Ichiro Nakagawa

Clinical features of postoperative cerebral venous infarction

SummaryThere is a potential risk of sacrificing the cortical vein during neurosurgical operations, particularly in the interhemispheric or subtemporal approach. An impaired cortical vein might cause cerebral venous circulatory disturbances (CVCDs) resulting in venous infarction. In this article, we have reviewed the management and results of eight cases with symptomatic postoperative venous infarction.We have encountered eight cases with symptomatic postoperative venous infarction (0.3%) during the past 5 years. The series is composed of 3 males and 5 females, with ages that ranged from 43 to 76 years (mean age of 58.1 years), and consisted of five brain tumors, one cavernoma, one dural AVF, and one trigeminal neuralgia. Initial symptoms occurred intra-operatively in two, on 0 day after the operation in one, 1 day in three, 3 days in one, and 4 days in one case. The symptoms were intra-operative brain edema in two cases, disorientation in one, cerebellar signs in one, hemiparesis in one, aphasia in two, and headache in one case. Two cases required surgical intervention. The results were a good outcome in 6 and a fair outcome in 2 cases.In conclusion, there are two types of postoperative venous infarction; severe onset (severe type) and gradual onset (mild type). The former needs immediate treatment from the intra-operative period onward, and the prevention of the ongoing venous thrombosis is essential in the latter.

ATP-dependent potassium channel mediates neuroprotection by chemical preconditioning with 3-nitropropionic acid in gerbil hippocampus.

Chemical preconditioning with low dose of 3-nitropropionic acid (3-NPA) prolongs the latency to hypoxic depolarization (HD), which triggers cell death, and also restores the synaptic transmission which disappears during hypoxia in gerbil hippocampal slices. Here we show that these neuroprotective effects are mediated by the activation of K(ATP) channels. Diazoxide, a K(ATP) channel opener, prolonged the latency to HD dose-dependently to the same extent as that of the chemical preconditioning with 3-NPA. Glibenclamide, a K(ATP) channel blocker, abrogated the prolongation of HD with 3-NPA. The hypoxic tolerance of synaptic transmission with 3-NPA was also abolished by glibenclamide. Diazoxide also induced the hypoxic tolerance of synaptic transmission. Theses results suggest that K(ATP) channel is involved in the neuroprotection afforded by the chemical preconditioning.

Early Inhibition of Natriuresis Suppresses Symptomatic Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage

Background: Hyponatremia is a common complication occurring in one third of patients after subarachnoid hemorrhage (SAH). One mechanism that likely mediates the development of hyponatremia in SAH is cerebral salt wasting syndrome (CSWS), which induces natriuresis and reduces total blood volume, resulting in a risk of symptomatic vasospasm (SVS). The mineral corticoid fludrocortisone acetate enhances sodium reabsorption in the renal distal tubules and may help prevent post-SAH hyponatremia. However, management with fludrocortisone acetate is ineffective if hyponatremia is advanced, because CSWS and subsequent SVS develop rapidly. Therefore, an additional earlier marker is required to predict the development of hyponatremia for the initiation of immediate treatment in select patients. However, no conclusive evidence exists showing that hyponatremia influences the risk of SVS, and no standard treatment protocol exists for treating hyponatremia in patients with SAH. This study was undertaken to evaluate whether selective early treatment of hyponatremia prevents SVS in patients with increased urinary sodium excretion in the early phase following SAH. Methods: A total of 103 patients with aneurysmal SAH were managed for a postoperative electrolyte disorder after aneurysmal clipping or coil embolization. Between 2004 and 2007 (period 1), 54 patients started treatment to correct the electrolyte disorder after hyponatremia had occurred. Between 2007 and 2011 (period 2), 49 patients were prospectively subjected to sodium replacement treatment according to their daily sodium balance, and inhibition of natriuresis with fludrocortisone acetate was initiated just after an increase in urinary sodium excretion >300 mEq/day. The occurrence of hyponatremia, SVS, and outcomes were compared between the two periods. Results: Hyponatremia was observed in 14 patients (26%) in period 1 and 7 patients (14%) in period 2. The incidence of fludrocortisone acetate administration was significantly higher, and initiation of electrolyte correction was significantly earlier, in period 2 patients. We observed a significant difference in the frequency of SVS, which occurred in 10 patients (18.5%) in period 1 and 3 patients (6.1%) in period 2. Both urinary sodium excretion and urine volume at day 7 were significantly different between the two periods. However, no significant difference was observed in overall outcome between the two periods. Conclusions: Early inhibition of natriuresis with fludrocortisone acetate before the occurrence of hyponatremia prevented SVS after aneurysmal SAH. Increased urinary sodium excretion in the early phase of SAH is a good indicator for the initiation of electrolyte correction with fludrocortisone acetate.

