Linda A. Hershey

Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis. Veterans Affairs Cooperative Studies Program 309 Trialist Group

OBJECTIVE To determine whether carotid endarterectomy provides protection against subsequent cerebral ischemia in men with ischemic symptoms in the distribution of significant (greater than 50%) ipsilateral internal carotid artery stenosis. DESIGN Prospective, randomized, multicenter trial. SETTING Sixteen university-affiliated Veterans Affairs medical centers. PATIENTS Men who presented within 120 days of onset of symptoms that were consistent with transient ischemic attacks, transient monocular blindness, or recent small completed strokes between July 1988 and February 1991. Among 5000 patients screened, 189 individuals were randomized with angiographic internal carotid artery stenosis greater than 50% ipsilateral to the presenting symptoms. Forty-eight eligible patients who refused entry were followed up outside of the trial. OUTCOME MEASURES Cerebral infarction or crescendo transient ischemic attacks in the vascular distribution of the original symptoms or death within 30 days of randomization. INTERVENTION Carotid endarterectomy plus the best medical care (n = 91) vs the best medical care alone (n = 98). RESULTS At a mean follow-up of 11.9 months, there was a significant reduction in stroke or crescendo transient ischemic attacks in patients who received carotid endarterectomy (7.7%) compared with nonsurgical patients (19.4%), or an absolute risk reduction of 11.7% (P = .011). The benefit of surgery was more profound in patients with internal carotid artery stenosis greater than 70% (absolute risk reduction, 17.7%; P = .004). The benefit of surgery was apparent within 2 months after randomization, and only one stroke was noted in the surgical group beyond the 30-day perioperative period. CONCLUSIONS For a selected cohort of men with symptoms of cerebral or retinal ischemia in the distribution of a high-grade internal carotid artery stenosis, carotid endarterectomy can effectively reduce the risk of subsequent ipsilateral cerebral ischemia. The risk of cerebral ischemia in this subgroup of patients is considerably higher than previously estimated.

Cerebrospinal fluid trace element content in dementia: Clinical, radiologic, and pathologic correlations

Using inductively coupled argon plasma emission spectroscopy, we measured 19 trace elements in cerebrospinal fluid of 265 patients who were undergoing diagnostic lumbar puncture. Thirty-three patients had Alzheimer-type dementia (ATD); 16 patients had other dementing illnesses; and 20 had no neurologic disease. There were seven cases of autopsy-proven Alzheimers disease (AD) and eight autopsy controls. We found elevated CSF silicon in 24% of ATD and 71% of AD patients. We found no relationship between CSF aluminum, arsenic, lead, or manganese and ATD, AD, or other dementing illnesses.

Time to hospital arrival, use of thrombolytics, and in-hospital outcomes in ischemic stroke

Objective: To determine the interval between symptom onset and hospital arrival and its relationship to baseline clinical characteristics, use of thrombolysis, and in-hospital outcomes in patients with acute ischemic stroke admitted to the 11 hospitals in the Buffalo metropolitan area and Erie County. Methods: The medical records of 1,590 patients were reviewed to determine the severity of the neurologic deficits (NIH Stroke Scale [NIHSS]), in-hospital mortality, favorable outcome (modified Rankin Scale score of ≤2 at discharge), and strata of time interval between symptom onset and hospital arrival. Results: The time interval between symptom onset and hospital arrival was 0 to 3 hours in 337 (21%) patients, 3 to 6 hours in 177 (11%) patients, 6 to 24 hours in 301 (19%) patients, >24 hours in 420 (26%) patients, and undetermined in 355 (22%) patients. IV (n = 23) and intra-arterial (n = 4) thrombolysis was used in 27 (8%) of the 337 patients that presented within 3 hours of symptom onset. In 1,235 patients with known time interval between symptom onset and hospital arrival, an association (p = 0.008) was observed between strata of increasing time interval and higher proportion of favorable outcomes at discharge. The initial NIHSS score was higher with decreasing interval between symptom onset and hospital arrival (p < 0.0001). Conclusions: A small proportion of patients who present within 3 hours of symptom onset receive thrombolytic therapy. The observation that patients with more severe neurologic deficits and subsequently worse in-hospital outcomes appear to present early after symptom onset to the hospital may have implications for clinical studies.

