Thrombolytic therapy for acute ischemic stroke: why the majority of patients remain ineligible for treatment.

STUDY OBJECTIVES: Thrombolytic therapy has been advocated as an effective treatment for acute ischemic stroke. In an attempt to promote maximum benefit while reducing the risk of hemorrhagic complications, numerous exclusions to the use of thrombolytic therapy for acute ischemic stroke have been promulgated. This study was conducted to identify the number of acute ischemic stroke patients eligible for thrombolytic therapy and to determine the reasons those deemed ineligible were excluded. METHODS: This observational study was conducted from September 15, 1996, to May 1, 1997, at an emergency department with an annual census of 70,000. Patients with a chief complaint suggestive of acute ischemic stroke were categorized as "eligible" if thrombolytic therapy was not contraindicated and could be initiated within 3 hours of symptom onset. Patients were deemed "ineligible" if the time to thrombolytic therapy would have exceeded 3 hours, or if other specific contraindications to thrombolytic therapy were present. For all categories, 95% confidence intervals (95% CI) were determined. RESULTS: Of the 214 patients with acute ischemic stroke who were screened, 6 (2.8%+/-2.2%) were eligible. Ninety-five patients (44%+/-7%) were excluded solely on the basis of the time interval from onset of symptoms to eligibility for thrombolytic therapy exceeding 3 hours. Other common reasons for exclusion included resolution of symptoms in 31 patients (14%+/-4%), intracranial hemorrhage as determined by head computed tomography in 22 (10%+/-4%), and minor symptoms in 20 (9%+/-4%). CONCLUSION: The majority of acute ischemic stroke patients do not meet accepted criteria for thrombolytic therapy. Most are ineligible because of delays in obtaining treatment. Strategies should be devised to reduce the time to treatment if thrombolytic therapy is to achieve widespread use in the treatment of acute ischemic stroke.

Studies in a large family with late-onset Alzheimer disease (LOAD).

A large 10-generation family with late-onset Alzheimer disease (LOAD) inherited as an autosomal dominant trait was evaluated historically, clinically, and genetically. The family origin was traced to a founder couple of French ancestry with approximately 3,000 descendants. Although the transmission of a genetic predisposition to LOAD is demonstrated through male individuals, a predominance of affected women is observed. Currently, 14 individuals, 12 of whom are women, are classified as affected with Alzheimer disease (AD). Among the affected, the age of onset ranged from 55 to 78 years. Genotyping of the apolipoprotein E (APOE) locus demonstrated that homozygotes for the E4 allele (APOE4) developed signs of AD in their late 60s, whereas affected heterozygotes presented with the disease in their 70s. A significantly higher APOE4 frequency was observed in affected family members than in those unaffected (0.79 vs. 0.25, chi 2 = 9.919, p = 0.0016, df = 1). Survival for more than 15 years after diagnosed onset was observed in a number of those affected and can be attributed to an improved environment, including excellent care and management during the disabling phase of illness. Alternatively, it may be an example of the genetic heterogeneity in AD. Complete documentation of large families such as the one presented will facilitate the discovery of the multiple genetic factors involved in the pathogenesis of AD.

Peripheral neuropathy associated with eosinophilia-myalgia syndrome.

In 1989, the Centers for Disease Control recognized the existence of an epidemic illness characterized by myalgia and eosinophilia in individuals taking preparations containing L-tryptophan. We evaluated 3 patients with eosinophilia-myalgia syndrome who presented with subacute progressive neuropathies. The neuropathies were predominantly motor and maximal in the lower extremities. Two patients were confined to a wheelchair and one was ventilator-dependent and bedridden. Sensory loss predominantly involved small fiber modalities. Electrophysiological studies showed multifocal marked conduction slowing and conduction block indicating segmental demyelination, with associated axonal degeneration that was accentuated distally. Examination of sural nerve biopsy specimens demonstrated axonal degeneration in all 3 patients and perivascular infiltrates in 2. Levels of quinolinic acid, a neurotoxic metabolite of L-tryptophan, were elevated in the cerebrospinal fluid in the 2 patients in whom it was measured. The cause of the neuropathy is unknown but may include immune mechanisms or toxicity of eosinophils, L-tryptophan, its metabolic products, or contaminants within L-tryptophan preparations.

Coma.

The preceding discussion is an attempt to stress anatomy in the diagnosis of coma. By localizing the offending lesion, the physician can apply the appropriate diagnostic and therapeutic measures more adeptly. Because physicians are also frequently asked to prognosticate, I have tried to summarize the work of Plum and Posner in their study of the outcome of patients presenting in coma. The primary care physician is encouraged to plan at least for the basics in case he or she is faced with a comatose patient.