Discriminant analysis prediction of the need for ventriculoperitoneal shunt after subarachnoid hemorrhage.

Shunt operations have conventionally been performed to deal with normal-pressure hydrocephalus after subarachnoid hemorrhage. The indication and timing of shunt operations are often based on clinical symptoms and head computed tomography findings, and the early identification of the need for such surgery would be advantageous. The present study examined whether this need could be predicted solely on the basis of data collected on patient admission. A total of 120 consecutive patients with subarachnoid hemorrhage who underwent radical surgery for aneurysm were analyzed for potential risk factors for the onset of hydrocephalus that could be investigated on admission. Statistically significant differences between those patients who required a shunt operation and those who did not were found in terms of age, Hunt and Kosnik grade on first visit, Glasgow Coma Scale score on first visit, Fisher group, presence/absence of hydrocephalus, presence/absence of intraventricular hemorrhage, and transverse dimension of the third ventricle and distance between lateral ventricles measured by head computed tomography scan on first visit. Discriminant analysis performed on these 8 variables yielded a single discriminant function with a high sensitivity of 85.3% and a high specificity of 87.2%. Our findings indicate that the discriminant function is capable of predicting the need for the shunt operation soon after patient admission and can shorten the waiting time for the operation, and hence can be expected to contribute to decreasing the length of hospital stay in these patients.

The use of susceptibility-weighted imaging as an indicator of retrograde leptomeningeal venous drainage and venous congestion with dural arteriovenous fistula: diagnosis and follow-up after treatment.

BACKGROUND Retrograde leptomeningeal venous drainage (RLVD) in dural arteriovenous fistulas (DAVFs) is associated with intracerebral hemorrhage and nonhemorrhagic neurological deficits or death. Angiographic evidence of RLVD is a definite indication for treatment, but less invasive methods of identifying RLVD are required. OBJECTIVE To evaluate the efficacy of susceptibility-weighted magnetic resonance imaging (SWI) in detecting RLVD in DAVFs. METHODS We retrospectively identified 17 DAVF patients who had angiographic evidence of RLVD and received treatment. Conventional angiography and SWI were assessed at pretreatment and posttreatment time points. The presence of RLVD on SWI was defined as cortical venous hyperintensity, and the presence of venous congestion on SWI venograms was defined as increased caliber of cortical or medullary veins. RESULTS Cortical venous hyperintensity was identified in pretreatment SWI of 15 patients. Cortical venous hyperintensity was absent in early posttreatment SWI, consistent with the absence of RLVD in posttreatment angiography, in all but one of these patients. In 2 patients, cortical venous hyperintensity was identified during follow-up, indicating the recurrence of RLVD. Cortical venous hyperintensity was not identified in the pretreatment SWI of 2 patients despite angiographic evidence of RLVD. Venous congestion was identified in pretreatment SWI venograms of 11 patients and had an appearance similar to that identified from angiography. Venous congestive signs improved over the follow-up period. CONCLUSION The presence of SWI hyperintensity within the venous structure could be a useful indicator of RLVD in DAVF patients. Thus, SWI offers a noninvasive alternative to angiography for the identification of RLVD in pretreated and posttreated DAVF patients.

