Fumiaki Oka

The influence of focal brain cooling on neurophysiopathology: validation for clinical application

OBJECT Focal brain cooling has been recognized to have a suppressive effect on epileptiform discharges or a protective effect on brain tissue. However, the precise influence of brain cooling on normal brain function and histology has not yet been thoroughly investigated. The aim of this study was to investigate the neurophysiopathological consequences of focal cooling and to detect the threshold temperature that causes irreversible histological change and motor dysfunction. METHODS The experiments were performed in adult male Sprague-Dawley rats (weighing 250-350 g) after induction of halothane anesthesia. A thermoelectric chip (6 x 6 x 2 mm) was used as a cooling device and was placed on the surface of the sensorimotor cortex after a 10 x 8-mm craniotomy. A thermocouple was placed between the chip and the brain surface. Focal cooling of the cortex was performed at the temperatures of 20, 15, 10, 5, 0, and -5 degrees C for 1 hour (5 rats in each group). Thereafter, the cranial window was repaired. Motor function was evaluated using the beam-walking scale (BWS) every day for 7 days. The rats were killed 7 days after the operation for histological examination with H & E, Klüver-Barrera, glial fibrillary acidic protein, and terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate nick-end labeling stainings. The authors also euthanized some rats 24 hours after cooling and obtained brain sections by the same methods. RESULTS The BWS score was decreased on the day after cooling only in the -5 degrees C group (p < 0.05), whereas the score did not change in the other temperature groups. Histologically, the appearance of cryoinjury such as necrosis, apoptosis, loss of neurons, and marked proliferation of astrocytes at the periphery of the lesion was observed only in the -5 degrees C group, while no apparent changes were observed in the other temperature groups. CONCLUSIONS The present study confirmed that the focal cooling of the cortex for 1 hour above the temperature of 0 degrees C did not induce any irreversible histological change or motor dysfunction. These results suggest that focal brain cooling above 0 degrees C has the potential to be a minimally invasive and valuable modality for the treatment of severe brain injury or to assist in the examination of brain function.

Ischemic stroke due to dissection of intracranial internal carotid artery: implications for early surgical treatment

BACKGROUND Intracranial ICA dissection is a rare pathology that frequently results in severe morbidity or mortality in young patients. This study examined the suitability of early surgical treatment. METHODS We present and analyze 6 of our own cases and 39 other cases reported after 1980. The clinical courses were classified into 3 types: A, single attack and severe outcome; B, single attack and mild to moderate outcome; and C, recurrent attacks and various outcomes. RESULTS Type A patients (n = 11) usually deteriorated quickly and severely so that early surgical treatment was not possible. Most type B patients (n = 12) did not require surgical intervention because of relatively stable courses. Only some type C patients (n = 10) are candidates for early surgery to prevent progressive deterioration. Twelve cases were unclassified because of insufficient information. We encountered 3 cases of type C, and emergency bypass surgery with parent ICA occlusion was planned in 2 patients. The surgery was successful with good prognosis in 1 patient; but the ICA and its branches were already occluded in the other patient, which precluded completion of bypass surgery and resulted in severe hemiparesis. Intraoperative findings and histologic examination of the MCA confirmed arterial dissection. CONCLUSION Young patients with intracranial ICA dissection manifesting as mild ischemic stroke should be considered for early bypass surgery with occlusion of the dissected ICA if any sign of progression or recurrence occurs after the onset.

Cognitive outcome differences on the side of carotid artery stenting

OBJECTIVE The right and left sides of the brain play different roles in cognition. Therefore, the side of treatment should be taken into consideration when evaluating cognitive outcome following revascularization. Thus, we designed a study to evaluate changes in right hemisphere cognitive function in patients undergoing right carotid artery stentings (CAS) and left hemispheric cognitive function in patients undergoing left CAS. In addition, we studied CAS-related changes in regional cerebral blood flow to determine potential correlations with changes in cognitive function. METHODS We performed a prospective assessment of 39 CAS patients, all of whom were right-handed. Patients with contralateral stenotic lesions were excluded. Twenty-one patients underwent CAS of the right internal carotid artery (Right CAS group) and 18 underwent CAS of the left internal carotid artery (Left CAS group). Neuropsychological testing was performed preoperatively and 6 months after endovascular treatment. Cerebral blood flow was determined by 123I-labeled N-isopropyl-p-iodoamphetamine single-photon emission computed tomography before and 6 months after CAS. RESULTS In the Right CAS group, postoperative performance intelligence quotient score (91.1±18.2) was significantly improved compared with the preoperative score (84.9±16.7; P<.001). In the Left CAS group, postoperative verbal intelligence quotient score (104.0±18.8) was significantly higher than that before endovascular treatment (97.9±15.8; P<.005). Postoperative regional cerebral blood flow was not significantly different from that before endovascular treatment in either group. However, regional cerebrovascular reactivity of the treated side showed significant improvement after treatment. CONCLUSIONS Amelioration of cognitive function may be dependent on the side of revascularization. Performance intelligence quotient improved after CAS in patients with severe carotid artery stenosis on the right side. Verbal intelligence quotient also improved on the left side after endovascular treatment. These effects seemed to involve improvement in regional cerebrovascular reactivity by CAS.

