E. C. Haley

Improved Reliability of the NIH Stroke Scale Using Video Training

Despite the frequent use of clinical rating scales in multicenter therapeutic stroke trials, no generally acceptable method exists to train and certify investigators to use the instrument consistently. We desired to train investigators to use the National Institutes of Health Stroke Scale in a study of acute stroke therapy so that all examiners rated patients comparably. Methods We devised a two-camera videotape method that optimizes the visual presentation of examination findings. We then measured the effectiveness of the training by asking each investigator to evaluate a set of 11 patients, also on videotape. We tabulated the evaluations, devised a scoring system, and calculated measures of interobserver agreement among the participants in this study. Results We trained and certified 162 investigators. We found moderate to excellent agreement on most Stroke Scale items (unweighted K>0.60). TWO items, facial paresis and ataxia, exhibited poor agreement (unweighted K<0.40) and should be revised in future editions of the scale. Performance improved with video training compared with previous studies. Inclusion of the motor rating of the unaffected limbs in the total score did not affect reliability. Conclusions Video training and certification is a practical and effective method to standardize the use of examination scales. Two cameras must be used during the taping of patients to accurately present the clinical findings. This method is easily adapted to any study in which a large number of investigators will be enrolling patients at multiple clinical centers.

Treatment of right hemispheric cerebral infarction by hemicraniectomy.

An anecdotal series of nine patients (three men and six women with an average age of 57 years) presented with progressive neurologic deterioration while on medical therapy for large right hemispheric cerebral infarction. Clinical signs of uncal herniation (anisocoria or fixed and dilated pupils, and/or left hemiplegia with right decerebrate posturing) were present in seven of these nine patients. Computerized tomography of the head confirmed mass effect from cerebral edema. It was the clinical judgment of the treating neurologists and neurosurgeons that each of these nine patients would perish unless surgical decompression of the infarcted brain was performed. Accordingly, each was treated with right hemicraniectomy and dural augmentation. Six patients demonstrated neurologic improvement on the first postoperative day. One patient, with a postoperative diagnosis of lung cancer, died 1 month after surgery. The remaining eight patients are currently living with their families with a follow-up period ranging from 5 to 25 months. Patient outcome as evaluated by the Barthel Index indicates that three individuals are functioning with minimal assistance and that the remaining six patients are functionally dependent. After rehabilitative therapy, four patients returned for elective cranioplasty. These results suggest that hemicraniectomy can be an effective lifesaving procedure for malignant cerebral edema after large hemispheric infarction.

Pilot randomized trial of tissue plasminogen activator in acute ischemic stroke. The TPA Bridging Study Group.

BACKGROUND AND PURPOSE Early thrombolytic therapy with recombinant tissue-type plasminogen activator is a theoretically attractive approach to the treatment of acute focal cerebral ischemia. In preparation for a larger multicenter trial, three centers piloted a protocol for a randomized, double-blind, placebo-controlled trial of intravenous recombinant tissue-type plasminogen activator begun within 3 hours of the onset of symptoms of acute stroke to test its feasibility and to explore trends. METHODS Eligible patients had pretreatment computed tomographic scanning, gave informed consent, and began treatment with either 0.85 mg/kg recombinant tissue-type plasminogen activator or placebo as soon as possible, but no later than 180 minutes after stroke onset. Patients were stratified by whether treatment was begun within 90 minutes or 91 to 180 minutes from onset. The primary end point was the proportion of patients in each group who improved by 4 or more points on the National Institutes of Health Stroke Scale at 24 hours, as determined by a separate blinded evaluator. RESULTS Twenty-seven patients were randomized: 20 (10 recombinant tissue-type plasminogen activator, 10 placebo) within 90 minutes, and 7 (4 recombinant tissue-type plasminogen activator, 3 placebo) from 91 to 180 minutes. Median baseline Stroke Scale scores were 16 (minimum = 5, maximum = 26) for the recombinant tissue-type plasminogen activator-treated group and 11 (minimum = 3, maximum = 21) for the control subjects in the group treated within 90 minutes. Six patients treated with recombinant tissue-type plasminogen activator within 90 minutes improved by 4 or more points at 24 hours compared with 1 patient in the placebo group (P < .05, Fishers Exact Test). Two patients in each group in the 91- to 180-minute arm improved. One fatal intracerebral hemorrhage occurred in the placebo group. CONCLUSIONS A randomized, double-blind, placebo-controlled trial of recombinant tissue-type plasminogen activator very early in acute stroke is feasible. Preliminary observations suggest that recombinant tissue-type plasminogen activator treatment within 90 minutes may be associated with early neurological improvement. Larger studies are needed so that the potentially serious short-term risks of this treatment can be assessed in relation to meaningful long-term benefit.

