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(Stroke. 1996;27:761-765.)
© 1996 American Heart Association, Inc.

Articles

Ischemic Stroke and Incomplete Infarction

Julio H. Garcia, MD; Niels A. Lassen, MD; Cornelius Weiller, MD; Bjørn Sperling, MD Jyoji Nakagawara, MD

From the Department of Pathology, Henry Ford Hospital, Detroit, Mich, and Case Western Reserve University School of Medicine, Cleveland, Ohio (J.H.G.); the Clinical Physiology and Nuclear Medicine Department, Bispebjerg Hospital, Copenhagen, Denmark (N.A.L., B.S.); Neurologische Klinik der Friedrich-Schiller-Universität Jena, Germany (C.W.); and the Department of Neurosurgery, Nakamura Memorial Hospital, Sapporo, Japan (J.N.).

Correspondence to Julio H. Garcia, MD, Neuropathology, Henry Ford Hospital, K-6 (A-610), 2799 W Grand Blvd, Detroit, MI 48202-2689.

	Abstract

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Background The concept of selective vulnerability or selective loss of individual neurons, with survival of glial and vascular elements as one of the consequences of a systemic ischemic-hypoxic insult (eg, transient cardiac arrest or severe hypotension), has been recognized for decades. In contrast, selective neuronal death as one of the lesions that may develop in the brain after occluding an intracranial artery is an idea not readily acknowledged in the current medical literature dealing with human stroke.

Summary of Review A review of pertinent publications reveals that selective neuronal injury after middle cerebral artery occlusion was observed in autopsy specimens over 40 years ago, although its pathogenesis remains unclear. Recent observations in both humans and animals suggest that selective neuronal necrosis (rather than infarct) is the consequence of either a short-term arterial occlusion or permanent occlusion accompanied by ischemia of moderate severity. During the acute and subacute stages of an ischemic stroke, the loss of a limited number of neurons (ie, incomplete infarction) does not result in structural changes discernible by either CT or conventional MRI. However, the loss of a selected number of neurons may be demonstrable in vivo by calculating the corresponding loss of benzodiazepine receptors. The use of specific radiotracers in combination with single-photon emission CT or positron emission tomography allows demonstration of a decrease in -aminobutyric acid–ergic receptor sites at places where many neurons have been lethally injured.

Conclusions We aim to alert physicians to the potential development of incomplete brain infarctions in patients with intracranial arterial occlusions. Recognizing incomplete infarcts is particularly important in the context of stroke therapy with thrombolytic and neuroprotective agents. This brain lesion is likely to be the consequence of an arterial occlusion with a resultant ischemia of moderate severity (eg, regional blood flows in the range of 15 to 20 mL·100 g^-1·min^-1).

Key Words: cerebral blood flow • cerebral cortex • cerebral ischemia • cerebral ischemia, transient • putamen

	Introduction

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The term "ischemic stroke" currently describes a focal neurological deficit attributable to the conditions created by the occlusion of an intracranial artery. A period of several hours or days elapses before the arterial occlusion produces an infarct,¹ a lesion defined as an area of coagulation necrosis of presumed ischemic origin that in most cases develops as a result of an arterial occlusion.² Areas of coagulation necrosis, in the brain but not in other organs, are typically replaced by a fluid-filled cavity several weeks or months after the original arterial occlusion. Under special circumstances—if the ischemia is of either short or moderate severity—arterial occlusions may induce brain lesions different from an infarct or area of pannecrosis. Because in such instances the necrosis affects only a limited number of cells and the long-term effect is not cavitation, the name "incomplete brain infarct" has been suggested for such lesions.³ The significance of incorporating this concept into the medical literature is underscored by these facts: the brain lesion, although not detectable by currently available neuroimaging methods such as CT and conventional MRI, may be demonstrable by functional neuroimaging with radioactive ligands that bind to specific neuroreceptors. Furthermore, patients in whom incomplete infarcts are likely to develop may experience significant improvement after belated reperfusion of the ischemic territory.