Comparison of lumbar drainage and external ventricular drainage for clearance of subarachnoid clots after Guglielmi detachable coil embolization for aneurysmal subarachnoid hemorrhage.

OBJECTIVE Subarachnoid clots play an important role in development of delayed vasospasm after subarachnoid hemorrhage (SAH). The purpose of this study was to compare clearance of subarachnoid clots using external ventricular drainage (EVD) or lumbar drainage (LD) after Guglielmi detachable coil (GDC) embolization for aneurysmal SAH. METHODS The subjects were 51 treated with GDC coil embolization for aneurysmal Fisher group 3 SAH within 72 h of ictus. Software-based volumetric quantification of the subarachnoid clots was performed on CT scans and the hemoglobin (Hb) level was measured in CSF drained from each catheter. RESULTS Clearance of subarachnoid clots was more rapid in patients treated with LD (n=34) compared to those treated with EVD (n=17). The Hb level in CSF was significantly higher in the LD group on Days 4-5 after onset of SAH (P<0.05), but was higher in the EVD group on Days 8-9. The incidence of symptomatic vasospasm did not differ between the two groups. The rate of occurrence of a new low density area on CT scans was higher in patients treated with EVD, but not significantly higher than the rate in the LD group. CONCLUSION GDC embolization followed by lumbar drainage accelerates the reduction of subarachnoid clots, but EVD may contribute to stasis of hemorrhage within subarachnoid spaces.

Cerebral hemodynamic benefits after contralateral carotid artery stenting in patients with internal carotid artery occlusion.

SUMMARY: CEA contralateral to an ICA occlusion is considered a surgical risk, and CAS may be an alternative for these patients. Our goal was to examine whether CAS improves cerebral hemodynamics on the treated side and on the side of the ICA occlusion, on the basis of measurement of CBF and CVR by using SPECT. The subjects were 8 patients who underwent contralateral CAS. Resting CBF and CVR to acetazolamide were measured by using 123I-IMP SPECT before and chronically (3–6 months) after CAS. Resting CBF was also measured immediately (<2 hours) after CAS by using 123I-IMP SPECT. There were no significant differences in resting CBF in both hemispheres immediately after CAS. However, resting CBF and CVR both significantly increased in the chronic period in both hemispheres. Contralateral CAS in patients with ICA occlusion resulted in cerebral hemodynamic improvement on the treated side and on the side of ICA occlusion.

Reproducibility of cerebral blood flow assessment using a quantitative SPECT reconstruction program and split-dose 123I-iodoamphetamine in institutions with different γ-cameras and collimators.

Single photon emission computed tomography (SPECT) is used widely in clinical studies. However, the technique requires image reconstruction and the methods for correcting scattered radiation and absorption are not standardized among SPECT procedures. Therefore, quantitation of cerebral blood flow (CBF) may not be constant across SPECT models. The quantitative SPECT (QSPECT) software package has been developed for standardization of CBF. Using the QSPECT/dual-table autoradiographic (DTARG) method, CBF and cerebral vascular reactivity (CVR) at rest and after acetazolamide challenge can be evaluated using 123I-iodoamphetamine in a single SPECT session. In this study, we examined the reproducibility of quantitative regional CBF and CVR in QSPECT/DTARG using different SPECT models at two facilities. The subjects were nine patients with chronic cerebral ischemic disease who underwent QSPECT/DTARG at both facilities with use of different γ-cameras and collimators. There were significant correlations for CBF at rest and after acetazolamide challenge measured at the two facilities. The consistency of the CBFs of the patients measured at the two facilities were good in all cases. Our results show that CBF measured by QSPECT/DTARG in the same patients is reproducible in different SPECT models. This indicates that standardized evaluation of CBF can be performed in large multicenter studies.

Intravenous thrombolysis with recombinant tissue plasminogen activator in a stroke patient treated with rivaroxaban.

