers conducted a meta-analysis of approximately 3,000 titles and abstracts. They identified 29 clinical trials of outpatients who were diagnosed as having mild to moderate probable Alzheimer’s disease and were treated for at least one month with a cholinesterase inhibitor. Sixteen of the trials included neuropsychiatric outcomes, which were measured with the Neuropsychiatric Inventory and the Alzheimer Disease Assessment Scale, noncognitive. Fourteen trials used activities of daily living scales to measure functional outcomes, while thirteen trials used instrumental activities of daily living scales.

When assessing neuropsychiatric outcomes, the investigators found that patients randomized to cholinesterase inhibitors improved 1.72 points on the Neuropsychiatric Inventory and 0.03 points on the Alzheimer Disease Assessment Scale, noncognitive, compared with patients taking placebo. While determining functional outcomes, they observed that patients taking cholinesterase inhibitors improved 0.10 standard deviations on activities of daily living scales and 0.09 standard deviations on instrumental activities of daily living scales, compared with placebo. Researchers conducted sensitivity analyses to discover whether the meta-analyses were influenced by choices in methodology and saw that there was no change in statistical significance; they also determined that there was no difference in efficacy among different types of cholinesterase inhibitors. The investigators believe, based on the results of their analyses, that cholinesterase inhibitors should be considered a therapeutic option for patients with moderate to mild Alzheimer’s disease.

Suggested Reading
Trinh N, Hoblyn J, Mohanty S, Yaffe K. Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta-analysis. JAMA. 2003;289:210-216.

MODERATE ALCOHOL CONSUMPTION PROTECTS AGAINST STROKE

Having two drinks a day can cut the risk of total and ischemic stroke by almost 30%, but having five or more glasses of alcohol per day raises the risk of ischemic stroke by approximately 70%, according to a study in the February 5 JAMA. Researchers have reported that other studies examining the association between alcohol consumption and stroke have given conflicting results; this meta-analysis of epidemiologic studies sought to determine the relative risk of stroke at various levels of alcohol consumption.

Investigators analyzed 35 published studies that appeared between 1966 and 2002, in which total, ischemic, or hemorrhagic stroke was an end point and the relative risks of stroke associated with alcohol consumption were reported. Alcohol consumption was categorized into five groups: none (control), less than 12 g/d, 12 to 23 g/d, 24 to 60 g/d, and more than 60 g/d, with 12 grams equivalent to one drink. The investigators performed a weighted meta-regression analysis to “examine the association between alcohol consumption and the natural logarithm of the relative risk of stroke.” They found this method advantageous because it enabled the researchers to identify relationships between exposure levels and relative risks, such as J- or U-shaped curves.

The investigators determined that the association between alcohol consumption and relative risk of ischemic stroke was J-shaped. Compared with the control group, alcohol consumption of less than one drink per day or one to two drinks per day was significantly associated with a decreased relative risk of stroke, while consumption of more than five drinks per day was significantly associated with an increased relative risk of total stroke. They also found that the relative risk of hemorrhagic stroke increased linearly with increasing alcohol consumption, and those consuming more than five drinks per day had the highest relative risk.

Suggested Reading
Reynolds K, Lewis LB, Nolen JDL, et al. Alcohol consumption and risk of stroke: a meta-analysis. JAMA. 2003;289: 579-588.

MEMORY NEED NOT BE IMPAIRED IN OLD AGE

The relationship between cognitive and functional performance and clinical diagnosis in nonagenarians follows patterns previously described in younger samples of healthy individuals, according to a study by the Mayo Clinic. Researchers hypothesized that individuals older than 90 diagnosed with mild cognitive impairment “retain the pattern of similarity to subjects with dementia on tests of learning and memory,” and similarity to healthy subjects on activities of daily living and on measures of cognition. They also sought to determine whether testing for dementia or pre-Alzheimer’s disease conditions could be conducted in this age-group. The study was published in the February 11 Neurology.

The investigators performed neurologic evaluations, neuropsychometric testing, and functional assessments on 111 people diagnosed as either normal, having mild cognitive impairment, or with dementia. Data were collected from the Mini-Mental State Examination, the Hearing Handicap Inventory for the Elderly–Screening Version, the Record of Independent Living, the Trailmaking Test, the Mattis Dementia Rating Scale, and the Modified Free and Cued Selective Reminding Test.

The researchers found that on the Record of Independent Living, capacity to carry out activities of daily living was worse for patients with dementia than for the mild cognitive impairment and healthy groups; however, functional capacity did not differ between the healthy group and the mild cognitive impairment group. Scores on the Mini-Mental State Examination, Trailmaking Test, and the Mattis Dementia Rating Scale were worse in the dementia group compared with both the healthy group and the mild cognitive impairment group, but again there was no difference in these scores between the healthy group and the mild cognitive impairment group. The researchers believed that “in spite of the advanced age of the cohort, it was possible to observe the full cognitive continuum from healthy to mild cognitive impairment to dementia” and that the cognitive performance of the three groups was “comparable to that of younger individuals.”

Suggested Reading
Boeve B, McCormick J, Smith G, et al. Mild cognitive impairment in the oldest old. Neurology. 2003;60:477-480.

TREATED FAMILIAL HYPERCHOLESTEROLEMIA CONFERS NO ADDED RISK OF FATAL STROKE

Patients with treated familial hypercholesterolemia are not at an increased risk of fatal stroke, according to a study in the January Stroke. Researchers have noted that there are few reported data on the incidence of stroke related to hypercholesterolemia, and what data do exist are contradictory. The investigators reported stroke mortality in the largest published cohort of men and women with treated familial hypercholesterolemia.

The cohort consisted of 1,569 patients with definite and 1,302 patients with possible familial hypercholesterolemia who were recruited from outpatient lipid clinics in the United Kingdom. The patients were followed for a median of 7.9 years. During this time, 94.2% of the patients had received dietary advice and 54.6% had been prescribed lipid-lowering drug therapy. Researchers calculated the mortality rate and the standardized mortality ratio for the patients, as well as the cause of death.

By the end of the follow-up, there were 169 deaths, including nine fatal strokes. Five strokes occurred in patients with definite and in four patients with possible hypercholesterolemia; three of these deaths occurred in patients who had a history of previous stroke. The stroke mortality rate was 0.39 per 1,000 person-years, and researchers found that there was no significant difference in the ratio of observed to expected number of strokes in the cohort. However, because only nine fatal strokes occurred, the investigators feel that they cannot exclude the possibility of a small excess risk.

NR

Suggested Reading
Huxley RR, Hawkins MH, Humphries SE, et al. Risk of fatal stroke in patients with treated familial hypercholesterolemia: a prospective registry study. Stroke. 2003;34:22-27.

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