	Brief Historical Background

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Earlier in this century, several German authors described brain lesions of presumed ischemic (or hypoxic) origin in which tissue destruction was only partial.⁴ These histological changes, variously known as selective neuronal necrosis, selective neuronal loss, or selective neuronal injury, affect specific groups of neurons in the hippocampus, and the cerebellar cortex in particular, after transient episodes of global ischemia. According to Adams and Sidman,⁵ the injured neurons are identifiable by light microscopy as red neurons, provided that the ischemic event (such as severe hypotension) precedes death by a minimum of 6 hours, thus emphasizing the concept that the morphological expression of ischemic injury is delayed by several hours. We reviewed pertinent publications in search of answers to the question: Could comparable degrees of selective neuronal injury develop as a result of a single-artery occlusion?

According to Spatz,⁶ the autopsy features of human brains with MCA occlusion include unvollständigen Nekrosen or areas where the tissue changes are equivalent to incomplete infarcts. Presciently, Spatz suggested that tissue necrosis would affect only a portion of the cells within the ischemic area if the arterial occlusion were of short duration or if ischemia were of moderate severity.⁶ Testing the validity of such interpretations had to wait several decades until three different analyses could be applied to the same case: (1) angiographic demonstration of an arterial occlusion within 18 hours of the stroke; (2) demonstration of two or more areas supplied by the occluded artery, where the magnitude of local CBF decreases were significantly different from one another; and finally (3) histopathologic corroboration of two different tissue responses: pannecrosis with cavitation in some areas and selective neuronal necrosis in adjacent sites.

Scholz⁷ defined elektive Parenchymnekrose as a type of ischemic brain injury in which, in the chronic stages, the tissue responses would lead to local tissue atrophy without cavitation; at these sites, because astroglia and some neurons survive and thus the skeleton of the brain tissue is preserved, neither softening (or emollition) nor cavitation would develop. In addition to selective neuronal necrosis, which classically is associated with injury secondary to global ischemia and carbon monoxide intoxication, Scholz observed that elektive Parenchymnekrose may also occur in certain unspecified instances of ischemic stroke.⁷

Contemporary textbooks of neuropathology do not mention selective neuronal necrosis or elective neuronal injury as one of the possible outcomes of an arterial occlusion in humans,^{8 9 10 11 12 13 14} but one study exists of two patients with ischemic stroke in whom large brain areas of incomplete infarcts were demonstrated.¹⁵ The two patients were selected from a group of 105 consecutively studied patients with ischemic strokes in whom CBF had been calculated with intracarotid injection of ¹³³Xe. Angiography performed within a few hours of the stroke demonstrated MCA occlusion in both cases; in each patient, an area of CT hypodensity involving the basal ganglia was surrounded by a larger area, where CBF values were in the range of 20 to 25 mL·100 g^-1·min^-1 (ie, "moderate" ischemia). Both patients had atrial fibrillation and both died with a second ischemic injury to the opposite cerebral hemisphere, 3 or 34 months after the initial stroke. At autopsy, the originally affected hemisphere showed a cavitary infarct in the basal ganglia and a much larger peripheral area within the territory of the MCA, where >50% loss of neurons and gliosis was histologically demonstrated. On CT examination, these areas were isodense with respect to the normal brain.¹⁵

	Experimental Observations

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Selective neuronal necrosis with sparing of glia and microvessels has been experimentally induced in macaques by transient occlusion of the MCA,¹⁶ but the potential application of those observations to the human condition of ischemic stroke remains incompletely appreciated.