Efficacy and Safety of Galantamine in Patients with Dementia with Lewy Bodies: A 12-Week Interim Analysis

Observations on the neurochemistry of dementia with Lewy bodies (DLB) have suggested that cholinesterase inhibitors (ChEIs) might be beneficial in treating some clinical symptoms of DLB. A 24-week, multicenter open-label study was designed to assess the safety and efficacy of the ChEI galantamine in patients with DLB, and an interim analysis of results was performed at 12 weeks. Efficacy analyses were performed on data from 25 patients. Scores on the Neuropsychiatric Inventory (NPI-12) improved (decreased) by 7.52 points over the 12 weeks (marginally significant, p = 0.061). NPI-12 scores decreased by half in 12 of the 25 patients. Highly significant improvement was observed in scores on the NPI-4 subscale (delusions, hallucinations, apathy, and depression: p = 0.003). Scores on the Clinician’s Global Impression of Change (CGIC) improved by 0.95 points (significant, p = 0.02). Improvements also were found in secondary efficacy variables, including cognitive, functional, activities of daily living, sleep and confusion assessments. Motor scores, as measured by the UPDRS motor subscale, showed mild improvement, which demonstrates that galantamine has no adverse effect on parkinsonian symptoms. Adverse events generally were transient and of mild-to-moderate intensity. Two of the 25 patients discontinued galantamine because of nausea and anorexia. One serious adverse event was recorded, but it was judged to be unrelated to the study medication.

Efficacy and safety of Galantamine in patients with Dementia with Lewy bodies: A 24-week open-label study

Background: Dementia with Lewy bodies (DLB) is a common dementia of the elderly. A significant cholinergic deficit has been demonstrated that may be responsive to treatment by cholinesterase inhibitors (ChEIs). Methods: A 24-week, open-label study was designed to assess the efficacy and safety of a ChEI, galantamine, in 50 patients with DLB. Results: This study showed beneficial effects with galantamine in 2 of the 3 primary efficacy parameters. The scores on the Neuropsychiatric Inventory (NPI-12) improved by 8.24 points from baseline (p = 0.01) especially in visual hallucinations and nighttime behaviors (p = 0.004). The scores on the Clinician’s Global Impression of Change improved by 0.5 points from baseline (p = 0.01). The third primary efficacy parameter, the Cognitive Drug Research Computerized Cognitive Assessment System, was unchanged from baseline. Adverse events were generally mild and transient. Conclusion: Galantamine appears to be an effective and safe therapy for patients with DLB.

Transcranial doppler: An introduction for primary care physicians

Transcranial Doppler (TCD) is a diagnostic tool that can be used at bedside to assess the cerebral vasculature noninvasively. It is inexpensive, safe, and reliable when compared with other techniques. It can be repeated multiple times and can be used for continuous monitoring if needed. Screening of children with sickle cell disease to assess and prevent ischemic strokes and monitoring for vasospasm after subarachnoid hemorrhage are well established, evidenced based utilizations of TCD. It is useful for the evaluation of occlusive intracranial vascular lesions with many emerging indications in the management of ischemic stroke. TCD with micro-bubble enhancement has comparable sensitivity to transesophageal echocardiogram in detecting right-to-left atrial cardiac shunts. TCD is underused as a clinical tool despite well established indications. The pressure to contain increasing medical cost will likely result in increased utilization of this test in future.

