Ferdinando S. Buonanno

Visual mental imagery activates topographically organized visual cortex: Pet investigations

Cerebral blood flow was measured using positron emission tomography (PET) in three experiments while subjects performed mental imagery or analogous perceptual tasks. In Experiment 1, the subjects either visualized letters in grids and decided whether an X mark would have fallen on each letter if it were actually in the grid, or they saw letters in grids and decided whether an X mark fell on each letter. A region identified as part of area 17 by the Talairach and Tournoux (1988) atlas, in addition to other areas involved in vision, was activated more in the mental imagery task than in the perception task. In Experiment 2, the identical stimuli were presented in imagery and baseline conditions, but subjects were asked to form images only in the imagery condition; the portion of area 17 that was more active in the imagery condition of Experiment 1 was also more activated in imagery than in the baseline condition, as was part of area 18. Subjects also were tested with degraded perceptual stimuli, which caused visual cortex to be activated to the same degree in imagery and perception. In both Experiments 1 and 2, however, imagery selectively activated the extreme anterior part of what was identified as area 17, which is inconsistent with the relatively small size of the imaged stimuli. These results, then, suggest that imagery may have activated another region just anterior to area 17. In Experiment 3, subjects were instructed to close their eyes and evaluate visual mental images of upper case letters that were formed at a small size or large size. The small mental images engendered more activation in the posterior portion of visual cortex, and the large mental images engendered more activation in anterior portions of visual cortex. This finding is strong evidence that imagery activates topographically mapped cortex. The activated regions were also consistent with their being localized in area 17. Finally, additional results were consistent with the existence of two types of imagery, one that rests on allocating attention to form a pattern and one that rests on activating stored visual memories.

Posterior leukoencephalopathy without severe hypertension: Utility of diffusion-weighted MRI

Objective: Standard MRI confirms the diagnosis of posterior leukoencephalopathy syndrome (PLES), recently associated with an increasing number of medical conditions. In PLES, T2-weighted MRI demonstrates hyperintensity spreading out from posterior brain regions; the pathophysiology remains mysterious. In the acute setting, diffusion-weighted imaging (DWI), but not standard MR imaging, can distinguish ischemic injury from those conditions known to cause vasogenic brain edema. DWI is potentially valuable in understanding the pathophysiology of PLES and in diagnosing patients who do not have previously known risk factors. Methods: Serial CT and MRI studies (including DWI, apparent diffusion coefficient [ADC] maps, and, in one instance, perfusion-weighted imaging) were performed in three female patients with a neurologic syndrome consistent with PLES while hospitalized for treatment of other conditions. Results: None of the patients had previously described risk factors for PLES; all had only mild elevations in blood pressure. MRI showed large, abnormal, T2 hyperintense regions in the posterior cerebrum with corresponding hyperintensity on ADC maps-signal characteristics predominantly consistent with vasogenic edema. There were also smaller patchy posterior cortical regions with decreased ADC and bright DWI consistent with infarction in one, and dramatic conversion of a large region to an ischemic pattern in another. Conclusions: ADC maps and DWI can successfully differentiate PLES from early cerebral ischemia, thus playing a pivotal role in treatment decisions. PLES is associated with a wider variety of conditions than has been previously reported and is not always reversible. Hyperintense DWI signal in patients with the syndrome likely marks a tissue stage of permanent brain injury.

One-year outcome after decompressive surgery for massive nondominant hemispheric infarction.