In experiments based on permanent occlusion of the MCA stem, necrosis nearly always involves both the subcortical structures and the adjacent cortex^{1 17} ; however, pannecrosis is not demonstrable in the vulnerable areas before 72 hours. Moreover, compared with the caudoputamen, neuronal necrosis is delayed in the cortex by more than a few hours.¹⁸ Several weeks after experimental arterial occlusions, the brain lesions become sharply demarcated, although outside the edges of the infarct selective neuronal loss has been observed in rats,¹⁷ cats,¹⁹ and baboons.²⁰

All experimental studies of transient MCA occlusion that include measurements of rCBF and histological evaluation of the brain (>24 hours after the arterial occlusion) report selective neuronal loss in the originally ischemic areas, with the extent of the neuronal loss being dependent on either duration or severity of the ischemia.^{21 22 23 24 25 26} In those studies, incomplete necrosis of the ischemic brain was seen after either a few hours of mild ischemia (rCBF, 15 to 18 mL·100 g^-1·min^-1) or short periods of severe ischemia (rCBF, 8 mL·100 g^-1 · min^-1). In contrast, all areas where the rCBF fell below 10 to 12 mL·100 g^-1·min^-1 for periods of 1 hour or longer eventually developed pannecrosis followed by cavitation; longer ischemic periods were tolerated almost indefinitely in areas where the rCBF remained above 18 to 20 mL·100 g^-1·min^-1.²¹ The Figure is a composite summary showing the results of those experiments and illustrating the time-severity relationship that exists between ischemia and neuronal viability.

View larger version (26K): [in this window] [in a new window]   Figure 1. Graph shows the time-intensity relationship of ischemia and incomplete infarction. The area above the curves represents the combination of duration and intensity of ischemia that is tolerated without development of infarction, whereas points below the curves will result in infarction. The curves are modified from the work of Jones et al23 (straight line) on monkeys and Heiss and Rosner21 (dashed line) on single neurons. Each + represents a single point of duration and intensity of ischemia resulting in incomplete infarction in animal models of transient focal ischemia.21 22 23 24 25 26 48 Thus the shaded area is suggested as the combination of duration and intensity of ischemia that will lead to incomplete infarction,45 illustrating the continuum from normal condition to incomplete infarction and infarction.

In a recent study comparing the effects of transient versus permanent MCA occlusion (7-day duration) in rats, pannecrosis was typical of cases in which the artery remained occluded, whereas selective neuronal injury (without cavitation) characterized the brain lesion in experiments with transient occlusion followed by a week of survival.²⁷ More importantly, a close correlation (r=.951) existed between the mean number of necrotic neurons and the severity of the neurological deficit expressed as a mean of the neurological scores for each experimental subgroup. Lastly, the study demonstrated that with prolonged survival, areas of incomplete infarction do not evolve into a complete infarct.²⁷ Transient MCA occlusion causes selective neuronal necrosis (cytoplasmic eosinophilia)²⁷ as well as DNA fragmentation; some authors interpret the latter as a sign of apoptosis.²⁸ Activation of endonucleases with nuclear fragmentation and ingestion of the injured cell by a macrophage is the mechanism of cell death originally described under the name apoptosis; this mechanism is believed to explain the disappearance of excessive cells during organogenesis.^{29 30} In addition to anoxia and ischemia/reperfusion (in the kidney), apoptosis may also be inducible by the effects of excitotoxic neurotransmitters such as glutamate.^{30 31} Both apoptosis and the effects of glutamate on the N-methyl-D-aspartate receptors can be counteracted in ways that could become the basis of future therapeutic trials of ischemic stroke.^{31 32}

	Clinical Significance of Incomplete Infarction

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MCA Occlusion Accompanied by Subcortical Infarcts Alone
In a study of 57 patients with MCA occlusion, Weiller et al³³ observed large areas of CT hypodensity in the striatum/internal capsule without involvement of the adjacent cortex. Clinical inference, corroborated in most instances by angiography, suggested that each of the 57 patients had suffered a recent embolic occlusion of the MCA stem, a type of occlusion that is prone to undergo spontaneous lysis with subsequent reperfusion of the ischemic territory.³⁴ Cortical dysfunction (ie, aphasia with or without hemineglect) of the opercular or temporal area was demonstrable in about one half of these patients. Angiography and ^99mTc–hexamethylpropyleneamine oxime tomography in this subgroup of patients showed evidence of inadequate collateral blood flow to the cortex. The authors concluded that in this subgroup of patients the cortex may have been affected by ischemia of moderate severity and thence by incomplete infarction; 1 year later they uncovered supportive evidence in most cases in the form of focal cortical atrophy involving the insular and temporal cortices. Of interest, the clinical symptoms attributed to cortical dysfunction had largely but not entirely disappeared despite the cortical atrophy demonstrable on MRI.²⁹

