The Effect of Aging on Nitric Oxide Production during Cerebral Ischemia and Reperfusion in Wistar Rats and Spontaneous Hypertensive Rats: An In Vivo Microdialysis Study.

Nitric oxide (NO) is involved in the pathogenesis of cerebral ischemic injury. Here, we investigated the effects of aging on NO production during cerebral ischemia-reperfusion (IR). Male Wister rats (WRs) were assigned to 12-month-old (older; n = 5) and 3-month-old (younger; n = 7) groups. Similarly, male spontaneous hypertensive rats (SHRs) were allocated to 12-month-old (older; n = 6) and 3-month-old (younger; n = 8) groups. After anesthesia, their NO production was monitored using in vivo microdialysis probes inserted into the left striatum and hippocampus. Forebrain cerebral IR injuries were produced via ligation of the bilateral common carotid arteries, followed by reperfusion. The change in the NO3- of the older rats in the SHR groups in the striatum was less compared to that of the younger rats before ischemia, during ischemia, and after reperfusion (p < 0.05). In the hippocampus, the change in the NO3- of the older rats in the SHR groups was lower compared to that of the younger rats after reperfusion (p < 0.05). There were no significant differences between the two WR groups. Our findings suggested that aging in SHRs affected NO production, especially in the striatum, before and during cerebral ischemia, and after reperfusion. Hypertension and aging may be important factors impacting NO production in brain IR injury.

Progressive Bilateral Vertebral Artery Dissection in a Case of Osteogenesis Imperfecta.

A 32-year-old woman with osteogenesis imperfecta (OI) was admitted to the hospital because of a right-sided occipital headache and facial paresthesia. She was diagnosed with lateral medullary syndrome due to right vertebral artery (VA) dissection. She was treated conservatively without antithrombotic therapy. She developed subarachnoid hemorrhage because of contralateral VA dissection 18 days later. This clinical course may reflect the underlying weakness of the vessel wall in OI. In patients with OI, occlusion of a unilateral VA could cause dissection and subsequent rupture of the contralateral VA. Early surgical treatment for lesions of the VA is required in such cases.

Prediction of ischemic stroke in patients with tissue-defined transient ischemic attack.

BACKGROUND: The risk of future stroke after transient ischemic attack (TIA) has been widely studied, but most findings were obtained for classically defined TIA (time-defined TIA). A new definition of TIA, that is, tissue-defined TIA, which requires the absence of fresh brain infarction on magnetic resonance imaging, could change stroke risk assessments. We, therefore, aimed to evaluate the risk of future stroke in patients with tissue-defined TIA. METHODS: We retrospectively reviewed 74 patients with tissue-defined TIA, who could be followed for 2 years. Clinical, laboratory, and radiological data were collected and compared between groups that did and did not develop ischemic stroke within the 2-year period. RESULTS: Ischemic stroke occurred in 11 patients (14.9%). Increased age, hemiparesis, and/or dysarthria during the TIA, old cerebral infarction revealed by magnetic resonance imaging, and large-artery stenosis detected by magnetic resonance angiography and/or ultrasonography tended to increase the risk of future stroke, but no individual factor showed statistically significant effect. TIA etiology did not significantly affect the risk. ABCD2 score, an established score for predicting stroke after time-defined TIA, showed only a weak association with future stroke. In contrast, new scores that we created reliably predicted future stroke; these included the APO (age, paresis, and old cerebral infarction) and APOL (age, paresis, old cerebral infarction, and large-artery stenosis) scores. The areas under the receiver operating characteristic curves were .662, .737, and .807 for ABCD2, APO, and APOL, respectively. CONCLUSIONS: Compared with the established measures, our newly created scores could predict future stroke for tissue-defined TIA more reliably.

The CHA(2)DS(2)-VASc score reflects clinical outcomes in nonvalvular atrial fibrillation patients with an initial cardioembolic stroke.