OBJECTIVE Massive cerebral infarction is often accompanied by early death secondary to transtentorial herniation. We have tested the hypothesis that decompressive hemicraniectomy for massive nondominant cerebral infarction is lifesaving in a series of 14 patients presenting with right hemispheric infarction and clinical signs of uncal herniation and impending death. We have further analyzed, in prospective follow-up examinations, the levels of physical, psychiatric, and social disabilities in these patients. METHODS The methods used included retrospective analysis to determine rates of immediate mortality and morbidity after surgical intervention. Prospective follow-up data were obtained to determine the level of recovery in surviving patients after 1 year. Standardized measures of outcome to assess physical, psychiatric, and social recovery included the Barthel Index, Zung Depression Scale, and Reintegration to Normal Living Index. RESULTS With decompressive hemicraniectomy, we were able to prevent death secondary to transtentorial herniation in all cases; 11 patients experienced long-term survival after the procedure, and three deaths were related to non-neurological causes. We observed that 8 of the 11 surviving patients were at home, were functioning with minimal to moderate assistance, and had Barthel scores greater than 60. The remaining three patients were severely disabled. Seven of the 11 survivors were able to walk at 1 year after undergoing the procedure. Depression and failure to reintegrate socially were experienced by most patients. CONCLUSION This series confirms the lifesaving nature of hemicraniectomy in patients deteriorating because of cerebral edema after infarction. In patients younger than 50 years, recovery to a state of near-independence is possible.

Regional Ischemia and Ischemic Injury in Patients With Acute Middle Cerebral Artery Stroke as Defined by Early Diffusion-Weighted and Perfusion-Weighted MRI

BACKGROUND AND PURPOSE We sought to map early regional ischemia and infarction in patients with middle cerebral artery (MCA) stroke and compare them with final infarct size using advanced MRI techniques. MRI can now delineate very early infarction by diffusion-weighted imaging (DWI) and abnormal tissue perfusion by perfusion-weighted imaging (PWI). METHODS Seventeen patients seen within 12 hours of onset of MCA stroke had MR angiography, standard MRI, and PWI and DWI MRI. PWI maps were generated by analysis of the passage of intravenous contrast bolus through the brain. Cerebral blood volume (CBV) was determined after quantitative analysis of PWI data. Volumes of the initial DWI and PWI lesion were calculated and compared with a final infarct volume from a follow-up imaging study (CT scan or MRI). RESULTS Group 1 (10 patients) had MCA stem (M1) occlusion by MR angiography. DWI lesion volumes were smaller than the volumes of CBV abnormality. In 7 patients the final stroke volume was larger or the same, and in 3 it was smaller than the initial CBV lesion. Group 2 (7 patients) had an open M1 on MR angiography with distal MCA stroke. In 6 group 2 patients, the initial DWI lesion matched the initial CBV abnormality and the final infarct. CONCLUSIONS Most patients with M1 occlusion showed progression of infarction into the region of abnormal perfusion. In contrast, patients with open M1 had strokes consistent with distal branch occlusion and had maximal extent of injury on DWI at initial presentation. Application of these MRI techniques should improve definition of different acute stroke syndromes and facilitate clinical decision making.

Predicting tissue outcome in acute human cerebral ischemia using combined diffusion- and perfusion-weighted MR imaging

Background and Purpose— Tissue signatures from acute MR imaging of the brain may be able to categorize physiological status and thereby assist clinical decision making. We designed and analyzed statistical algorithms to evaluate the risk of infarction for each voxel of tissue using acute human functional MRI. Methods— Diffusion-weighted MR images (DWI) and perfusion-weighted MR images (PWI) from acute stroke patients scanned within 12 hours of symptom onset were retrospectively studied and used to develop thresholding and generalized linear model (GLM) algorithms predicting tissue outcome as determined by follow-up MRI. The performances of the algorithms were evaluated for each patient by using receiver operating characteristic curves. Results— At their optimal operating points, thresholding algorithms combining DWI and PWI provided 66% sensitivity and 83% specificity, and GLM algorithms combining DWI and PWI predicted with 66% sensitivity and 84% specificity voxels that proceeded to infarct. Thresholding algorithms that combined DWI and PWI provided significant improvement to algorithms that utilized DWI alone (P =0.02) but no significant improvement over algorithms utilizing PWI alone (P =0.21). GLM algorithms that combined DWI and PWI showed significant improvement over algorithms that used only DWI (P =0.02) or PWI (P =0.04). The performances of thresholding and GLM algorithms were comparable (P >0.2). Conclusions— Algorithms that combine acute DWI and PWI can assess the risk of infarction with higher specificity and sensitivity than algorithms that use DWI or PWI individually. Methods for quantitatively assessing the risk of infarction on a voxel-by-voxel basis show promise as techniques for investigating the natural spatial evolution of ischemic damage in humans.

