Transient Neurological Attacks in the General Population : Prevalence, Risk Factors, and Clinical Relevance

The Rotterdam Study is a single-center cohort study of 7983 subjects, aged 55 years or over, who live in the suburb of Ommoord in Rotterdam, the Netherlands. The study includes residents of six homes for the elderly (897 participants). The study was approved by the medical ethics committee of Erasmus University. Written informed consent was obtained from all participants. The rationale and design of the Rotterdam Study have been described elsewhere.⁷ Baseline measurements were collected from March 1990 through July 1993, comprising an extensive home interview, followed by two visits at the Rotterdam Study research center for clinical examinations. Overall response of those invited to participate was 78%.

During the visit at the research center, a trained Rotterdam Study physician asked all participants, “Did you experience a short period with disturbances of sensibility in your face, arms, or legs, which lasted less than 24 hours over the last 3 years?” Similar questions were asked for disturbances in strength, speech, and vision. When answers were positive, time of onset, duration, and disappearance of symptoms and whether a general practitioner had been consulted were recorded. Additionally, a detailed description of the symptoms in ordinary language was obtained.⁸ On the basis of this information, one of the investigators, a neurologist (P.J.K.), classified subjects as typical TIA, nonspecific neurological attacks (atypical TIA), or no TIA.⁹ An attack was regarded as being a typical TIA according to the guidelines of the Ad Hoc Committee for the Classification and Outline of Cerebrovascular Disease⁴ : ie, (1) weakness, clumsiness, or sensory alteration in one or both limbs on the same side, speech or language disturbance, loss of vision in one eye or part of the eye, or homonymous hemianopsia for symptoms that pertain to the carotid territory; (2) weakness or clumsiness (sometimes changing from one side to another), sensory alteration, complete blindness or homonymous hemianopsia, ataxia, imbalance, or unsteadiness not associated with vertigo; and/or (3) two or more of the following: diplopia, dysphagia, dysarthria, or vertigo for symptoms that pertain to the vertebrobasilar territory.¹⁰ The attack was judged nonspecific if the subject had one or more of the following symptoms: disturbances of vision in one or both eyes consisting of flashes, objects, distorted-view tunnel vision, or image moving on change of posture; alteration of muscle strength consisting of tiredness or heavy sensation in one or more limbs, either unilateral or bilateral; sensory symptoms alone (unilateral or bilateral) or a gradual spread of sensory symptoms; brain stem symptoms and coordination difficulties consisting of isolated disorder of swallowing or articulation, double vision, dizziness, or uncoordinated movements; and accompanying symptoms including unconsciousness, limb jerking, tingling of the limbs or lips, disorientation, and amnesia.⁶ A reproducibility study in which 121 case histories were reclassified by the same neurologist, blinded for the initial diagnosis, revealed a weighted κ of 0.77 (P<.05), indicating a good reproducibility.

A second source of information on TIA came from those subjects who had replied affirmatively to the question “Did you ever suffer from a stroke?” Of these subjects, supplementary medical information, such as a copy of the hospital discharge records or a detailed description of the signs and symptoms, was obtained from the general practitioner. On the basis of the available information, these subjects were also classified by the same neurologist as having had a stroke, a (typical/nonspecific) TNA but not a stroke, or neither a TNA nor a stroke. As described elsewhere, 14% of the subjects were classified as having had a TNA but no stroke.¹¹ The two sources were combined in the present analyses. In short, of all subjects with available information on the questions on TNA and stroke, negative answers on both questions were reported by 6830 subjects; 246 reported a stroke but not a TNA; 157 subjects reported no stroke but a TNA; and 70 reported both a stroke and a TNA. Of these 70 subjects, 36 were considered to have a typical TIA, 21 were considered to have had a stroke after the TNA, and 13 were considered to have had a nonspecific TNA.

In the Rotterdam Study, information on health status, medical history, current drug use, and smoking was obtained using a computerized questionnaire, which included a Dutch version of the Rose questionnaire for assessment of prevalent angina pectoris.¹² Determination of a history of myocardial infarction was based on the question “Did you ever suffer from a myocardial infarction for which you were hospitalized?” Diabetes mellitus was considered present when subjects were currently using oral blood sugar–lowering drugs or receiving insulin treatment. With respect to smoking, subjects were categorized into groups of current smokers, former smokers, and those who had never smoked. During two visits at the research center, several cardiovascular risk factors were measured. Height and weight were measured, and body mass index (kilograms per meter squared) was calculated. Sitting blood pressure was measured at the right upper arm using a random-zero sphygmomanometer. The average of two measurements obtained at one occasion, separated by a count of the pulse rate, was used in the present analysis. Hypertension was defined as a systolic blood pressure of 160 mm Hg or higher, a diastolic blood pressure of 95 mm Hg or higher, or current use of antihypertensive drugs for the indication hypertension. Carotid atherosclerosis was assessed using ATL Ultramark IV with a 7.5-MHz linear-array transducer. The common carotid artery and the carotid bifurcation were evaluated on-line for the presence (yes/no) of atherosclerotic lesions on both the near and the far wall of the carotid artery. Atherosclerosis was considered present when one or more plaques were seen during ultrasonography as described elsewhere.¹³ Plaques were defined as a focal widening relative to adjacent segments, with protrusion into the lumen composed of either calcified deposits only or a combination of calcification and noncalcified material. No attempt was made to quantify the size or extent of the lesions or the percentage of stenosis of the carotid arteries. An ECG was made in 6579 subjects, and the presence of a myocardial infarction (Q-wave) and arrhythmia was assessed using an automated diagnostic classification system of the Modular Electrocardiogram Analysis System (MEANS).^{14 15} Because of the limited number of subjects with cardiac arrhythmias, we defined arrhythmia as either atrial flutter (0.2%), atrial fibrillation (2.9%), atrial arrhythmia (0.5%), or atrioventricular arrhythmia (1.0%). A nonfasting venous blood sample was taken as described elsewhere.¹⁶ Serum total cholesterol was determined using an automated enzymatic procedure. HDL cholesterol was measured similarly, after precipitation of the non-HDL fraction with phosphotungstate magnesium.

Subjects of the Rotterdam Study pilot phase were excluded (n=384) because of differences in the questionnaire. No information was available on the TNA symptom questions in the interview of 245 subjects. Complete self-reported information was therefore available for 7354 subjects. Results on prevalence are presented by age and sex. The age on the day of participation (interview) was used in the analysis of prevalence. Logistic regression was applied to study the association between cardiovascular risk factors and both typical TIA and nonspecific TNA. ORs were calculated as measures of strength of the association, and results are expressed with a corresponding 95% CI.