BACKGROUND: Whether the CHA(2)DS(2)-VASc score reflects severity or clinical outcomes in patients with an initial cardioembolic stroke associated with nonvalvular atrial fibrillation (NAVF) was investigated. METHODS: This study included 327 patients hospitalized between April 2007 and March 2012 for an initial cardioembolic stroke associated with NVAF with no history of stroke. The National Institutes of Health Stroke Scale (NIHSS) score on admission and clinical outcome (modified Rankin Scale [mRS] score after 90 days) were retrospectively evaluated according to the CHA(2)DS(2)-VASc score. RESULTS: CHA(2)DS(2)-VASc scores were 0, 3.1%; 1, 9.1%; 2, 24.5%; 3, 26%; 4, 20.8%; 5, 14.4%; and 6, 2.1%. The median NIHSS scores for CHA(2)DS(2)-VASc scores of 0-6 were 4.5, 8, 8, 10, 11, 17, and 23, respectively. Severity differed according to the CHA(2)DS(2)-VASc score. The clinical outcomes according to the CHA(2)DS(2)-VASc scores were as follows: score 0, mRS scores of 0-2 (80%) and 3-6 (20%); score 1, mRS scores of 0-2 (80%) and 3-6 (20%); score 2, mRS scores of 0-2 (64%) and 3-6 (36%); score 3, mRS scores of 0-2 (48%) and 3-6 (52%); score 4, mRS scores of 0-2 (28%) and 3-6 (72%); score 5, mRS scores of 0-2 (26%) and 3-6 (74%); and score 6, mRS scores of 0-2 (29%) and 3-6 (71%). The clinical outcome worsened as the CHA(2)DS(2)-VASc score increased. On logistic regression analysis, age, NIHSS score on admission, and thrombolytic therapy were related to a clinical outcome. CONCLUSIONS: The severity of NVAF-induced initial cardioembolic stroke increased with higher CHA(2)DS(2)-VASc scores, and the outcomes were poor. The present study suggests that the CHA(2)DS(2)-VASc score may be useful not only for the evaluation of stroke risk but also for the prediction of clinical outcomes after stroke.

Treatment outcomes of tissue plasminogen activator infusion for branch atheromatous disease.

BACKGROUND: The objective of this study was to evaluate treatment outcomes of tissue plasminogen activator (t-PA) infusion for hyperacute branch atheromatous disease (BAD) within 3 hours after onset. METHODS: A total of 152 BAD patients with lenticulostriate artery (LSA) or paramedian pontine artery (PPA) territory infarcts (LSA 114; PPA 38) were hospitalized between April 2007 and June 2012. Of these, 21 BAD patients (LSA 19; PPA 2) arrived at the hospital within 3 hours after onset, and, among these, 8 patients who received t-PA infusion (.6 mg/kg) were included in this study. All BAD patients who received t-PA infusion had LSA territory infarcts. RESULTS: Six of 8 patients (75%) had improvement of neurologic findings within 60 minutes after t-PA infusion, but neurologic findings deteriorated within 24 hours in 4 of these patients (67%). In all patients with deterioration, diffusion-weighted imaging after 24 hours revealed infarct expansion. One patient (13%) had symptomatic intracranial hemorrhage. After 3 months, the modified Rankin Scale (mRS) score was 0 to 2 in 6 patients (75%) and 3 to 6 in 2 patients (25%). CONCLUSIONS: With t-PA infusion for BAD, symptoms transiently improved, but the rate of symptom deterioration was high. The outcome after 3 months was relatively good.

Additional endovascular therapy in patients with acute ischemic stroke who are nonresponsive to intravenous tissue plasminogen activator: usefulness of magnetic resonance angiography-diffusion mismatch.

BACKGROUND: In patients who are not responsive to intravenous tissue plasminogen activator (IV t-PA), the present study aimed to report recanalization rates, the incidence of hemorrhagic transformation (HT), and clinical outcomes of additional endovascular therapy (AET), and to investigate the usefulness of magnetic resonance angiography-diffusion mismatch (MDM) in a selection of patients eligible for AET. METHODS: Fifty-eight patients who received IV t-PA therapy because of intracranial major artery occlusion between April 2007 and November 2010 were divided into 2 groups: 18 patients in the AET group and 21 patients in the IV t-PA nonresponders group. The remaining 19 patients were responders to IV t-PA and therefore not eligible for this study. Recanalization rates, HT incidence, and 3-month outcomes were assessed, and the relationship between MDM and clinical outcome was examined. RESULTS: A 3-month modified Rankin Scale (mRS) score of 0 to 3 was seen more frequently in the AET group (72% in the AET group v 29% in the nonresponder group; P = .01). Serious outcomes (3-month mRS of 5-6) were seen significantly less often in the AET group (17%) than in the nonresponder group (57%; P = .019). There were no differences in the incidence of HT. In the AET group, reappraisal considering MDM revealed a significantly higher rate of a 3-month mRS of 0 to 3 in the MDM-positive group compared to the MDM-negative group (86% v 25%, respectively; P = .044). Serious outcomes were observed significantly less frequently in the MDM-positive group compared to the MDM-negative group (0% v 75%, respectively; P = .005). CONCLUSIONS: AET for nonresponders to IV t-PA was safe, improved recanalization rates, and led to better prognoses. MDM was a very good predictor of improved prognosis in a selection of eligible patients for AET after IV t-PA.