Chemical preconditioning prevents paradoxical increase in glutamate release during ischemia by activating ATP-dependent potassium channels in gerbil hippocampus.

Ischemic tolerance induced by pretreatment with a low dose of 3-nitropropionic acid (3-NPA), called chemical preconditioning, prolongs the delay to hypoxic depolarization and improves the recovery of synaptic transmission (Exp. Neurol. 166 (2000), 385-391). We studied the effect of chemical preconditioning on the presynaptic site by analyzing spontaneous excitatory postsynaptic currents (sEPSCs) and miniature EPSCs (mEPSCs) with a whole cell patch-clamp technique in gerbil hippocampal slices. The frequency of sEPSCs decreased first and then dramatically increased during ischemia (10 min in duration, low pO(2), and deprivation of glucose) up to 200-300%. This increase was apparently a paradox, since synaptic transmission evoked by electrical stimulation diminished when the sEPSC frequency started to increase. The frequency of mEPSCs also increased in the same time course. Increases in sEPSC and mEPSC frequencies were prevented by chemical preconditioning with 3-NPA (4 mg/kg) administered intraperitoneally 3 h before the preparation of brain slices. These effects of chemical preconditioning were abolished by glibenclamide (5 microM), a blocker of ATP-dependent potassium (K(ATP)) channels, applied in vitro before the ischemic insult. The application of diazoxide (500 microM), an opener of K(ATP) channels, produced the same preventive effects on sEPSC and mEPSC frequencies. These results suggested that chemical preconditioning acted on presynaptic terminals to prevent the paradoxical increase in glutamate release during ischemia through the activation of K(ATP) channels.

Platelet inhibition by adjunctive cilostazol suppresses the frequency of cerebral ischemic lesions after carotid artery stenting in patients with carotid artery stenosis

OBJECTIVE Optimal platelet inhibition is an important therapeutic adjunct in patients with carotid artery stenosis undergoing carotid artery stenting (CAS). Clopidogrel resistance is associated with increased periprocedural thromboembolic complications from neurovascular stent placement procedures. The addition of cilostazol to dual antiplatelet therapy (DAT) has been reported to reduce platelet reactivity and to improve clinical outcomes after percutaneous coronary intervention. This study was undertaken to evaluate the impact of adjunctive cilostazol in patients with CAS. METHODS Platelet function was assessed by light transmittance aggregometry using the VerifyNow assay. Sixty-four consecutive patients who underwent CAS received standard DAT, clopidogrel (75 mg daily), and aspirin (100 mg daily) more than 4 weeks before the procedure. From 2010 to 2011 (period I), 28 patients underwent CAS under standard DAT. From 2011 to 2013 (period II), 36 patients prospectively had preoperative assessment of platelet function, and 13 patients with clopidogrel resistance received adjunctive cilostazol (200 mg daily) in addition to standard DAT. The incidence of new ipsilateral ischemic lesions on diffusion-weighted imaging a day after CAS and ischemic or hemorrhagic events within 30 days was assessed. RESULTS Clopidogrel resistance was indentified in 12 patients (43%) in period I and 13 patients (36%) in period II (P = .615). In period II, the addition of cilostazol significantly decreased P2Y12 reaction units and % inhibition (P = .006 and P = .005, respectively), and there was a significant difference in P2Y12 reaction units between the two periods. New ipsilateral ischemic lesions were significantly decreased in period II (2/36 patients) compared with period I (7/28 patients; P = .034); however, there was no significant difference in hemorrhagic and thromboembolic events between the two periods. CONCLUSIONS Adjunctive cilostazol (triple antiplatelet therapy) in clopidogrel-resistant patients reduces the rate of clopidogrel resistance and suppresses new ischemic lesions without hemorrhagic complications, as compared with standard DAT. Antiplatelet management based on the evaluation of antiplatelet resistance would be required for prevention of perioperative thromboembolic complications in CAS.

