Frequency, risk factors, anatomy, and course of unilateral neglect in an acute stroke cohort.

OBJECTIVE: To delineate the frequency, course, risk factors, and neuroanatomy of hemispatial neglect in a large stroke cohort. METHODS: One thousand two hundred eighty-one patients with acute stroke were enrolled in a multicenter trial of an anticoagulant. Presence and severity of neglect were assessed with the NIH Stroke Scale (NIHSS) neglect item, assessing tactile extinction and visuospatial neglect at entry, daily for 1 week, and at 3 months. Head CT scans were obtained on day 7, and infarct location and size were characterized. RESULTS: Neglect was common at presentation, occurring in 43% of right brain-lesioned (RBL) patients and 20% of left brain-lesioned (LBL) patients (p < 0.001). At 3 months, neglect was present in 17% of RBL patients and in 5% of LBL patients (p < 0.001). In RBL patients, neglect was most frequently associated with lesions involving the (in descending order) temporal, parietal, frontal, occipital lobes, basal ganglia, and thalamus. Neglect was more common and persistent with cortical than with subcortical lesions. Increasing age was associated with increased risk of neglect in RBL patients, whereas gender and handedness did not significantly affect neglect frequency. CONCLUSIONS: This series confirms that hemispatial neglect may occur with damage to several supratentorial structures but is most common and persistent with lesions of the right temporoparietal cortex. Increasing age is associated with neglect, particularly after right brain lesions. Gender and handedness do not exert a marked effect on the likelihood of the occurrence of neglect.

Effect of prior aspirin use on stroke severity in the trial of Org 10172 in acute stroke treatment (TOAST).

BACKGROUND AND PURPOSE: Although the efficacy of aspirin in reducing stroke incidence is clear, its role in reducing stroke severity is disputed. This study compares stroke severity between patients who did or did not take aspirin in the week before stroke and enrollment in the Trial of Org 10172 in Acute Stroke Treatment (TOAST). METHODS: Of 1275 patients randomized, 509 reported aspirin use in the week before stroke; 766 did not. Clinical stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS) and the Supplementary Motor Examination (SME) at trial entry and at 3 months. Using these scales, we compared the categorization of stroke severity (mild, moderate, and severe) and mean scores between aspirin users and nonusers. RESULTS: The difference in distribution of baseline NIHSS scores was statistically significant between aspirin users and nonusers (P=0.006), with a greater percentage of milder strokes among aspirin users. The difference in mean baseline NIHSS scores was also significantly lower in aspirin users (8.2) and nonusers (9.3) (P=0.003). The distribution of baseline SME scores and mean SME scores also showed lower stroke severity in aspirin users than in nonusers (P=0.048 and P=0.004, respectively). At 3 months, differences in stroke severity measured by the SME but not the NIHSS remained statistically significant. Seven-day and 3-month mortality did not differ significantly. CONCLUSIONS: In this study aspirin use is associated with milder clinical deficits at stroke onset. These deficits may affect prognosis and influence response to treatment. Future clinical trials should ensure that prestroke aspirin use is comparable in study groups.

Ensuring reliability of outcome measures in multicenter clinical trials of treatments for acute ischemic stroke. The program developed for the Trial of Org 10172 in Acute Stroke Treatment (TOAST).

BACKGROUND AND PURPOSE: Ensuring the reliability and validity of outcome measures used in clinical trials is essential to the success of the trial. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) is a multicenter clinical trial that is recruiting patients with acute ischemic stroke seen at medical centers across the United States. METHODS: This paper describes an approach to train physicians to use three clinical measures: the National Institutes of Health (NIH) Stroke Scale, a supplemental motor examination, and the Glasgow Outcome Scale. The program included education, certification, remediation when needed, monitoring, and reliability assessment. The goal was to ensure that interrater assessments were as equivalent to one another as possible. RESULTS: Of the first 95 clinicians who began the certification process, 75 passed during the first evaluation. Eighteen of the other physicians were able to complete the process after remediation. The intraclass correlations of both the NIH Stroke Scale and supplemental motor examination exceeded 0.95. The kappa values for the Glasgow Outcome Scale were 0.61 and 0.62 for the first and second ratings of the videotape, respectively. CONCLUSIONS: Our experience suggests that a program that includes educational and certification processes can be performed as part of the design of a multicenter clinical trial. The method of providing educational and testing videotapes to each site so that physicians can be trained and certified is an effective, inexpensive, and practical approach for enhancing and certifying the expertise of the large number of physicians involved in a multicenter study.

Monitoring therapeutic efficacy of decompressive craniotomy in space occupying cerebellar infarcts using brain-stem auditory evoked potentials.