Early Reperfusion in Embolic Stroke
Whether occurring spontaneously or following thrombolysis, reperfusion after a short ischemic period should induce incomplete infarction rather than pannecrosis. The duration of a "short" ischemic period may range from 1 to 12 hours, depending on the level of residual collateral blood flow, as suggested in the Figure. Successful reopening of the artery should lead to partial salvage of an ischemic area; infarction and pannecrosis may not develop. Instead, selective neuronal necrosis of variable degrees will reflect the severity of the insult. Neuroprotective drugs given 30 minutes before MCA occlusion seemingly protect incomplete infarcts while failing to reduce the volume of the core of the lesion.³⁵ This suggests that the combined use of both measures, reopening the artery and administering neuroprotective agents, may be beneficial in the treatment of appropriately selected types of ischemic stroke.³⁶

Circulating neuroprotective agents probably cannot effectively reach areas where CBF is extremely low, and this may explain their lack of universal effectiveness. In contrast, hypothermia (the prototypical neuroprotective agent) in principle can be effective in the ischemic core as well as in the margins.³⁷ Systemic hypothermia induced 30 minutes before the arterial occlusion in rats with transient MCA occlusion significantly altered the histological responses.³⁸ Yet mild hypothermia as a basic therapy for human ischemic stroke has not been implemented, probably because the development of methods to institute brain hypothermia and evaluate its cost-benefit ratio still await exploration. Inducing moderate hypoglycemia as a therapy for human ischemic stroke has also been suggested by observations made in experimental models.

The ability to protect brain areas injured by incomplete infarction will depend on elucidating the mechanism(s) responsible for cell death. Selecting the appropriate therapeutic agent will be guided by the development of methods that can identify in vivo the most likely operative mechanism(s).

Imaging Incomplete Brain Infarcts
Whereas most (about 70%) ischemic strokes are associated with either CT or MRI changes that become visible some hours after the stroke,³⁹ as well as throughout the subacute and chronic phases, incomplete infarcts are not visible as hypodense areas on CT; this is because the gross structure of the brain tissue is preserved¹⁵ in incomplete infarcts.

Selective neuronal necrosis with preservation of some neurons, glia, and microvessels defines an incomplete infarct; therefore, its diagnosis would require histopathologic verification. A new technique of brain imaging has emerged, however, that holds promise as a tool for the in vivo diagnosis of incomplete infarct. The method is based on the use of a radioactive tracer of the central benzodiazepine receptor.⁴⁰ This receptor, part of the GABAergic complex, is widely distributed in the cerebral cortex, where it is highly concentrated as a reflection of the abundant GABAergic inhibitory synapses that normally exist there. The cortical synapse-rich neuropil probably contains more GABAergic synapses than the sum of all excitatory synapses taken together. Therefore, measuring the concentration of the benzodiazepine receptor (its V_max) can be taken as an approximate measure of the number of synapses and hence as an indicator of the intactness of the cortical neurons.^{40 41 42}

¹¹C-Labeled flumazenil (RO 15 1788) and ¹³³I-labeled iomazenil (RO 16 0154) bind specifically to the benzodiazepine receptors. This allows accurate quantification of the tracer using either positron emission tomography or single-photon emission CT. These ligands do not bind infarcted or pannecrotic brain areas as reported by Sette et al,⁴³ who analyzed the effects of permanent versus transient (3 to 6 hours) MCA occlusion in baboons and identified in vivo subcortical "infarcts" by the typical CT-hypodense lesion. However, they also detected an approximate 20% decrease of benzodiazepine receptor binding in the CT-intact opercular cortex adjacent to the hypodense area. The authors suggested that this borderline-ischemic cortex where blood was supplied by pial collateral vessels had suffered partial or selective neuronal necrosis without loss of glial cells, and as a consequence the gross tissue structure had remained "intact" on CT⁴³ ; we suggest that these are areas of incomplete infarct.