Clinical review of 28 patients with basilar artery occlusion.

BACKGROUND: We retrospectively analyzed factors related to the outcomes of patients with basilar artery occlusion. METHODS: Twenty-eight patients with basilar artery occlusion admitted to our hospital within 24 hours after onset between April 2007 and December 2010 were included. We investigated parameters related to outcome, such as coexisting disease, clinical type, clinical severity at admission, the site of occlusion and the infarction lesion, the collateral flow from posterior communicating artery, therapy, and time to therapy after onset. RESULTS: Of 28 patients with basilar artery occlusion, good outcomes occurred in 6 patients (21%) and poor outcomes occurred in 22 patients (79%). Clinical severity on admission was significantly different between the 2 groups. Three of 5 patients with percutaneous transluminal angioplasty achieved recanalization. Two of 3 cases with recanalization resulted in poor outcomes. CONCLUSIONS: Clinical severity on admission was the determinant factor of functional prognosis in patients with basilar artery occlusion.

Magnetic resonance imaging investigation of secondary degeneration of the mesencephalic substantia nigra after cerebral infarction.

Secondary degeneration of the mesencephalic substantia nigra after cerebral infarction is widely known to occur in animal experiments, but has yet to be sufficiently investigated in human cerebral infarction. This study investigated the background and features of patients exhibiting secondary degeneration of the mesencephalic substantia nigra. The subjects comprised 43 patients admitted to our hospital for cerebral infarction between April 2007 and October 2010 showing secondary degeneration of the mesencephalic substantia nigra on cranial magnetic resonance imaging (MRI). We investigated clinical disease type, location of vascular occlusion, lesion site, and time from onset of symptoms to lesion identification by MRI. The clinical disease type was cardiogenic embolism in 29 patients (67%), atheromatous embolism (artery to artery) in 8 patients (19%), embolism (origin unknown) in 2 patients (5%), infarction after coil embolization for internal carotid aneurysm in 1 patient (2%), arterial dissection in 2 patients (5%), and vasculitis due to Takayasu disease in 1 patient (2%). Magnetic resonance angiography (MRA) identified the occluded vessel as the internal carotid artery in 19 patients (44%), the middle cerebral artery (M1) in 20 patients (47%), and the middle cerebral artery (M2) in 3 patients (7%); MRA was not performed in 1 patient (2%). The cerebral infarctions were striatal in 7 patients (16%) and striatal and cortical in 36 patients (84%). Hyperintense regions in the mesencephalic substantia nigra were observed in all patients after 7-28 days (mean, 13.3 days) on diffusion-weighted imaging or fluid-attenuated inversion recovery and T2-weighted MRI. Most patients with secondary degeneration of the substantia nigra demonstrated clinical disease comprising vascular occlusion of the internal carotid artery or the neighborhood of the middle cerebral artery, which was envisaged to cause a sudden drop in brain circulation across a wide area. Striatal infarctions were observed in all patients. Secondary degeneration of the substantia nigra appeared at 1-4 weeks after onset and disappeared after several months.

Significance of magnetic resonance angiography-diffusion weighted imaging mismatch in hyperacute cerebral infarction.