Failure of heparin to prevent progression in progressing ischemic infarction.

Anticoagulation with heparin is frequently recommended for patients with progressing ischemic cerebral infarction, yet little data is available detailing the acute results of treatment with this agent. We report the results of continuous intravenous heparin treatment in 36 consecutive patients admitted with progressing ischemic infarction, all of whom had computed tomography scans to exclude the diagnosis of hemorrhage prior to treatment. Overall, 18 of 36 (50%) had continued neurologic worsening despite treatment. The incidence of further worsening was greater in carotid territory infarctions (14 of 19, 74%) than in either vertebrobasilar (2 of 8, 25%) or lacunar (2 of 9, 22%) infarctions (p less than 0.05, Fishers exact test). These observations suggest that additional controlled studies of the efficacy of heparin in progressing ischemic infarction are warranted.

The syndrome of bilateral hemispheric border zone ischemia.

Symptoms compatible with vertebrobasilar ischemia have been reported in patients with unilateral or bilateral carotid occlusive disease. Intracranial steal phenomena have been proposed to explain the symptoms. In a review of 54 patients with angiographically documented severe bilateral carotid stenosis (less than or equal to 2 mm residual lumen) or occlusion, eight had symptoms suggesting vertebrobasilar insufficiency. Five patients were identified retrospectively, and the other three were evaluated prospectively. Symptoms included various combinations of hemodynamically mediated, transient bilateral motor, sensory, or visual impairment. Dysarthria, dysphagia, and diplopia were generally absent. Each patient also described additional symptoms compatible with transient hemispheric or retinal ischemia. The anatomic regions subserving the bilateral vertebrobasilar-like symptoms could be correlated with angiographically estimated arterial border zones in both hemispheres and may thus represent bilateral hemispheric border zone ischemia rather than brain stem ischemia. An intracranial steal need not be invoked.

Strategies for Early Treatment of Acute Cerebral Infarction

For cerebral infarction, potentially effective therapeutic agents include calcium channel antagonists, excitatory amino acid receptor blockers, free radical scavengers, and agents promoting thrombolysis [7], To evaluate these interventions in patients, they must be administered very early after symptom onset, ideally within several hours. The time threshold in humans for irreversible cellular injury following focal cerebral ischemia has not been established. No doubt it will vary depending on the degree of ischemia and its location within the brain. In primates laboratory studies indicate a threshold for neocortex of 3 h or less [9].

Factors Related to Intracranial Hematoma Formation in Patients Receiving t-PA for Acute Ischemic Stroke

Tissue plasminogen activator (rt-PA) is used widely for acute myocardial infarction (MI) in the United States and is currently undergoing clinical trial in acute, ischemic stroke. Both theory and practice have raised concerns about intracranial bleeding induced by rt-PA, so that in the United States, rt-PA is contraindicated in MI patients with a “history of a cerebrovascular accident.” An open-label, Phase I study sponsored by the NIH recently assessed the safety and efficacy of single-chain rt-PA. The trial required hyper-acute treatment, initially within 90 min and subsequently in a 91- to 180-min time window [6]; results of these trials have been published and suggest that rt-PA is relatively safe and may be clinically effective. Nonetheless, complicating intracerebral hematomas did occur, 3 in the 0- to 90-min group of 74 patients and 2 in the 90- to 180- min group of 20 patients. Analysis of the 74 0- to 90-min patients suggested that the risk of intracerebral hematoma increased with increasing rt-PA dose [3], but with merely 3 patients, only limited analyses were possible. Although total numbers are still small, the existence of 5 hematoma patients now permits a more detailed effort to identify risk factors associated with hemorrhage.

Tirilazad and Aneurysmal Subarachnoid Hemorrhage

A randomized double-blind dose-escalation trial of tirilazad mesylate versus placebo was done in patients admitted within 72 hours from SAH. 3 escalating doses of tirilazad were administered (0.6 mg, 2.0 mg, 6.0 mg/kg/day). 245 patients from 12 canadian centers were included in the study: all received concurrent therapy with oral nimodipine, and hypertensive hypervolemic hemodilution therapy as indicated. Out of these patients, 61 received placebo, 51 the 0.6 mg/kg dose, 42 the 2.0 mg/kg dose and 91 the 6.0 mg/kg dose. The group treated with the highest dose presented a significantly higher incidence of thick layers of blood in the subarachnoid space by CT scan.