The experiments of Sette et al⁴³ were terminated 3 months after the MCA occlusion, and histological evaluation has uncovered evidence of selective neuronal loss and gliosis in the insular cortex of some of the brains subjected to transient MCA occlusion.⁴⁴ These data are currently being correlated with the in vivo data on CBF and the data on benzodiazepine receptor binding derived from the same animals. Such analysis will afford a critical and decisive test of the feasibility of diagnosing incomplete infarcts in humans. Comparable observations (ie, loss of benzodiazepine receptor binding in regions peripheral to the CT-hypodense areas) have been made in a selected number of patients with proven intracranial arterial occlusions in whom there was evidence of robust, efficient collateral blood flow and early reperfusion.⁴⁵

	Concluding Remarks

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Early reperfusion of ischemic brain areas in patients with ischemic stroke is currently being explored as a therapeutic modality.³⁴ This is in accord with the therapeutic principles currently applied to acute coronary occlusion, in which early reperfusion leads to selective parenchymal (myocyte) necrosis in areas that otherwise would have undergone infarction.^{46 47}

The marked vulnerability of brain tissue to ischemia suggests that the therapy of ischemic stroke with thrombolytic and neuroprotective agents can only result in partial salvage of tissue in most cases. Selecting patients who have adequate collateral (or residual) blood flow seems to be the most promising approach that may lead to substantial benefits without exposing the patient to undue risks. Areas where the CBF ranges between 15 and 20 mL·100 g^-1·min^-1 may enjoy a wider "therapeutic window" and may benefit from reperfusion when compared with areas where CBF values are 10 mL·100 g^-1·min^-1. Also, circulating neuroprotective agents may reach the former areas more readily and thus may further widen the window. The realistic goal of therapy for ischemic stroke is to salvage marginally perfused areas and keep the infarct to the smallest size possible. We surmise that to document such partial salvage it is necessary to identify by either positron emission tomography or single-photon emission CT the fairly discrete ischemic brain areas we call incomplete infarctions.

Currently available neuroimaging methods do not identify the operative mechanism(s) of lethal injury. Consequently, evaluating the success of future therapeutic interventions will necessitate the development of tools that can distinguish between lethal and sublethal types of injury.

	Selected Abbreviations and Acronyms

 

CBF = cerebral blood flow GABA = -aminobutyric acid MCA = middle cerebral artery rCBF = regional cerebral blood flow

	Acknowledgments

 
Financial support was partly derived from US Public Health Service grant NS-31631 (Dr Garcia) and the Alfred Benzon Foundation of Copenhagen, Denmark. The authors gratefully acknowledge the secretarial support of Marjorie Weiß (Essen, Germany), Paula McGee, Kathy Zajas, and Kathleen Hessell (Detroit).

Received September 5, 1995; revision received January 3, 1996; accepted January 3, 1996.

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				K. M. Sicard, N. Henninger, M. Fisher, T. Q. Duong, and C. F. Ferris Long-Term Changes of Functional MRI-Based Brain Function, Behavioral Status, and Histopathology After Transient Focal Cerebral Ischemia in Rats Stroke, October 1, 2006; 37(10): 2593 - 2600. [Abstract] [Full Text] [PDF]

				D. Saur, R. Lange, A. Baumgaertner, V. Schraknepper, K. Willmes, M. Rijntjes, and C. Weiller Dynamics of language reorganization after stroke Brain, June 1, 2006; 129(6): 1371 - 1384. [Abstract] [Full Text] [PDF]

				S. Kuroda, T. Shiga, K. Houkin, T. Ishikawa, C. Katoh, N. Tamaki, and Y. Iwasaki Cerebral Oxygen Metabolism and Neuronal Integrity in Patients With Impaired Vasoreactivity Attributable to Occlusive Carotid Artery Disease Stroke, February 1, 2006; 37(2): 393 - 398. [Abstract] [Full Text] [PDF]