Therapeutic results with respect to lesion size were analyzed and compared in patients with hyperacute cerebral infarction with and without major artery lesions on magnetic resonance angiography (MRA) and in those who did and did not receive intravenous (IV) tissue plasminogen activator (t-PA). Of the patients with cerebral infarction who visited the hospital within 3 hours of onset between April 2007 and September 2009, 127 patients with cerebral infarction in the anterior circulation region in whom head magnetic resonance imaging (diffusion-weighted imaging [DWI]) or MRA was performed (81 men and 46 women; mean age, 71 ± 11 years) were enrolled. Major artery lesions (+) were defined as internal carotid artery occlusion and middle cerebral artery (M1/M2 segment) occlusion and ≥50% stenosis. Based on the presence or absence of major artery lesions and the size of DWI lesions, the subjects were divided into 3 groups: MRA-DWI mismatch (+) group [major artery lesion (+) and DWI-ASPECTS ≥6], MRA-DWI mismatch (-) group [major artery lesion (+) and DWI-ASPECTS <6], and major artery lesion (-) group. IV t-PA was given to 21 of the 64 patients in the MRA-DWI mismatch (+) group, to 1 of the 24 patients in the MRA-DWI mismatch (-) group, and to 9 of the 39 patients in the major artery lesion (-) group. In the MRA-DWI mismatch (+) group (n = 64), the median National Institutes of Health Stroke Scale (NIHSS) score on admission was higher in t-PA-treated patients than in t-PA-untreated patients (15 vs 11). The modified Rankin scale (mRS) score at day 90 after onset was more favorable in t-PA-treated patients (0-2 in 10 patients [48%] and 3-6 in 11 patients [52%]) than in t-PA-untreated patients (0-2 in 12 patients [28%] and 3-6 in 31 patients [72%]). After adjusting for admission NIHSS score, there was a significant difference in outcome (mRS score) between t-PA-treated patients (0-2 in 10 patients [48%] and 3-6 in 11 patients [52%]) and t-PA-untreated patients (0-2 in 3 patients [9%] and 3-6 in 29 patients [91%]) (P = .002). In the MRA-DWI mismatch (-) group (n = 24), mRS scores at day 90 after onset were poor in both t-PA-treated (3-6 in 1 patient [100%]) and t-PA-untreated patients (0-2 in 1 patient [4%] and 3-6 in 22 patients [96%]). In the major artery lesion (-) group (n = 39), mRS scores at day 90 after onset were favorable in both t-PA-treated (0-2 in 9 patients [100%]) and t-PA-untreated patients (0-2 in 28 patients [93%] and 3-6 in 2 patients [7%]). When comparing major artery lesions in the MRA-DWI mismatch (+) group, outcomes were more favorable in patients with M1/M2 segment lesions who received t-PA than in those who did not receive t-PA. In the MRA-DWI mismatch (+) group, the prognosis was significantly better for t-PA-treated patients than for t-PA-untreated patients, suggesting that IV t-PA is indicated in patients with MRA-DWI mismatch.

Relationship of obesity to recanalization after hyperacute recombinant tissue-plasminogen activator infusion therapy in patients with middle cerebral artery occlusion.

BACKGROUND: This was a retrospective analysis of factors related to recanalization after hyperacute recombinant tissue-plasminogen activator (rt-PA) infusion therapy in patients with middle cerebral artery occlusion. METHODS: Of the 50 patients (39 males and 11 females; mean age 70 ± 11 years) with cerebral infarction who were able to undergo diffusion-weighted magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) of the head within 24 hours of starting rt-PA infusion therapy while hospitalized at our center between April 2007 and October 2010, 23 patients (18 males and 5 females; mean age 71 ± 9.4 years) with hyperacute cerebral infarction with findings of obstruction in the proximal segment of the middle cerebral artery (MCA-M1) served as subjects. RESULTS: Of the 23 patients with MCA occlusion, 13 (57%) were recanalized. Analysis of factors related to recanalization revealed a significant difference (P = .019) for obesity (body mass index >25 kg/m(2)), with significantly more obese patients in the nonrecanalized group than in the recanalized group. The study revealed no significant differences in other factors between the 2 groups. CONCLUSIONS: The results suggest that obesity may be involved in recanalization after hyperacute rt-PA infusion therapy in patients with MCA occlusion.

Spontaneous cervicocephalic arterial dissection with headache and neck pain as the only symptom.