Silicon as a potential uremic neurotoxin: Trace element analysis in patients with renal failure

we analyzed multiple trace elements in tap water, dialysis fluids, and CSF of patients on dialysis and with chronic renal insufficiency. Before placement of a deionizer in the dialysis unit, we found elevated levels of aluminum, barium, copper, silicon, and zinc in tap water and dialysis fluids. These were corrected by the deionizer. CSF silicon content was increased in patients with chronic renal insufficiency and on dialysis; CSF aluminum, barium, copper, and zinc were normal.

Psychiatric disorders and cognitive dysfunction among older, postmenopausal women: results from the Women's Health Initiative Memory Study.

OBJECTIVE To estimate the frequency of depressive symptoms and selected psychiatric disorders in the Womens Health Initiative Memory Study (WHIMS) cohort and related them to cognitive syndromes. DESIGN WHIMS was a randomized, double-blinded, placebo-controlled prevention clinical trial examining whether opposed and unopposed hormone therapy reduced the risk of dementia in healthy postmenopausal women. Participants scoring below a designated cutpoint on a cognitive screener received a comprehensive neuropsychiatric workup and adjudicated outcome of no cognitive impairment, mild cognitive impairment, or probable dementia. PARTICIPANTS Seven thousand four hundred seventy-nine WHIMS participants between age 65 and 79 years and free of dementia at the time of enrollment in WHIMS. Five hundred twenty-one unique participants contributed complete data required for these analyses. MEASURES Depressive symptoms were measured with the 15-item Geriatric Depression Scale and the presence of selected psychiatric disorders (major depression, generalized anxiety, and panic and alcohol abuse) was made using the PRIME-MD. RESULTS The 18% of women had at least one psychiatric disorder with depression being the most common (16%) followed by general anxiety or panic (6%) and alcohol abuse (1%). Depression and the presence of a psychiatric disorder were associated with impaired cognitive status. Participants having a psychiatric disorder were more than twice as likely to be diagnosed with cognitive impairment as those with no psychiatric disorder (odds ratio = 2.06, 95% confidence interval = 1.17-3.60). Older age, white race, and diabetes were also associated with cognitive impairment. CONCLUSION The frequency of a psychiatric disorder is associated with poorer cognitive functioning among older women enrolled in WHIMS. That approximately one in five women had a probable psychiatric disorder, most typically depression, highlights the need for greater detection and treatment efforts in this population.

Stroke prevention in women: Role of aspirin versus ticlopidine

Stroke is the third leading cause of death in North America. Most studies indicate that women are just as likely as men to have an initial stroke but less likely to have a recurrent stroke. Aspirin and ticlopidine are two antiplatelet drugs that reduce the risk of recurrent stroke by 25% to 30%. In some stroke prevention trials, aspirin has been shown to be more effective for men than for women. In contrast, major stroke prevention trials using ticlopidine have demonstrated equal benefit in women and in men. The overall incidence of adverse effects seen with ticlopidine is not significantly different from that observed with aspirin. There are now two effective agents useful in stroke prevention in both men and women.

Parkinsonism Associated with Fluoxetine and Cimetidine: A Case Report:

Fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) are effective for the treatment of depression in the elderly and offer a safer side-effect profile as compared to tricyclics and monoamine oxidase inhibitors. We report a case in which a patient treated with fluoxetine developed parkinsonism following the introduction of cimetidine. Inhibition of hepatic P450 cytochrome enzymes by cimetidine with an increase in serum levels of norfluoxetine may have precipitated this extrapyramidal syndrome, which has been related to agonism of the serotonergic input to nigrostriatal tracts and basal ganglia. Parkinsonism as a side effect of SSRIs occurs infrequently, suggesting an idiosyncratic response resulting from a functional imbalance of serotonergic and dopaminergic activity in susceptible individuals. Careful monitoring of geriatric patients treated with fluoxetine is indicated, particularly for those on high doses, those with impaired hepatic functioning, or those treated with concurrent medications that slow the metabolism of fluoxetine.