Jonathan T. Kleinman

Restoring Cerebral Blood Flow Reveals Neural Regions Critical for Naming

We identified areas of the brain that are critical for naming pictures of objects, using a new methodology for testing which components of a network of brain regions are essential for that task. We identified areas of hypoperfusion and structural damage with magnetic resonance perfusion- and diffusion-weighted imaging immediately after stroke in 87 individuals with impaired picture naming. These individuals were reimaged after 3–5 d, after a subset of patients underwent intervention to restore normal blood flow, to determine areas of the brain that had reperfused. We identified brain regions in which reperfusion was associated with improvement in picture naming. Restored blood flow to left posterior middle temporal/fusiform gyrus, Brocas area, and/or Wernickes area accounted for most acute improvement after stroke. Results show that identifying areas of reperfusion that are associated with acute improvement of a function can reveal the brain regions essential for that function.

Neural substrates of visuospatial processing in distinct reference frames: Evidence from unilateral spatial neglect

There is evidence for different levels of visuospatial processing with their own frames of reference: viewer-centered, stimulus-centered, and object-centered. The neural locus of these levels can be explored by examining lesion location in subjects with unilateral spatial neglect (USN) manifest in these reference frames. Most studies regarding the neural locus of USN have treated it as a homogenous syndrome, resulting in conflicting results. In order to further explore the neural locus of visuospatial processes differentiated by frame of reference, we presented a battery of tests to 171 subjects within 48 hr after right supratentorial ischemic stroke before possible structural and/or functional reorganization. The battery included MR perfusion weighted imaging (which shows hypoperfused regions that may be dysfunctional), diffusion weighted imaging (which reveals areas of infarct or dense ischemia shortly after stroke onset), and tests designed to disambiguate between various types of neglect. Results were consistent with a dorsal/ventral stream distinction in egocentric/allocentric processing. We provide evidence that portions of the dorsal stream of visual processing, including the right supramarginal gyrus, are involved in spatial encoding in egocentric coordinates, whereas parts of the ventral stream (including the posterior inferior temporal gyrus) are involved in allocentric encoding.

Neural regions essential for reading and spelling of words and pseudowords

To identify dysfunctional brain regions critical for impaired reading/spelling of words/pseudowords by evaluating acute stroke patients on lexical tests and magnetic resonance imaging, before recovery or reorganization of structure–function relationships.

Speech and language functions that require a functioning Broca's area

A number of previous studies have indicated that Brocas area has an important role in understanding and producing syntactically complex sentences and other language functions. If Brocas area is critical for these functions, then either infarction of Brocas area or temporary hypoperfusion within this region should cause impairment of these functions, at least while the neural tissue is dysfunctional. The opportunity to identify the language functions that depend on Brocas area in a particular individual was provided by a patient with hyperacute stroke who showed selective hypoperfusion, with minimal infarct, in Brocas area, and acutely impaired production of grammatical sentences, comprehension of semantically reversible (but not non-reversible) sentences, spelling, and motor planning of speech articulation. When blood flow was restored to Brocas area, as demonstrated by repeat perfusion weighted imaging, he showed immediate recovery of these language functions. The identification of language functions that were impaired when Brocas area was dysfunctional (due to low blood flow) and recovered when Brocas area was functional again, provides evidence for the critical role of Brocas area in these language functions, at least in this individual.

Unilateral neglect is more severe and common in older patients with right hemispheric stroke