BACKGROUND AND OBJECTIVE: Cervicocephalic arterial dissection can cause both ischemic stroke and hemorrhagic stroke. However, spontaneous cervicocephalic arterial dissection presenting only with headache and neck pain has rarely been reported. The clinical features of patients with spontaneous cervicocephalic arterial dissection presenting only with headache and neck pain were investigated. METHODS: The subjects were seven patients with spontaneous cervicocephalic arterial dissection with headache and neck pain alone who were admitted to our hospital during the past 3 years. The clinical features of these patients were investigated. The diagnosis of arterial dissection was based on the criteria of the Strategies Against Stroke Study for Young Adults in Japan. RESULTS: The age of the patients (3 males, 4 females) ranged from 35 to 79 (mean, 51.0 ± 16.2) years. Six patients had vertebral artery dissection, one had internal carotid artery dissection, and one had an association of vertebral and internal carotid artery dissection. With the exception of one patient, the headache and neck pain were unilateral. All patients with vertebral artery dissection complained of posterior cervical or occipital pain. In the cases of internal carotid artery dissection, one patient complained of temporal pain, and one patient with co-existing vertebral artery dissection complained of posterior cervical pain. The mode of onset was acute in five patients, thunderclap in one, and gradual and progressive in one. The pain was severe in all cases. Five patients complained of continuous pain, while two had intermittent pain. The quality of the pain was described as throbbing by five patients and constrictive by two. The headache and neck pain persisted for 1 week or longer in six of the seven patients. CONCLUSION: Cervicocephalic arterial dissection should be suspected when patients complain of intense unilateral posterior cervical and occipital pain or temporal pain.

Significance of clinical-diffusion mismatch in hyperacute cerebral infarction.

In recent years, patient selection for intravenous tissue plasminogen activator (t-PA) therapy based on clinical-diffusion mismatch (CDM) has been closely examined. We investigated the relationship between prognosis and CDM in patients with hyperacute cerebral infarction within 3 hours of onset and compared CDM with diffusion-perfusion mismatch (DPM). Of 122 patients with hyperacute cerebral infarction who visited the hospital within 3 hours of onset between April 2007 and November 2008, 85 patients with cerebral infarction in the anterior circulation who underwent head magnetic resonance imaging diffusion-weighted imaging (DWI)/magnetic resonance angiography (MRA) (51 men and 34 women; average age, 74 ± 10 years) were enrolled. Seventeen of these patients underwent CT perfusion imaging. CDM-positive cases were those with a National Institute of Health Stroke Scale (NIHSS) score ≥ 8 and a DWI-Alberta Stroke Program Early CT Score (DWI-ASPECTS) ≥ 8; CDM-negative cases were those with an NIHSS score ≥ 8 and an ASPECTS-DWI < 8. The other patients were classified as belonging to the NIHSS score < 8 group. Of the 32 CDM-positive cases, 10 received t-PA infusion. These patients had markedly higher modified Rankin Scale scores 90 days after onset compared with the 22 patients who did not receive t-PA infusion. The 8 CDM-positive cases included 4 DPM-positive cases and 4 DPM-negative cases, and a discrepancy was confirmed between CDM and DPM. In all DPM-positive cases, MRA confirmed lesions in major intracranial arteries. CDM may enable more accurate prediction of outcomes in patients with hyperacute cerebral infarction. In addition, the combination of CDM findings and MRA findings (stenosis or occlusion in major intracranial arteries) may be an alternative to DPM for determining the indications for IV t-PA therapy in patients with hyperacute cerebral infarction.

[Locked-in syndrome due to bilateral cerebral peduncular infarctions with occlusion of persistent primitive trigeminal artery].

A 61-year-old woman with diabetes mellitus was admitted to our hospital with right hemiparesis and dysarthria. Brain MRI showed bilateral cerebral peduncular infarctions. Three days after admission, she was unable to generate any voluntary movements, except for those of the eye, suggesting locked-in syndrome (LIS). She could not speak, but showed good comprehension by blinking in response to verbal commands. Brain CT 5 days later revealed subarachnoid hemorrhage (SAH) around quadrigeminal and ambient cistern. Cerebral angiogram on the following day revealed no aneurysm, occlusion of right persistent primitive trigeminal artery (PPTA) and a little flow of the bilateral vertebral arteries. Eye movements were impossible in all directions on the 11th day and MRI showed new infarctions of the midbrain and the ventral portion of the pons. However, an EEG on the 20th day was almost normal. We speculated that low blood flow in the basilar artery from the PPTA caused bilateral cerebral peduncular infarctions, and that weakness of the PPTA caused SAH.

A peroxisome proliferator-activated receptor-gamma agonist reduces infarct size in transient but not in permanent ischemia.

