Behavioral neurology in the emergency room Language testing brain imaging and acute stroke therapy.код для вставкиСкачать
EDITORIAL Behavioral Neurology in the Emergency Room: Language Testing, Brain Imaging, and Acute Stroke Therapy Behavioral neurology has often been considered the most theoretical and least practical area of neurology, the province of armchair philosophers and students of the mind–brain relationship. Detailed structure–function analyses, such as the anatomical basis of language comprehension or of lexical–semantic relationships (words and their meanings), have held limited interest for practicing neurologists. Aphasiology has been controversial, with some experts finding little consistent relationship between specific sites of brain injury and aphasic phenomena.1 Functional brain imaging of cortical networks promises to clarify these inconsistencies in brain–language correlation.2 Imaging of acute stroke, before recovery and compensation for damaged areas, may provide another window into the relationships of language function and brain structure. The advent of acute stroke interventions has brought behavioral neurology into the acute treatment arena, just as it has forced practicing neurologists out of the office and into the emergency room. Revascularization therapies, such as intravenous3 and intraarterial4 thrombolytic therapy, have highlighted the need to identify brain areas at risk of irreversible damage, but that are still salvageable if flow can be restored. Speech, language, and cognition are among the most critical functions to preserve in a stroke patient. New parameters of magnetic resonance imaging (MRI) have aided the diagnosis of acute stroke. Perfusion-weighted imaging (PWI) identifies ischemic tissue at risk of infarction, whereas diffusion-weighted imaging (DWI) indicates tissue with cytotoxic edema, already infarcted or on the verge of infarction. The difference between the diffusion and perfusion defects, the “diffusion–perfusion mismatch,” is thought to represent the “ischemic penumbra.”5,6 This oft-quoted theory of the diffusion–perfusion mismatch, however, requires correlation with clinical outcome measures. In previous research, Hillis and colleagues7 demonstrated that behavioral detection of aphasic deficits or neglect in acute stroke patients correlated with hypoperfusion on PWI and that improved perfusion by blood pressure elevation or carotid endarterectomy resulted in both recovery of the clinical deficit and reduction of the PWI defect. Thus, the authors demonstrated that testing of cognitive functions and the finding of a diffusion–perfusion mismatch have practi- cal value in the treatment of acute stroke patients. Hillis and colleagues8 presented a patient with a left frontotemporal stroke in whom hypotension appeared to worsen both the perfusion of Wernicke’s area and language deficits; blood pressure elevation improved both perfusion and language function. In this issue of the Annals of Neurology, Hillis and colleagues9 provide quantitative evidence that the perfusion defects noted on MRI correlate with the clinical deficits in a specific language function. The authors correlated delayed perfusion (time to peak on PWI) of Brodmann’s area 22, the traditional Wernicke’s area, relative to the analogous right hemisphere area, with deficits in spoken word–picture (lexical–semantic) matching in 50 patients with acute left middle cerebral artery territory ischemia; 29 additional patients were excluded because of a diffusion defect indicating an infarct, in which the degree of perfusion would not be expected to correlate with language function. The delay in perfusion of area 22 correlated quantitatively with the degree of lexical– semantic deficit; a delay of longer than 2.5 seconds to peak perfusion was predictive of loss of lexical–semantic ability. The implications of this research are important both for the understanding of language function and for the scientific basis of acute stroke therapy. First, these results clearly establish the critical importance of the cortical Wernicke’s area for single word comprehension, a finding also supported by poststroke CT research.10,11 Second, they show that a perfusion defect on MRI indicates a loss of function of the affected cortex. PWI, along with clinical examination, should guide the use of thrombolytic agents. For the future, further research is needed to prove that revascularization of a hypoperfused area on PWI will restore function and improve clinical outcome. Kidwell and colleagues (University of California at Los Angeles)12 have shown that diffusion MRI does not always indicate irreversibly infarcted brain and that thrombolytic therapy can reduce the diffusion defect. Use of thrombolytic therapy has not been proved effective beyond the 6-hour window of the PROACT II study,4 although a potential may exist in patients who continue to show a diffusion–perfusion mismatch beyond this time. As Hillis and associates7,8 have shown, simpler measures, such as induced hypertension, improve perfusion in such cases. © 2001 Wiley-Liss, Inc. 559 Hypotension in the setting of hypoxia or stroke worsens brain injury in animal models13 and in patients,14 but the use of pressor agents to raise blood pressure will require specific clinical trial evidence to become a routine recommendation. Rordorf and colleagues15 have reported encouraging results in 7 of 13 patients treated with phenylephrine. Methods such as those of Hillis and coworkers7–9 should be at the forefront of research into this treatment strategy, and neurologists interested in cognitive function should emulate their practical application of these techniques in the emergency room. Howard S. Kirshner, MD Department of Neurology Vanderbilt University School of Medicine Nashville, TN References 1. Willmes K, Poeck K. To what extent can aphasic syndromes be localized? Brain 1993;116:1527–1540. 2. Kirshner HS. Language studies in the third millennium. Brain Lang 2000;71:124 –128. 3. NINDS rt-PA Stroke Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581–1587. 4. Furlan AJ, Higashida R, Wechsler L, et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. JAMA 1999;282:2003–2011. 560 Annals of Neurology Vol 50 No 5 November 2001 5. Fisher M, Garcia JH. Evolving stroke and the ischemic penumbra. Neurology 1996;47:884 – 888. 6. Schlaug G, Benfield BS, Baird AE, et al. The ischemic penumbra: operationally defined by diffusion and perfusion MRI. Neurology 1999;53:1528 –1537. 7. Hillis AE, Barker P, Beauchamp N, et al. MR perfusion imaging reveals regions of hypoperfusion associated with aphasia and neglect. Neurology 2000;55:782–788. 8. Hillis AE, Kane A, Barker P, et al. Restoring blood pressure reperfused Wernicke’s area and improved language. Neurology 2001;56:670 – 672. 9. Hillis AE, Wityk RJ, Tuffiash E, et al. Hypoperfusion of Wernicke’s area predicts severity of semantic deficit in acute stroke. Ann Neurol 2001;50:561–566. 10. Selnes OA, Niccum N, Knopman DS, Rubens AB. Recovery of single word comprehension: CT-scan correlates. Brain Lang 1984;21:72– 84. 11. Naeser MA, Helm-Estabrooks N, Haas G, et al. Relationship between lesion extent in “Wernicke’s area” on computed tomographic scan and predicting recovery of comprehension in Wernicke’s aphasia. Arch Neurol 1987;44:73– 82. 12. Kidwell CS, Saver JL, Mattiello J, et al. Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/ perfusion magnetic resonance imaging. Ann Neurol 2000;47: 462– 469. 13. Kirschner HS, Blank WF Jr, Myers RE. Changes in cortical subarachnoid fluid potassium concentrations during hypoxia. Arch Neurol 1976;33:83–90. 14. Lavin P. Management of hypertension in patients with acute stroke. Arch Intern Med 1986;146:66 – 68. 15. Rordorf G, Koroshetz WJ, Ezzeddine MA, et al. A pilot study of drug-induced hypertension for treatment of acute stroke. Neurology 2001;56:1210 –1213.