				H. Yamauchi, T. Kudoh, Y. Kishibe, J. Iwasaki, and S. Kagawa Selective Neuronal Damage and Borderzone Infarction in Carotid Artery Occlusive Disease: A 11C-Flumazenil PET Study J. Nucl. Med., December 1, 2005; 46(12): 1973 - 1979. [Abstract] [Full Text] [PDF]

				O Y Bang, P H Lee, K G Heo, U S Joo, S R Yoon, and S Y Kim Specific DWI lesion patterns predict prognosis after acute ischaemic stroke within the MCA territory J. Neurol. Neurosurg. Psychiatry, September 1, 2005; 76(9): 1222 - 1228. [Abstract] [Full Text] [PDF]

				A. Shiraishi, Y. Hasegawa, S. Okada, K. Kimura, T. Sawada, H. Mizusawa, and K. Minematsu Highly Diffusion-Sensitized Tensor Imaging of Unilateral Cerebral Arterial Occlusive Disease AJNR Am. J. Neuroradiol., June 1, 2005; 26(6): 1498 - 1504. [Abstract] [Full Text] [PDF]

				H Yamauchi, T Kudoh, K Sugimoto, M Takahashi, Y Kishibe, and H Okazawa Pattern of collaterals, type of infarcts, and haemodynamic impairment in carotid artery occlusion J. Neurol. Neurosurg. Psychiatry, December 1, 2004; 75(12): 1697 - 1701. [Abstract] [Full Text] [PDF]

				S. Kuroda, T. Shiga, T. Ishikawa, K. Houkin, T. Narita, C. Katoh, N. Tamaki, and Y. Iwasaki Reduced Blood Flow and Preserved Vasoreactivity Characterize Oxygen Hypometabolism Due to Incomplete Infarction in Occlusive Carotid Artery Diseases J. Nucl. Med., June 1, 2004; 45(6): 943 - 949. [Abstract] [Full Text] [PDF]

				G. J. del Zoppo TIAs and the pathology of cerebral ischemia Neurology, April 27, 2004; 62(8_suppl_6): S15 - S19. [Full Text]

				J. Hijjawi, J. E. Mogford, L. A. Chandler, K. J. Cross, H. Said, B. A. Sosnowski, and T. A. Mustoe Platelet-Derived Growth Factor B, but Not Fibroblast Growth Factor 2, Plasmid DNA Improves Survival of Ischemic Myocutaneous Flaps Arch Surg, February 1, 2004; 139(2): 142 - 147. [Abstract] [Full Text] [PDF]

				H. Yamauchi, H. Okazawa, K. Sugimoto, Y. Kishibe, and M. Takahashi The Effect of Deafferentation on Cerebral Blood Flow Response to Acetazolamide AJNR Am. J. Neuroradiol., January 1, 2004; 25(1): 92 - 96. [Abstract] [Full Text] [PDF]

				A. Sarrafzadeh, D. Haux, O. Sakowitz, G. Benndorf, H. Herzog, I. Kuechler, and A. Unterberg Acute Focal Neurological Deficits in Aneurysmal Subarachnoid Hemorrhage: Relation of Clinical Course, CT Findings, and Metabolite Abnormalities Monitored With Bedside Microdialysis Stroke, June 1, 2003; 34(6): 1382 - 1388. [Abstract] [Full Text] [PDF]

				S. T. Carmichael Plasticity of Cortical Projections after Stroke Neuroscientist, February 1, 2003; 9(1): 64 - 75. [Abstract] [PDF]

				G. W. Albers, L. R. Caplan, J. D. Easton, P. B. Fayad, J.P. Mohr, J. L. Saver, D. G. Sherman, and the TIA Working Group Transient Ischemic Attack -- Proposal for a New Definition N. Engl. J. Med., November 21, 2002; 347(21): 1713 - 1716. [Full Text] [PDF]