BACKGROUND AND PURPOSE: Activators of peroxisome proliferator-activated receptor-gamma (PPARgamma), a member of the PPAR family, increase levels of CuZn-superoxide dismutase (SOD) in cultured endothelium, suggesting a mechanism by which it may exert its protective effect within the brain. These properties raise the question of whether a PPARgamma agonist may be neuroprotective in models of ischemia without reperfusion, in which oxidative injury is less prevalent. METHODS: In 2 groups of rats, 90 minutes of middle cerebral artery (MCA) occlusion was followed by 1 day of reperfusion, with 1 group receiving pioglitazone (a PPARgamma agonist) starting 72 hours before MCA occlusion (MCAO) and continuing through the day of occlusion, whereas the other group received vehicle only. In 2 comparable groups, the MCA was occluded permanently. One day after occlusion, the animals were tested neurologically and infarct volumes were calculated. In a separate group, rats were treated with pioglitazone or vehicle for 4 days. Tissue was obtained from the cortex and the striatum 2 hours into reperfusion after 90 minutes of MCAO, and the tissue was examined for CuZn-SOD by Western blot. RESULTS: Results show a significant reduction in infarct size in the treated rats, with transient MCAO but not permanent MCAO. There was also an improvement in neurological score in the treated animals after transient MCAO. The level of CuZn-SOD was increased in the cortex in treated animals. CONCLUSIONS: These data, which show that a PPARgamma agonist reduces infarct size in transient but not permanent MCAO, suggest that the role of PPARgamma is specific to events occurring during reperfusion. Our data point to CuZn-SOD as the mediator of this neuroprotection.

Dual antiplatelet therapy clopidogrel with low-dose cilostazol intensifies platelet inhibition in patients with ischemic stroke.

OBJECTIVE: We previously reported that the antiplatelet action is intensified with combined use of clopidogrel and cilostazol in ischemic stroke patients using the VerifyNow P2Y12 Assay. In this study, the relationship between the cilostazol dose and the platelet function achieved with combination therapy was investigated. METHODS: The subjects included 231 patients with noncardiogenic ischemic stroke treated at our hospital (18 patients treated with a combination of clopidogrel (75 mg) and cilostazol (100 mg), 52 patients treated with a combination of clopidogrel (75 mg) and cilostazol (200 mg), 126 patients treated with clopidogrel (75 mg) alone and 35 patients treated with cilostazol (200 mg) alone). The platelet function achieved with 20 µM of adenosine diphosphate was measured using the VerifyNow P2Y12 Assay. Clopidogrel resistance was defined as P2Y12 Reaction Units (PRU) >230 and/or % inhibition <20%. Results The PRU was >230 in 32 patients (25.4%) receiving clopidogrel alone, one patient (5.6%) receiving combination therapy with cilostazol (100 mg) and one patient (1.9%) receiving combination therapy with cilostazol (200 mg). The rate of PRU >230 was significantly lower in both of the cilostazol combination groups than in the clopidogrel alone group. The percent inhibition was <20% in 41 patients (32.5%) receiving clopidogrel alone, one patient (5.6%) receiving a combination with cilostazol (100 mg) and one patient (1.9%) receiving a combination with cilostazol (200 mg). The rate of % inhibition <20% was significantly lower in both of the cilostazol combination groups than in the clopidogrel alone group. CONCLUSION: Clopidogrel resistance was clearly decreased with combination clopidogrel (75 mg) and low-dose (100 mg) cilostazol therapy. The use of combination therapy with clopidogrel and low-dose cilostazol may be one means of overcoming clopidogrel resistance.

An adult case of pneumocephalus and pneumococcal meningitis associated with the sphenoid sinusitis.

A 60-year-old man was admitted to our hospital after being found at his home in a comatose state. Cerebrospinal fluid and blood cultures were positive for Streptococcus pneumoniae. Brain magnetic resonance imaging (MRI) revealed sinusitis in the sphenoid sinus. Computed tomography demonstrated the presence of multiple air pockets in the basilar cistern, and we diagnosed pneumococcal meningitis complicated with pneumocephalus. Multiple cerebral infarctions were found on brain MRI after admission. In this case, pneumocephalus was secondary to pneumococcal meningitis due to sinusitis on admission, and multiple cerebral infarctions after admission. We demonstrated that early diagnosis is required for the successful treatment of pneumococcal meningitis.

Clopidogrel resistance and the effect of combination cilostazol in patients with ischemic stroke or carotid artery stenting using the VerifyNow P2Y12 Assay.