Brain-stem auditory evoked potentials (BAEPs) have been used to gauge effects of brain-stem dysfunction in humans and animal models. The purpose of this study was to evaluate the usefulness of BAEP in monitoring patients undergoing decompressive surgery of the posterior fossa for space occupying cerebellar infarcts. We report on serial BAEP recordings in 11 comatose patients with space occupying cerebellar infarcts undergoing decompressive craniotomy. BAEP studies were performed within 12 h after admission, 24 h following surgery and prior to extubation. BAEP signals were analyzed using latency determination and cross-correlation. Following surgery, 9 patients regained consciousness; 2 patients persisted in a comatose state and died subsequently. BAEP interpeak latency (IPL) I-V assessed prior to surgery exceeded normal values in all patients in whom it could be reliably measured (N = 9). Following decompressive surgery BAEP wave I-V IPL normalized in 5 patients, but remained prolonged despite dramatic clinical improvement in 4 patients. We prospectively computed the coefficient of cross-correlation (MCC) of combined ipsilateral BAEP trials after right and left ear stimulation. In all patients increasing MCC was associated with clinical improvement. Unchanging or decreasing MCC indicated poor outcome. We conclude that serial BAEP studies are an appropriate perioperative monitoring modality in patients with space occupying cerebellar infarcts undergoing decompressive surgery of the posterior fossa. Our study suggests advantages of cross-correlation analysis as an objective signal processing strategy; relevant information can be extracted even if BAEP wave discrimination is impossible due to severe brain-stem dysfunction.

Calcium antagonists in the management of patients with aneurysmal subarachnoid hemorrhage: a review.

Cerebral arterial vasospasm and infarction is the leading cause of death and disability among patients who reach a major medical center after aneurysmal subarachnoid hemorrhage (SAH). Recent evidence suggests that two calcium antagonists, nimodipine or nicardipine, may be useful in preventing this important complication of SAH. This paper reviews the current status of these two calcium antagonists in the management of SAH.

Large-dose infusions of heparinoid ORG 10172 in ischemic stroke.

We evaluated the safety and possible efficacy of large doses of the heparinoid ORG 10172 in 57 patients with acute or progressing ischemic stroke. Patients received a loading bolus of the drug followed by a maintenance intravenous infusion for 7 days. The plasma level of ORG 10172 was monitored by the degree of inhibition of coagulation factor Xa. In general, the drug was well tolerated and few hemorrhagic complications occurred. Two patients with large cardioembolic hemispheric strokes had intracranial hemorrhagic complications. Most patients improved during treatment. By 3 months after the stroke, 37 patients (65%) had a favorable outcome (minimal or no residual disability). This study suggests that high-dose intravenous infusions of ORG 10172 can be safely given to patients with acute ischemic stroke.

Nicardipine HCl: clinical experience in patients undergoing anaesthesia for intracranial aneurysm clipping.

Previous studies have reported haemodynamic interactions between dihydropyridine calcium antagonists and general anaesthesia. During anaesthesia for intracranial aneurysm surgery, we prospectively compared haemodynamic values obtained from 13 patients being treated with nicardipine HCl (0.15 mg.kg-1.hr-1 IV) for cerebral vasospasm against values obtained from 11 untreated controls. Prior to induction of anaesthesia, nicardipine-treated patients had significantly elevated mean +/- SD cardiac index (5.67 +/- 1.30 vs 3.99 +/- 0.73 L.min-1.m-2) while MAP (86 +/- 10 vs 99 +/- 14 mmHg) and systemic vascular resistance (647 +/- 227 vs 1141 +/- 404 dynes.sec-1.cm-5) were reduced. Heart rate, CVP, and PACWP were similar between groups. Anaesthesia induction and tracheal intubation resulted in similar haemodynamic values between groups with the exception of CVP (10 +/- 5 vs 5 +/- 2 mmHg) and PACWP (15 +/- 5 vs 8 +/- 3 mmHg) which were elevated in the nicardipine group (P less than 0.01). Mannitol infusion and deliberate hypotension resulted in nearly identical haemodynamic responses in both groups. Nicardipine-treated patients required more intravenous fluids during the operative procedure (2.4 +/- 0.3 L vs 1.5 +/- 0.4 L, P less than 0.05) and were less likely to require isoflurane supplementation to morphine sulphate/nitrous oxide anaesthesia (P less than 0.01). In summary, our experience with nicardipine HCl revealed no major untoward effects with respect to maintenance of intraoperative haemodynamic stability despite continuous antivasospasm therapy with this vasodilator.