As limited amounts of data are available regarding thrombolytic therapy for patients taking novel oral anticoagulants, thrombolytic therapy is not recommended in such cases. Here, we report an acute stroke patient taking rivaroxaban who received intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA). An 80-year-old man with a history of nonvalvular atrial fibrillation, who had been receiving 10 mg of rivaroxaban showed abrupt onset of aphasia and right hemiparesis. National Institutes of Health Stroke Scale score was 10. Onset of neurologic deficits occurred 4 hours after the last dose of rivaroxaban. Clinical data on admission were as follows: blood pressure, 170/90 mm Hg; prothrombin time (PT), 22.6 seconds (control, 12.9 seconds); international normalized ratio, 2.03; activated partial thromboplastin time, 46 seconds (normal, 23-32 seconds); and creatinine level, 1.11 mg/dL. Magnetic resonance angiography revealed occlusion of the superior trunk of the left middle cerebral artery. Intravenous infusion of .6 mg/kg of rt-PA (total dose, 36 mg) was performed 6 hours after the last rivaroxaban administration with informed consent. The neurologic deficit improved during infusion of rt-PA. Repeat brain computed tomography showed left frontal cortical infarction without hemorrhagic changes. In the case of rivaroxaban, it is difficult to accurately determine the drug activity. As the anticoagulant activity of rivaroxaban can be estimated from its pharmacokinetics and PT, it is clinically important to obtain accurate information about the timing of medication and blood sampling.

Intra-operative monitoring of lower extremity motor-evoked potentials by direct cortical stimulation.

OBJECTIVE Motor-evoked potentials (MEPs) are commonly recorded from upper-extremity muscles, whereas lower-extremity MEP (LE-MEP) monitoring has not been adequately established. The goal of the study was to develop a MEP monitoring method using direct cortical stimulation (DCS) for predicting motor deficits of lower extremities. METHODS Intra-operative LE-MEP monitoring was performed in 22 patients. After craniotomy, a subdural electrode was placed on the cortex so that the optimal contact was positioned 2 cm lateral from the midline on the motor cortex. The electrodes for stimulation consisted of a cathode at Fpz and an anode at the optimal contact site on the motor cortex. After stimulation was performed with short trains of five stimuli, LE-MEPs were recorded from the lower-limb muscles. RESULTS LE-MEPs were consistently recorded in all patients. Disappearance or amplitude reduction of MEP waveforms was observed in five patients, but the MEP waveforms had recovered and remained at the control level by dural closure, and no permanent motor deficit was observed in any patient. CONCLUSIONS We accomplished LE-MEP recording during supratentorial surgery using monopolar DCS with a subdural electrode placed on the convex side of the motor cortex. SIGNIFICANCE A useful method of intra-operative LE-MEP recording was described.

A novel trigger for cholesterol-dependent smooth muscle contraction mediated by the sphingosylphosphorylcholine-Rho-kinase pathway in the rat basilar artery: a mechanistic role for lipid rafts.

Hyperlipidemia is a risk factor for abnormal cerebrovascular events. Rafts are cholesterol-enriched membrane microdomains that influence signal transduction. We previously showed that Rho-kinase-mediated Ca2+ sensitization of vascular smooth muscle (VSM) induced by sphingosylphosphorylcholine (SPC) has a pivotal role in cerebral vasospasm. The goals of the study were to show SPC-Rho-kinase-mediated VSM contraction in vivo and to link this effect to cholesterol and rafts. The SPC-induced VSM contraction measured using a cranial window model was reversed by Y-27632, a Rho-kinase inhibitor, in rats fed a control diet. The extent of SPC-induced contraction correlated with serum total cholesterol. Total cholesterol levels in the internal carotid artery (ICA) were significantly higher in rats fed a cholesterol diet compared with a control diet or a β-cyclodextrin diet, which depletes VSM cholesterol. Western blotting and real-time PCR revealed increases in flotillin-1, a raft marker, and flotillin-1 mRNA in the ICA in rats fed a cholesterol diet, but not in rats fed the β-cyclodextrin diet. Depletion of cholesterol decreased rafts in VSM cells, and prevention of an increase in cholesterol by β-cyclodextrin inhibited SPC-induced contraction in a cranial window model. These results indicate that cholesterol potentiates SPC-Rho-kinase-mediated contractions of importance in cerebral vasospasm and are compatible with a role for rafts in this process.

Changes in glutamate concentration, glucose metabolism, and cerebral blood flow during focal brain cooling of the epileptogenic cortex in humans.

Recently, focal brain cooling (FBC) was proposed as a method for treating refractory epilepsy. However, the precise influence of cooling on the molecular basis of epilepsy has not been elucidated. Thus the aim of this study was to assess the effect of FBC on glutamate (Glu) concentration, cerebral blood flow (CBF), and glucose metabolism in patients with intractable epilepsy.