OBJECTIVE: The inhibitory response to clopidogrel considerably varies among individuals and clopidogrel resistance is a risk factor for thrombotic events in patients with cardiovascular disease. Based on the platelet aggregation evaluated by the VerifyNow P2Y12 Assay, the present study investigated clopidogrel resistance and the effect of cilostazol addition. METHODS: We measured the ability of 20 µM ADP to aggregate platelets using the VerifyNow P2Y12 Assay. Clopidogrel resistance was defined as % inhibition of <20% in this assay. PATIENTS: We examined 77 patients (53 men and 24 women, aged 65.8 ± 9.9 years) with ischemic stroke or carotid artery stenting who received clopidogrel (75 mg) for >7 days at our hospital between October 2009 and March 2010. For 62 patients (42 men and 20 women, aged 65.3 ± 9.9 years) 75 mg clopidogrel alone was administered (clopidogrel only group); the other 15 patients (11 men and 4 women, aged 67.9 ± 9.9 years) received 75 mg of clopidogrel plus 100 or 200 mg of cilostazol (cilostazol combination group). RESULTS: Clopidogrel resistance was identified in 18 (29%) of the 62 patients in the clopidogrel only group. The percent inhibition was significantly higher in the cilostazol combination group than in the clopidogrel only group (41.7 ± 28.0% vs. 64.9 ± 22.7%, p=0.005). None of the patients in the cilostazol combination group had % inhibition of <20%. CONCLUSION: Clopidogrel resistance developed in 29% of patients given clopidogrel alone. The addition of cilostazol to clopidogrel may have intensified platelet inhibition.

Subarachnoid hemorrhage as the initial presentation of cerebral venous thrombosis.

Cerebral venous thrombosis presenting as subarachnoid hemorrhage (SAH) is very rare. We present a woman with thrombosis of the superior sagittal, straight, transverse and sigmoid sinuses who presented with SAH in the right temporal sulcus and bilateral cerebellar sulci. Brain perfusion CT demonstrated a delay of the mean transit time and high cerebral blood volume around the right posterior temporal lobe and cerebellum. These findings were compatible with venous congestion and they suggest the possibility that extension of the dural sinus thrombosis into the superficial veins caused localized venous hypertension with dilatation of the thin, fragile-walled cortical veins which eventually ruptured into the subarachnoid space.

Stroke as a manifestation of Takayasu's arteritis likely due to distal carotid stump embolism.

The clinical symptoms of Takayasu's arteritis (TA), which mainly affects the aorta and major aortic branches, vary widely depending on the site and degree of arterial lesions. We present herein the case of a young man whose initial symptom was pulmonary artery occlusion and who manifested TA 6 years later as cerebral embolism. Angiography confirmed bilateral common carotid artery (CCA) occlusion and a well-developed collateral circulation. The stump of the occluded CCA has both proximal and distal ends. The possibility of emboli from the occluded CCA (distal stump) seems to be the most probable explanation, as turbulent flow was detected at distal stump on color Doppler sonography. The carotid stump can be a potential source of emboli in TA as well as in atherosclerosis.

Nitric oxide production during cerebral ischemia and reperfusion in eNOS- and nNOS-knockout mice.

The purpose of this study was to clarify the kinetics of nitric oxide (NO) induced by either endothelial NO synthase (eNOS) or neuronal NO synthase (nNOS) after transient global forebrain ischemia. We investigated NO production and ischemic changes to hippocampal CA1 neurons in eNOS knockout (-/-) mice and nNOS (-/-) mice during cerebral ischemia and reperfusion. NO production was continuously monitored by in vivo microdialysis. Global forebrain ischemia was produced by occlusion of both common carotid arteries for 10 minutes. Levels of nitrite (NO(2)(-)) and nitrate (NO(3)(-)), as NO metabolites, in dialysate were determined using the Griess reaction. Two hours after the start of reperfusion, animals were perfused with 4% paraformaldehyde. Hippocampal CA1 neurons were divided into three phases (severely ischemic, moderately ischemic, surviving), and the ratio of surviving neurons to degenerated neurons was calculated as the survival rate. The relative cerebral blood flow (rCBF) was significantly higher in nNOS (-/-) mice than in control mice after reperfusion. Levels of NO(3)(-) were significantly lower in eNOS (-/-) mice and nNOS (-/-) mice than in control mice during ischemia and reperfusion. NO(3)(-) levels were significantly lower in nNOS (-/-) mice than in eNOS (-/-) mice after the start of reperfusion. Survival rate tended to be higher in nNOS (-/-) mice than in control mice, but not significantly. These in vivo data suggest that NO production in the striatum after reperfusion is closely related to activities of both nNOS and eNOS, and is mainly related to nNOS following reperfusion.