Initial experience of using the filter protection device during carotid artery stenting in Japan

Purpose No filter protection devices for carotid artery stenting (CAS) have been formally approved for use in Japan; however, as of April 2008, the Angioguard XP (AGXP) was approved. This article describes our initial results using the AGXP during CAS for the treatment of carotid artery stenosis.

Influence of Diabetes Mellitus and Cigarette Smoking on Variability of the Clopidogrel-Induced Antiplatelet Effect and Efficacy of Active Management of the Target P2Y12 Reaction Unit Range in Patients Undergoing Neurointerventional Procedures

BACKGROUND Optimal antiplatelet inhibition is essential in patients undergoing neurointerventional procedures; however, variability in response to clopidogrel can contribute to thromboembolic and hemorrhagic complications. The present study evaluated the influence of diabetes mellitus and cigarette smoking on clopidogrel reactivity. METHODS Between 2011 and 2013, 71 consecutive patients underwent aneurysmal coil embolization (CE) or carotid artery stenting (CAS) and received clopidogrel (75 mg daily) and aspirin (100 mg daily) before the treatment. The patients were divided into 2 groups: CE (n = 31) and CAS (n = 40). The patients underwent prospective assessment of preoperative platelet function using VerifyNow assay and received adjunctive cilostazol (200 mg daily, triple antiplatelet therapy) in case of clopidogrel hyporesponse. Patients with clopidogrel hyper-response underwent clopidogrel dose reduction (clopidogrel, 12.5-50 mg daily). RESULTS Clopidogrel resistance was noted in 15 patients (37.5%) in the CAS group and in 4 patients (12.9%) in the CE group (P = .031). Clopidogrel hyper-response was noted in 2 patients (5%) in the CAS group and in 11 patients (54.8%) in the CE group (P < .001). There was a significant difference in the baseline clinical characteristics between the 2 groups. In the multivariate logistic regression analysis, diabetes and age were independent predictors of clopidogrel hyporesponse, whereas current smoker was an independent predictor of clopidogrel hyper-response. CONCLUSIONS Significant differences in baseline clinical characteristics were present when comparing patients undergoing endovascular treatment of unruptured cerebral aneurysms and carotid artery stenosis. Diabetes mellitus and current smoker status were independent factors related to reactivity to clopidogrel.

The neuroprotective effect of diazoxide is mediated by mitochondrial ATP-dependent potassium channels in a rat model of acute subdural hematoma

Acute subdural hematoma (ASDH) results in neuronal death due to mitochondrial dysfunction and a subsequent cascade of apoptotic and necrotic events. We previously demonstrated that mitochondrial ATP-dependent potassium (mitoK(ATP)) channels have a major role in cerebral ischemic preconditioning in vivo and in vitro. However, the role of the mitoK(ATP) channel has not been investigated in the context of ASDH. Thus, the purpose of this study was to determine whether the mitoK(ATP) channel mediates neuroprotection in a rat model of ASDH. Male Wistar rats were subjected to subdural infusion of 400 μL autologous venous blood. The rats were assigned to four experimental groups pretreated intraventricularly 15 minutes before ASDH with (1) vehicle (n=10); (2) the mitoK(ATP) channel agonist diazoxide (n=9); (3) diazoxide plus the selective mitoK(ATP) channel antagonist 5-hydroxydecanoate (5-HD) (n=6); or (4) 5-HD alone (n=6). Infarct volume was assessed at 4 days after ASDH. Brain edema formation was also measured. Pretreatment with diazoxide significantly reduced infarct volume and brain edema formation after ASDH. However, the effects of diazoxide were abolished by co-treatment with 5-HD. 5-HD alone increased infarct volume. These data suggest that the mitoK(ATP) channel is an important mediator of the neuroprotective effects of cerebral preconditioning in a rat model of ASDH.