Spontaneous neurological recovery after stroke and the fate of the ischemic penumbra

Abstract

We prospectively tested the hypothesis that early recovery after ischemic stroke depends on the ultimate survival of functionally impaired, critically ischemic (i.e., "penumbral") tissue. From a series of 26 consecutive patients studied with positron emission tomography within 18 hours of first-ever stroke in the middle cerebral artery territory, all 11 survivors to the 2-month end point who exhibited increased oxygen extraction fraction were declared eligible. The positron emission tomographic images were compared to ultimate infarction defined by computed tomography performed during the chronic stage. The penumbra (operationally defined by increased oxygen extraction fraction and divided outcome despite uniformly reduced cerebral blood flow) was individually detected in 10 of the 11 patients; cerebral blood flow ranged from 7 to 17 ml/100 gm x min, consistent with that found in monkey studies. The volume of the penumbra that escaped infarction was highly correlated with neurological recovery (p < 0.04 to p < 0.0001, depending on the scale used). This longitudinal study is the first to characterize the penumbra in humans and to document one mechanism strongly influencing recovery; the surviving penumbra may offer opportunities for secondary perifocal neuronal reorganization. Therapeutic measures to prevent infarction of the penumbra (up to 16 hours in this series) may have reduced residual neurological impairment. Mapping the extent of the penumbra, according to prospective criteria, may allow one to predict each patient's potential for recovery, and to select the most appropriate candidates for therapeutic trials.

Selective Neuronal Loss in Ischemic Stroke and Cerebrovascular Disease

“…These apparent discrepancies might reflect species differences but also the small degree of neuronal death in S1, the lack of co-registration between fMRI and histopathology, and the fact that fMRI was performed under general anesthesia, in the Sicard study. 42 Behavioral Correlates Although avoiding infarction of the penumbra markedly benefits behavioral outcome, 86,87 whether SNL may limit or delay functional recovery and plastic processes in the immediate periinfarct tissue, known to partly underlie recovery after cortical stroke, 86,88,89 is an important issue. In rats subjected to 20-minute proximal tMCAo inducing striatal SNL together with mild and inconsistent cortical SNL, Sicard et al 42 reported initial impairment but eventual full recovery in 3 weeks of subtle motor functions assessed by the adhesive test, which has been suggested to be specific to cortical lesions.…”

Cerebral Metabolic Response to Low Blood Flow: Possible Role of Cytochrome Oxidase Inhibition

“…An extreme range of reductions were observed in the left thalamus, ranging from 4% to 54%. In no region did the CBF approach the conventionally accepted ischemic threshold of 20 mL/hg min (Purves, 1972;Furlan et al, 1996;Marchal et al, 1996).…”

Effects of glucose concentration on redox status in rat primary cortical neurons under hypoxia

“…Cerebral ischemia causes dynamic and heterogeneous alterations of oxygen and glucose supplies and cellular metabolism [6,25]. Decreased level of glucose in ischemia is believed to play an important role in ischemic injury.…”