Dose-escalation study of intravenous nicardipine in patients with aneurysmal subarachnoid hemorrhage.

A dose-escalation study of the calcium ion entry blocking drug nicardipine was performed using large dose infusions in 67 patients with recent aneurysmal subarachnoid hemorrhage (SAH). A safe, potentially therapeutic dose of the drug was determined. Patients admitted within 7 days of SAH from a documented cerebral aneurysm were entered into the study if no spasm was present on the initial angiogram. Nicardipine was administered as a continuous intravenous infusion throughout the 14-day period after SAH, regardless of the timing of surgery. To determine the safest possible dose, nicardipine was administered at seven dose levels from 0.01 to 0.15 mg/kg/hr. The total daily doses ranged from 27.7 mg to 375.0 mg. A follow-up angiogram was carried out on all 67 patients 7 to 10 days after SAH. Computerized tomography and neurological examinations were used to determine the presence of cerebral infarction. No major adverse effects, unexpected reactions, or permanent sequelae could be attributed to nicardipine. A decline in blood pressure was noted following administration of the drug. This occurred more frequently among patients given the largest dose but did not produce clinical problems or require discontinuation of the drug. Favorable outcomes were noted in 52 patients (78%). Vasospasm was found by arteriography in 31 patients (46%). A dose-related trend was noted: only eight (24%) of 33 patients treated at the highest dose level (approximately 10 mg/hr) developed arteriographic evidence of vasospasm. Symptomatic vasospasm was diagnosed in only two (6%) of 33 patients treated with this dose. Of the 34 patients receiving the lower dose levels, angiographic spasm was observed in 68% and symptomatic vasospasm in 27%. No deaths due to vasospasm occurred. Nicardipine appears to prevent both vasospasm and cerebral ischemia after SAH. A multicenter randomized double-blind trial to test this hypothesis is planned.

Syndrome of the paramedian thalamic arteries: clinical and neuroimaging correlation.

Two patients had sudden alteration of consciousness followed by fluctuating hypersomnia and bilateral ophthalmoplegia. Magnetic resonance imaging showed asymmetric, paramedian thalamic and midbrain lesions. The clinical and neuroimaging features are consistent with the syndrome of the paramedian thalamic arteries of the basilar communicating artery. These strokes were caused by an embolus to the rostral basilar artery originating from a fibrillating heart. Magnetic resonance imaging clearly delineates the delicate pattern of arterial involvement in mesodiencephalic junction infarctions.

Unruptured fusiform aneurysms of the posterior circulation with thalamic infarction.

Three patients with unruptured fusiform aneurysms of the posterior circulation presented with nonhemorrhagic thalamic infarctions. All of the aneurysms were seen on enhanced computed tomographic (CT) scans preangiographically. Although unruptured fusiform aneurysms are probably a rare cause of nonhemorrhagic thalamic infarction, their importance lies in the therapeutic implications of this diagnosis. In patients with nonhemorrhagic thalamic infarction, we suggest careful scrutiny of the blood vessels on enhanced CT scans.

Topographic analysis of somatosensory evoked potentials in patients with well-localized thalamic infarctions.

After stimulation of the median nerve, three major negative peaks (NI, NII and NIII) of somatosensory evoked potentials (SEP) have different latencies along the longitudinal array of scalp electrodes: NI and NII at frontal electrodes have the shortest latency (N17, N29). There is a progressive delay toward the central (N19, N32) and parietal areas (N20, N34). NIII (N60) latency differs from one electrode to another but without consistent anterior-posterior latency shift. A variety of SEP abnormalities was observed in 17 patients with non-hemorrhagic thalamic lesions reflecting a disturbance of the complex intra-thalamic and afferent and efferent thalamic pathways. When the lesions were classified into 5 groups according to the presumed vascular territories involved, there were general but not specific characteristics of SEP abnormalities in each group of patients. In four patients with lesions involving primary sensory nuclei and presenting with the thalamic syndrome or the loss of all modalities of sensation, all SEP components after P14 were absent when the affected arm was stimulated. NI peaks were intact in two patients with thalamic sensory lacunes but NII was delayed. NI was present but delayed in three patients with anterior thalamic lesions not involving primary sensory nuclei. In patients with medial thalamic lesions, delayed central NIII was a common finding. In patients with posterior capsule or lateral thalamus lesions either NII and NIII or NIII alone were affected. NI was also affected in some with sparing of the frontal component (N17). These complex relationships between the types of SEP abnormalities and thalamic lesions are compatible with the presence of multiple, at least partially independent, thalamic generators and thalamocortical projection systems mediating regionally specific SEP components.