Introduction: Unilateral neglect after acute right hemispheric stroke significantly impedes poststroke recovery. We studied patients with right hemispheric stroke to determine whether increasing age was associated with more frequent or more severe neglect. Methods: Eight neglect tests within 5 days of symptom onset (and within 24 hours of admission) were administered to 204 subjects with acute right hemispheric stroke. Size of infarct was measured, and neglect tests were scored as percent error. “Any neglect” was defined by an elevated neglect test score, standardized relative to a group of normal controls. Results: When tested for neglect soon after acute stroke admission, 69.6% of subjects older than 65 years had “any neglect” (defined by comparison to a group of normal controls), compared with 49.4% of subjects aged 65 years and younger (p = 0.008). For every additional 10 years of age, patients were 1.83 times as likely to have neglect, even after adjusting for diffusion-weighted imaging (DWI) infarct volume and NIH Stroke Scale (NIHSS) score (95% CI 1.38–2.43). In addition, DWI volume and NIHSS independently predicted neglect. Score on virtually all of the neglect tests worsened as an effect of age. Percentage error on a line cancellation task was 3.8% higher for every additional 10 years of age, after adjustment for DWI volume and NIHSS (p = 0.006). Similar results were found for other neglect tests. Conclusions: Increasing age in patients with acute right hemispheric stroke significantly increases the odds of unilateral neglect as well as severity of neglect, independently of size of the stroke or NIH Stroke Scale score. The reason for this finding in older patients may be because they have more brain atrophy and may be less able to compensate for cerebral infarction, or because they tend to have more cardioembolic strokes, which may be more cortically based.

Crossed cerebellar diaschisis in acute stroke detected by dynamic susceptibility contrast MR perfusion imaging.

BACKGROUND AND PURPOSE: Crossed cerebellar diaschisis (CCD), the decrease in blood flow and metabolism in the cerebellar hemisphere contralateral to a supratentorial stroke, is frequently reported on positron-emission tomography (PET) and single-photon emission CT (SPECT) but is rarely described with MR perfusion techniques. This study was undertaken to determine the frequency of CCD observed in acute stroke by retrospective review of a research data base of patients with acute stroke evaluated by diffusion-weighted (DWI) and dynamic contrast susceptibility perfusion MR imaging (PWI). MATERIALS AND METHODS: PWI scans of 301 consecutive patients with acute stroke and positive DWI abnormality from a research data base were reviewed. Contralateral cerebellar hypoperfusion was identified by inspection of time-to-peak (TTP) maps for asymmetry with an absence of cerebellar abnormalities on T2-weighted scans, DWI, or disease of the vertebrobasilar system on MR angiography. In a subset of the cases, quantitative analysis of perfusion scans was performed using an arterial input function and singular value decomposition (SVD) to generate cerebral blood flow (CBF) maps. RESULTS: A total of 47 of 301 cases (15.61%) met the criteria of CCD by asymmetry of cerebellar perfusion on TTP maps. On quantitative analysis, there was corresponding reduction of CBF by 22.75 ± 10.94% (range, 7.45% to 52.13%) of the unaffected cerebellar hemisphere). CONCLUSIONS: MR perfusion techniques can be used to detect CCD, though the frequency presented in this series is lower than that commonly reported in the PET/SPECT literature. Nevertheless, with its role in acute stroke and noninvasive nature, MR perfusion may be a viable alternative to PET or SPECT to study the phenomenon and clinical consequences of supratentorial stroke with CCD.

Intracerebral Hemorrhage Volume Predicts Poor Neurologic Outcome in Children

BACKGROUND AND PURPOSE Although intracerebral hemorrhage (ICH) volume and location are important predictors of outcome in adults, few data exist in children. METHODS A consecutive cohort of children, including full-term newborns to those younger than 18 years of age with nontraumatic, acute ICH and head CT available for analysis were studied. Clinical information was abstracted via chart review. Hemorrhage volume was expressed as percentage of total brain volume (TBV) with large hemorrhage defined as >or=4% of TBV. Hemorrhages were manually traced on each head CT slice and volumes were calculated by multiplying by slice thickness. Location was classified as supratentorial or infratentorial. Logistic regression was used to identify predictors of poor neurological outcome, defined as a Glasgow outcome scale <or=2 (death or persistent vegetative state). RESULTS Thirty children were included, median age 6 years. Median ICH volume was 20.4 cm(3) and median ICH size as a percentage of TBV was 1.9%. Only 4 of 22 children with ICH <4% of TBV had poor outcomes, vs 5 of 8 children with ICH >or=4% of TBV (P=0.03). In multivariate analysis, hemorrhage >or=4% of TBV (OR, 22.5; 95% CI, 1.4-354; P=0.03) independently predicted poor outcome 30 days after ICH. In this small sample, infratentorial hemorrhage location and the presence of intraventricular hemorrhage did not predict poor outcome. CONCLUSIONS ICH volume predicts neurological outcome at 30 days in children, with worst outcome when hemorrhage is >or=4% of TBV. Location and ICH etiology may also be important. These findings identify children with ICH who are candidates for aggressive management and may influence counseling regarding prognosis.