CT angiography in the rapid triage of patients with hyperacute stroke to intraarterial thrombolysis: accuracy in the detection of large vessel thrombus.

Purpose The purpose of this work was to evaluate the accuracy of CT angiography (CTA) for the detection of large vessel intracranial thrombus in clinically suspected hyperacute (<6 h) stroke patients. Method Forty-four consecutive intraarterial thrombolysis candidates underwent noncontrast CT followed immediately by CTA. Axial source and two-dimensional collapsed maximum intensity projection reformatted CTA images were rated for the presence or absence of large vessel occlusion. Five hundred seventy-two circle-of-Willis vessels were reviewed; arteriographic correlation was available for 224 of these. Results Sensitivity and specificity for the detection of large vessel occlusion were 98.4 and 98.1%; accuracy, calculated using receiver operating characteristic analysis, was 99%. Mean time for acquisition, reconstruction, and analysis of CTA images was approximately 15 min. Conclusion CTA is highly accurate for the detection and exclusion of large vessel intracranial occlusion and may therefore be valuable in the rapid triage of hyperacute stroke patients to intraarterial thrombolytic treatment.

Normal diffusion-weighted MRI during stroke-like deficits

Background: Diffusion-weighted MRI (DWI) represents a major advance in the early diagnosis of acute ischemic stroke. When abnormal in patients with stroke-like deficit, DWI usually establishes the presence and location of ischemic brain injury. However, this is not always the case. Objective: To investigate patients with stroke-like deficits occurring without DWI abnormalities in brain regions clinically suspected to be responsible. Methods: We identified 27 of 782 consecutive patients scanned when stroke-like neurologic deficits were still present and who had normal DWI in the brain region(s) clinically implicated. Based on all the clinical and radiologic data, we attempted to arrive at a pathophysiologic diagnosis in each. Results: Best final diagnosis was a stroke mimic in 37% and a cerebral ischemic event in 63%. Stroke mimics (10 patients) included migraine, seizures, functional disorder, transient global amnesia, and brain tumor. The remaining patients were considered to have had cerebral ischemic events: lacunar syndrome (7 patients; 3 with infarcts demonstrated subsequently) and hemispheric cortical syndrome (10 patients; 5 with TIA, 2 with prolonged reversible deficits, 3 with infarction on follow-up imaging). In each of the latter three patients, the regions destined to infarct showed decreased perfusion on the initial hemodynamically weighted MRI (HWI). Conclusions: Normal DWI in patients with stroke-like deficits should stimulate a search for nonischemic cause of symptoms. However, more than one-half of such patients have an ischemic cause as the best clinical diagnosis. Small brainstem lacunar infarctions may escape detection. Concomitant HWI can identify some patients with brain ischemia that is symptomatic but not yet to the stage of causing DWI abnormality.

Fever in subarachnoid hemorrhage: Relationship to vasospasm and outcome

Objective: To investigate the causes of fever in subarachnoid hemorrhage (SAH) and examine its relationship to outcome. Background: Fever adversely affects outcome in stroke. Patients with SAH are at risk for cerebral ischemia due to vasospasm (VSP). In these patients, fever may be both caused by, and potentiate, VSP-mediated brain injury. Methods: The authors prospectively studied patients admitted to a neurologic intensive care unit with nontraumatic SAH, documenting Hunt–Hess grade, Fisher group, Glasgow Coma Score, bacterial culture data, daily transcranial Doppler mean velocities, and maximum daily temperatures. Patients were classified as febrile (temperature above 38.3 °C for at least 2 consecutive days) or afebrile (no fever or isolated episodes of temperature above 38.3 °C). VSP was verified by either transcranial Doppler or angiographic criteria. Rankin scale scores on discharge were dichotomized into good (0 to 2) or poor (3 to 6) outcomes. Results: Ninety-two consecutive patients were studied. Thirty-eight patients were classified as febrile. No source for infection was found in 10 of 38 (26%) patients. In a multivariate analysis, three variables independently predicted fever occurrence: ventriculostomy (OR, 8.5 [CI, 2.4 to 29.7]), symptomatic VSP (OR, 5.0 [CI, 1.03 to 24.5]), and older age (OR, 1.75 per 10 years [CI, 1.02 to 3.0]). Poor outcome was related to fever (OR, 1.4 per each day febrile [CI, 1.1 to 1.88]), older age (OR, 1.64 per 10 years [CI, 1.04 to 2.58]), and intubation (OR, 21.8 [CI, 5.6 to 84.5]). Conclusion: Fever in SAH is associated with vasospasm and poor outcome independently of hemorrhage severity or presence of infection.