				W. Droge Free Radicals in the Physiological Control of Cell Function Physiol Rev, January 1, 2002; 82(1): 47 - 95. [Abstract] [Full Text] [PDF]

				D. Mungas, W. J. Jagust, B. R. Reed, J. H. Kramer, M. W. Weiner, N. Schuff, D. Norman, W. J. Mack, L. Willis, and H. C. Chui MRI predictors of cognition in subcortical ischemic vascular disease and Alzheimer's disease Neurology, December 26, 2001; 57(12): 2229 - 2235. [Abstract] [Full Text] [PDF]

				J. Hendrikse, M. J. Hartkamp, B. Hillen, W. P.T.M. Mali, and J. v. d. Grond Collateral Ability of the Circle of Willis in Patients With Unilateral Internal Carotid Artery Occlusion: Border Zone Infarcts and Clinical Symptoms Stroke, December 1, 2001; 32(12): 2768 - 2773. [Abstract] [Full Text] [PDF]

				S. Kuroda, K. Houkin, H. Kamiyama, K. Mitsumori, Y. Iwasaki, H. Abe, H. Yonas, L. R. Wechsler, E. Nemoto, and R. Pindzola Long-Term Prognosis of Medically Treated Patients With Internal Carotid or Middle Cerebral Artery Occlusion: Can Acetazolamide Test Predict It? Editorial Comment: Can Acetazolamide Test Predict It? Stroke, September 1, 2001; 32(9): 2110 - 2116. [Abstract] [Full Text] [PDF]

				O. A. Selnes, R. M. Royall, M. A. Grega, L. M. Borowicz Jr, S. Quaskey, and G. M. McKhann Cognitive Changes 5 Years After Coronary Artery Bypass Grafting: Is There Evidence of Late Decline? Arch Neurol, April 1, 2001; 58(4): 598 - 604. [Abstract] [Full Text] [PDF]

				G. Fein, V. Di Sclafani, J. Tanabe, V. Cardenas, M. W. Weiner, W. J. Jagust, B. R. Reed, D. Norman, N. Schuff, L. Kusdra, et al. Hippocampal and cortical atrophy predict dementia in subcortical ischemic vascular disease Neurology, December 12, 2000; 55(11): 1626 - 1635. [Abstract] [Full Text] [PDF]

				D.-W. Kang, J.-K. Roh, Y.-S. Lee, I. C. Song, B.-W. Yoon, and K.-H. Chang Neuronal metabolic changes in the cortical region after subcortical infarction: a proton MR spectroscopy study J. Neurol. Neurosurg. Psychiatry, August 1, 2000; 69(2): 222 - 227. [Abstract] [Full Text] [PDF]

				H. Yamauchi, H. Fukuyama, Y. Nagahama, C. Oyanagi, H. Okazawa, M. Ueno, J. Konishi, and H. Shio Long-term changes of hemodynamics and metabolism after carotid artery occlusion Neurology, June 13, 2000; 54(11): 2095 - 2102. [Abstract] [Full Text] [PDF]

				C. Wong Paraplegia after coronary artery bypass operations: Relationship to severe hypertension and vascular disease J. Thorac. Cardiovasc. Surg., June 1, 2000; 119(6): 1295 - 1296. [Full Text]

				T. ERKINJUNTTI, D. INZITARI, L. PANTONI, A. WALLIN, P. SCHELTENS, K. ROCKWOOD, and D. W. DESMOND Limitations of Clincal Criteria for the Diagnosis of Vascular Dementia in Clinical Trials: Is a Focus on Subcortical Vascular Dementia a Solution? Ann. N.Y. Acad. Sci., April 1, 2000; 903(1): 262 - 272. [Abstract] [Full Text] [PDF]

D. INZITARI, T. ERKINJUNTTI, A. WALLIN, T. DEL SER, M. ROMANELLI, and L. PANTONI Subcortical Vascular Dementia as a Specific Target for Clinical Trials Ann. N.Y. Acad. Sci.,