Supratentorial Regions of Acute Ischemia Associated With Clinically Important Swallowing Disorders. A Pilot Study

Background and Purpose— Dysphagia is a common problem after stroke associated with significant morbidity and mortality. Except for patients with brain stem strokes, particularly lateral medullary strokes, it is difficult to predict which cases are likely to develop swallowing dysfunction based on their neuroimaging. Clear models of swallowing control and integration of cortico-bulbar input have not been defined and the role of subcortical structures is unclear. The purpose of this study was to identify supratentorial regions of interest (ROIs) that might be related to clinically important dysphagia in acute stroke patients, focusing on subcortical structures. Methods— We studied 29 acute supratentorial ischemic stroke cases admitted to our institution between 2001 and 2005 diagnoses with first ischemic stroke and without history of swallowing dysfunction. Subjects had MRI within 24 hours. Cases were defined as those subjects who were diagnosed as dysphagic after clinical evaluation by a speech language pathologist (SLP) and whose dysphagia was considered clinically significant, ie, requiring treatment by diet modification. Controls were defined as those patients who: (1) passed the stroke unit’s dysphagia screening, (2) had a clinical evaluation by SLP that did not result in a diagnosis of dysphagia or diet modifications, or (3) had no documented evidence of dysphagia evaluation or treatment during hospitalization and were discharged on a regular diet. A trained technician, blinded to case–control status, examined 12 ROIs for dysfunctional tissue in diffusion and perfusion-weighted images. The odds ratio (OR) of dysphagia was calculated for each ROI. Logistic regression models were used to adjust for stroke severity (NIHSS) and volume. Results— Analysis of data on 14 cases and 15 controls demonstrated significant differences in the unadjusted odds of dysphagia for the following ROIs: (1) primary somatosensory, motor, and motor supplementary areas (PSSM; OR=10, P=0.009); (2) orbitofrontal cortex (OFC; OR=6.5, P=0.04); (3) putamen, caudate, basal ganglia (PCBG; OR=5.33, P=0.047); and (4) internal capsule (IC; OR=26; P=0.005). Nonsignificant differences were found in the insula and temporopolar cortex. Adjusted OR of dysphagia for subjects with strokes affecting the IC was 17.8 (P=0.03). Adjusted odds ratios for the PSSM, OFC, and PCBG were not statistically significant. Conclusion— Significantly increased odds of dysphagia were found in subjects with IC involvement. Other supratentorial areas that may be associated with dysphagia include the PSSM, OFC, and PCBG. Analysis of additional areas was limited by the number of subjects in our sample. Future studies with larger sample size are feasible and will contribute to the development of a full swallowing control model.Background—Dysphagia is a common problem after stroke associated with significant morbidity and mortality. Except for patients with brain stem strokes, particularly lateral medullary strokes, it is difficult to predict which cases are likely to develop swallowing dysfunction based on their neuroimaging. Clear models of swallowing control and integration of cortico-bulbar input have not been defined and the role of subcortical structures is unclear. Objective—To identify supratentorial regions of interest (ROIs) that might be related to clinically important dysphagia in acute stroke patients, focusing on subcortical structures. Methods—We studied 29 acute supratentorial ischemic stroke cases admitted to our institution between 2001 and 2005 diagnoses with first ischemic stroke and without history of swallowing dysfunction. Subjects had magnetic resonance imaging within 24 hours. Cases were defined as those subjects who were diagnosed as dysphagic after clinical evaluation by a speech language pathologist (SLP) and whose dysphagia was considered clinically significant i.e., requiring treatment by diet modification. Controls were defined as those patients who: (1) passed the stroke unit’s dysphagia screening, (2) had a clinical evaluation by SLP that did not result in a diagnosis of dysphagia or diet modifications, or (3) had no documented evidence of dysphagia evaluation or treatment during hospitalization and were discharged on a regular diet. A trained technician, blinded to case-control status, examined 12 ROIs for dysfunctional tissue in diffusion and perfusion-weighted images. The odds ratio (OR) of dysphagia was calculated for each ROI. Logistic regression models were used to adjust for stroke severity (NIHSS) and volume. Results—Analysis of data on 14 cases and 15 controls demonstrated significant differences in the unadjusted odds of dysphagia for the following ROIs: 1) primary somatosensory, motor and motor supplementary areas (PSSM) (OR=10, p=0.009); 2) orbitofrontal cortex (OFC)(OR=6.5, p=0.04); 3) putamen, caudate, basal ganglia (PCBG)(OR=5.33, p=0.047); and 4) internal capsule (IC)(OR=26; p=0.005). Non-significant differences were found in the insula and temporopolar cortex. Adjusted OR of dysphagia for subjects with strokes affecting the IC was 17.8 (p=0.03). Adjusted odds ratios for the PSSM, OFC, and PCBG were not statistically significant. Conclusion—Significantly increased odds of dysphagia were found in subjects with IC involvement. Other supratentorial areas that may be associated with dysphagia include the PSSM, OFC, and PCBG. Analysis of additional areas was limited by the number of subjects in our sample. Future studies with larger sample size are feasible and will contribute to the development of a full swallowing control model.