A Pilot Study of Normobaric Oxygen Therapy in Acute Ischemic Stroke

Background and Purpose— Therapies that transiently prevent ischemic neuronal death can potentially extend therapeutic time windows for stroke thrombolysis. We conducted a pilot study to investigate the effects of high-flow oxygen in acute ischemic stroke. Methods— We randomized patients with acute stroke (<12 hours) and perfusion-diffusion “mismatch” on magnetic resonance imaging (MRI) to high-flow oxygen therapy via facemask for 8 hours (n=9) or room air (controls, n=7). Stroke scale scores and MRI scans were obtained at baseline, 4 hours, 24 hours, 1 week, and 3 months. Clinical deficits and MR abnormalities were compared between groups. Results— Stroke scale scores were similar at baseline, tended to improve at 4 hours (during therapy) and 1 week, and significantly improved at 24 hours in hyperoxia-treated patients. There was no significant difference at 3 months. Mean (±SD) relative diffusion MRI lesion volumes were significantly reduced in hyperoxia-treated patients at 4 hours (87.8±22% versus 149.1±41%; P=0.004) but not subsequent time points. The percentage of MRI voxels improving from baseline “ischemic” to 4-hour “non-ischemic” values tended to be higher in hyperoxia-treated patients. Cerebral blood volume and blood flow within ischemic regions improved with hyperoxia. These “during-therapy” benefits occurred without arterial recanalization. By 24 hours, MRI showed reperfusion and asymptomatic petechial hemorrhages in 50% of hyperoxia-treated patients versus 17% of controls (P=0.6). Conclusions— High-flow oxygen therapy is associated with a transient improvement of clinical deficits and MRI abnormalities in select patients with acute ischemic stroke. Further studies are warranted to investigate the safety and efficacy of hyperoxia as a stroke therapy.

Pharmacological Elevation of Blood Pressure in Acute Stroke Clinical Effects and Safety

BACKGROUND AND PURPOSE Lowering of blood pressure can adversely affect ischemic symptoms in acute stroke. The aim of our study was to determine whether induced hypertension in stroke is safe and to examine its effects on neurological deficits in patients presenting with acute cerebral ischemia. METHODS We retrospectively reviewed all patients admitted to our neurological intensive care unit with the diagnosis of ischemic stroke over a 2.5-year period. Thirty-three patients were not given a pressor agent (Ph- group), while 30 were treated with phenylephrine (Ph+ group) in an attempt to improve cerebral perfusion. RESULTS Baseline characteristics showed few differences between the Ph+ and Ph- groups. Intracerebral hemorrhage, brain edema, cardiac morbidity, and mortality were not increased in the Ph+ group. In 10 of 30 Ph+ patients, a systolic blood pressure threshold was identified below which ischemic deficits worsened and above which deficits improved. The mean threshold was 156 mm Hg (range, 120 to 190 mm Hg). The mean number of stenotic/occluded cerebral arteries was greater in those Ph+ patients with an identified clinical blood pressure threshold (mean, 2.1 per patient) than in Ph+ patients without a threshold (mean, 1.2 per patient; P < .05). CONCLUSIONS The results suggest that careful use of phenylephrine induced hypertension is not associated with an increase in morbidity or mortality in acute stroke. Although based on a retrospective analysis of clinical practice, this report suggests that a subset of patients, particularly those with multiple stenosis of cerebral arteries, may improve neurologically upon elevation of the blood pressure.