We addressed the general problem of finding an optimal scan schedule in positron emission tomography (PET) dynamic studies which minimises the errors in estimating the transfer constants between a set of compartments. As an example, the influence of scan intervals in PET on the accuracy of estimation of the rate constants and vascular component in the deoxyglucose method was examined using an empirical noise model. The simulated noisy curves used in the analysis were compared with patient data to validate the noise model. A series of scan schedules were compared for accuracy of fit by evaluating the determinant of the variance-covariance matrix of the fitted parameters as an index of parameter accuracy. For realistic noise levels there is a monotonic improvement in the index of parameter accuracy with increasing sampling frequency, particularly over the initial minutes after the tracer injection. However, since faster schedules are more susceptible to errors introduced by time mismatches between plasma and tissue curves and impose greater computational and memory overhead, an initial scan duration of 30 s provide a practical trade-off for dynamic PET 18F-fluoro-deoxyglucose studies.

Triple-tracer autoradiography was used to measure topographic changes in local cerebral blood flow, cerebral tissue pH, and local cerebral glucose utilization in hyperglycemic and normoglycemic rats, all of which had undergone occlusion of the middle cerebral artery. More severe and extensive reduction of all three variables was observed in the hyperglycemic than in the normoglycemic rats. In seven normoglycemic rats, significant reduction in local cerebral blood flow (p< 0.025) was observed in the ischemic but not in the contralateral nonischemic side at the lateral portion of the caudate nucleus and the neocortex. Tissue pH was significantly lower (p < 0.025) only at the lateral portion of the caudate nucleus in the ischemic side. No significant differences in local cerebral glucose utilization were observed when the two hemispheres were compared. In the ischemic hemisphere of five hyperglycemic rats, the caudate nucleus and the neocortex exhibited significant reduction (p< 0.025) in local cerebral blood flow, tissue pH, and local cerebral glucose utilization. Even in the nonischemic hemisphere of the hyperglycemic rats, local cerebral blood flow in the caudate nucleus and the neocortex was significantly reduced (p< 0.025) compared with the normoglycemic rats. No significant change in tissue pH or local cerebral glucose utilization was observed throughout the nonischemic hemisphere of the hyperglycemic compared with the normoglycemic rats. Tissue pH was systematically lower in the hyperglycemic than in the normoglycemic rats. The threshold level of local cerebral blood flow for tissue pH reduction was 49 ml/100 g/min with a 95% confidence interval of 46-54 ml/100 g/min in normoglycemic rats (37% of control) and 63 ml/100 g/min with a 95% confidence interval of 58-70 ml/100 g/min in hyperglycemic rats (47% of control). The threshold level of local cerebral blood flow for local cerebral glucose hyper metabolism was 20 ml/100 g/min with a 95% confidence interval, of 20-24 ml/100 g/min in normoglycemic rats (15% of control) and 30 ml/100 g/min with a 95% confidence interval of 30-49 ml/100 g/min in hypergfycemic rats (22% of control). (Stroke 1988;19:764-772)

The mechanism underlying the development of heart failure in this case is also discussed.

We studied the pharmacological mechanism of zonisamide (ZNS) using an electrophysiological and autoradiographical method in a limbic seizure model in rats. Limbic seizure status epilepticus was induced by a unilateral microinjection of kainic acid (KA) into the amygdala. Initially, observed seizures were limited to the side of the injected amygdala and then propagated to bilateral sensorimotor cortex. Eighty minutes after injection, secondarily generalized seizure status epilepticus was induced, with each seizure lasting approximately 30 s and recurring every 5 min. ZNS 100 mg/kg was administered intravenously (i.v.) during the generalized seizure. Forty minutes after ZNS administration, epileptic activity was observed only at the KA-injected amygdalar site and spikes were not observed in the bilateral sensorimotor cortex. We studied local cerebral glucose utilization (LCGU) after ZNS or saline administration using an autoradiographical method in the same limbic seizure preparation. In the ZNS group, LCGU decreased in the ipsilateral sensorimotor cortex and hippocampus, whereas in the controls LCGU increased in these structures. On the other hand, ZNS did not suppress the epileptic activity of the primary focus and no decrease in LCGU was observed in the KA-injected amygdala. ZNS inhibited seizure propagation from the epileptogenic focus but did not suppress the epileptic activity of the focus. Our results suggest that ZNS is effective for the treatment of secondarily generalized seizure.

Epilepsy surgery, as is employed for the management of intractable seizures, was performed in animals harboring a seizure focus induced by a local application of kainic acid (KA). Amygdalo-hippocampectomy failed to stop spontaneous seizures in the contralateral hippocampus. Callosotomy inhibited seizure propagation to the contralateral sensori-motor cortex. However, epileptic activity ipsilateral to the focus, including subcortical structures, persisted even after the callosotomy. Multiple subpial transection (MST) around the epileptic cortical focus suppressed the seizure activity of the cortex. However, seizure propagations in subcortical structures remained, even after MST. Niferacetam (a new nootropic agent) was tested in these models, and its promising effect on the intractable extratemporal epilepsy is reported.