MRI Profile of the Perihematomal Region in Acute Intracerebral Hemorrhage

Background and Purpose— The pathophysiology of the presumed perihematomal edema immediately surrounding an acute intracerebral hemorrhage is poorly understood, and its composition may influence clinical outcome. Method— Twenty-three patients from the Diagnostic Accuracy of MRI in Spontaneous intracerebral Hemorrhage (DASH) study were prospectively enrolled and studied with MRI. Perfusion-weighted imaging, diffusion-weighted imaging, and fluid-attenuated inversion recovery sequences were coregistered. TMax (the time when the residue function reaches its maximum) and apparent diffusion coefficient values in the presumed perihematomal edema regions of interest were compared with contralateral mirror and remote ipsilateral hemispheric regions of interest. Results— Compared with mirror and ipsilateral hemispheric regions of interest, TMax (the time when the residue function reaches its maximum) and apparent diffusion coefficient were consistently increased in the presumed perihematomal edema. Two thirds of the patients also exhibited patchy regions of restricted diffusion in the presumed perihematomal edema. Conclusion— The MRI profile of the presumed perihematomal edema in acute intracerebral hemorrhage exhibits delayed perfusion and increased diffusivity mixed with areas of reduced diffusion.

Neural Correlates of Modality-specific Spatial Extinction

Sites of lesions responsible for visual, tactile, and/or motor extinction have not been clearly identified. We sought to determine the frequency of extinction in various modalities immediately after acute ischemic stroke, the rate of co-occurrence of extinction across modalities, and areas of infarct and/or hypoperfusion associated with each modality of extinction. A total of 148 patients with right supratentorial stroke were studied. In Study 1, 88 patients without hemiplegia, hemianesthesia, or visual field cuts were tested within 24 hours of onset for visual, tactile, and motor extinction, and underwent magnetic resonance diffusion and perfusion imaging. Associations between modality of extinction and areas of neural dysfunction (hypoperfusion/infarct) were identified. Of the 88 patients, 19 had only tactile extinction, 8 had only visual extinction, 12 had only motor extinction, 14 had extinction in two or more modalities, and 35 had no extinction. Tactile extinction was associated with neural dysfunction in the inferior parietal lobule; visual extinction was associated with dysfunction in the visual association cortex; and motor extinction was associated with neural dysfunction in the superior temporal gyrus. In Study 2, data from 60 patients who were excluded from Study 1 because of motor deficits were analyzed in the same way to determine whether frontal lesions contributed to visual or tactile extinction. Results again demonstrated that tactile extinction is associated with inferior parietal dysfunction, and visual extinction is associated with dysfunction of the visual association cortex. Potential accounts of the results, based on the hemisphere rivalry model of extinction and the limited attentional capacity model, are considered.