the NINDS TPA Stroke Study GroupBackground and Purpose 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

Objective.-The periaqueductal gray matter (PAG) is at the center of a powerful descending antinociceptive neuronal network. We studied iron homeostasis in the PAG as an indicator of function in patients with episodic migraine (EM) between attacks and patients with chronic daily headache (CDH) during headache. High-resolution magnetic resonance techniques were used to map the transverse relaxation rates R2, R2*, and R2 Ј in the PAG, red nucleus (RN), and substantia nigra (SN). R2 Ј is a measure of non-heme iron in tissues.Methods.-Seventeen patients diagnosed with EM with and without aura, 17 patients diagnosed with CDH and medication overuse, and 17 normal adults (N) were imaged with a 3.0-tesla magnetic resonance imaging system. For each subject, mean values of the relaxation rates, R2 (1/T2), R2* (1/T2*), and R2 Ј (R2* Ϫ R2) were obtained for the PAG, RN, and SN. R2, R2*, and R2 Ј values of the EM, CDH, and N groups were compared using analysis of variance, Student t test, and correlation analysis.Results.-In the PAG, there was a significant increase in mean R2 Ј and R2* values in both the EM and CDH groups ( P Ͻ .05) compared with the N group, but no significant difference in these values was demonstrated between the EM and CDH groups, or between those with migraine with or without aura in the EM group. Positive correlations were found for duration of illness with R2 Ј in the EM and CDH groups. A decrease in mean R2 Ј and R2* values also was observed in the RN and SN of the CDH group compared with the N and EM groups ( P Ͻ .05), explained best by flow activation due to head pain.Conclusions.-Iron homeostasis in the PAG was selectively, persistently, and progressively impaired in the EM and CDH groups, possibly caused by repeated migraine attacks. These results support and emphasize the role of the PAG as a possible "generator" of migraine attacks, potentially by dysfunctional control of the trigeminovascular nociceptive system. Key words: periaqueductal gray matter, iron, transverse relaxation rates Abbreviations: PAG periaqueductal gray matter, MWOA migraine without aura, DRN dorsal raphe nucleus, LC locus ceruleus, R2, R2*, R2 Ј transverse relaxation rates, RN red nucleus, SN substantia nigra, EM episodic migraine, CDH chronic daily headache, MWA migraine with aura, N healthy normal adults, GESFIDE gradient-echo sampling of free induction delay and echo, RF radiofrequency, ISODATA Iterative Self-organizing Data Analysis Technique ( Headache 2001;41:629-637) The midbrain periaqueductal gray matter (PAG) is an anatomically heterogeneous, functionally diverse region of densely layered neurons surrounding the aqueduct of Sylvius.1 Receiving input from the frontal cortex and hypothalamus and projecting to the rostral ventromedial medulla and from there to the medullary and spinal dorsal horn, the PAG is the center of a powerful descending antinociceptive neuronal network.2 Further, the PAG can be consideredFrom the

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Hemorrhagic stroke was more frequent in those treated with atorvastatin, in those with a hemorrhagic stroke as an entry event, in men, and increased with age. Those with Stage 2 hypertension at the last visit prior to the hemorrhagic stroke were also at increased risk. Treatment did not disproportionately affect the hemorrhagic stroke risk associated with these other factors. There were no relationships between hemorrhage risk and baseline low-density lipoprotein (LDL) cholesterol level or recent LDL cholesterol level in treated patients.

We conclude that visually triggered headache and visual change in patients with migraine is accompanied by spreading suppression of initial neuronal activation and increased occipital cortex oxygenation. We postulate that this spreading suppression may be associated with initial activation of a migraine attack, independent of whether there are associated aura symptoms. We further postulate that there may be an association between vasodilation accompanying the initial stage of suppression and the induction of headache.

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Background and Purpose-Studies of cerebral activation of motor function after ischemic stroke may enhance our understanding of the underlying mechanisms of motor functional recovery, including the role of the noninfarcted hemisphere. Methods-Eight right-handed recovering hemiparetic or hemiplegic patients were studied using functional MRI. Results were evaluated for each patient to consider individual variability in original functional organization, neuroanatomy, infarct size and extent, treatment, age, and sex. The results were also pooled as a group for comparison with a control group of eight right-handed normal subjects. Results-In six of eight stroke patients, extended activation in ipsilateral sensorimotor cortex was observed during paretic hand movements. Bilateral activation of the primary sensorimotor cortex was recorded in three of these six patients; ipsilateral activation alone was recorded in the remaining three patients. Only two patients had mild synkinesia. Furthermore, in two male patients, the paretic hand movements activated extended areas of ipsilateral premotor and dorsolateral prefrontal cortex, when compared with normal subjects. In two patients with left frontal infarction, profound activation in the right supramarginal gyrus and in the right premotor cortex was observed during the ipsilateral paretic hand movements. Conclusions-Synkinesia alone cannot explain the extent of ipsilateral activation in primary sensorimotor cortex. The explanation offered for our findings is that preexisting uncrossed motor neural pathways may be accessed or recruited to compensate for damage to the crossed motor pathways after ischemic stroke. (Stroke. 1998;29:112-122.)

on behalf of the SPARCL InvestigatorsBackground and Purpose-The SPARCL trial showed that atorvastatin 80 mg/d reduces the risk of stroke and other cardiovascular events in patients with recent stroke or transient ischemic attack (TIA). We tested the hypothesis that the benefit of treatment varies according to index event stroke subtype. Methods-Subjects with stroke or TIA without known coronary heart disease were randomized to atorvastatin 80 mg/d or placebo. The SPARCL primary end point was fatal or nonfatal stroke. Secondary end points included major cardiovascular events (MCVE; stroke plus major coronary events). Cox regression models testing for an interaction with treatment assignment were used to explore potential differences in efficacy based on stroke subtype. Results-For