[A case of recurrent stroke with carotid-web despite dabigatran treatment successfully treated by carotid endarterectomy].

We present a case of a 41-year-old female presenting with recurrence of ischemic stroke on subtherapeutic doses of dabigatran. She had a history of embolic stroke of undetermined sources at the age of 40, and underwent implantable cardiac monitor implantation and had started dabigatran. One year after the first ischemic stroke, she presented with sudden dysarthria and left hemiparesis and was admitted to our hospital. An MRI of the head revealed acute cerebral infarction in the right corona radiata, and an MR angiography revealed right M2 occlusion. Cervical 3D-CTA revealed a protruding structure on the posterior wall of the carotid artery bulb, which was diagnosed as carotid web. She underwent carotid endarterectomy, and the specimen was pathologically confirmed to be vascular malformation due to fibromuscular dysplasia.

Intracranial vascular stenosis in giant cell arteritis successfully treated by two balloon angioplasty procedures.

Intracranial vascular stenosis is rarely associated with giant cell arteritis (GCA), and the prognosis for stroke caused by GCA is poor. Despite its unfavourable outcome, the strategy to manage this involvement and the indication of endovascular treatment are not well defined in the latest guidelines or recommendations. Here, we present a case in a 68-year-old woman, which was refractory to medical therapy, but successfully treated by two balloon angioplasty procedures. She was admitted to our department with lower extremity stiffness and left visual disturbance. GCA was clinically diagnosed by the wall thickening of the temporal artery and the aorta. Hemiparesis and motor aphasia developed shortly after intravenous methylprednisolone pulse therapy, and magnetic resonance imaging revealed acute cerebral infarction with severe stenosis at the end of the left internal carotid artery. Balloon angioplasty was tried initially with improvement in her symptoms and additionally performed to treat restenosis without any significant adverse events. Her symptoms markedly improved with no recurrence until 8 months after discharge. We also review 10 similar cases reported in the literature. Although further evidence is needed to confirm the usefulness and safety of balloon angioplasty for intracranial GCA, this case report provides valuable information about the endovascular therapy for GCA.

Filamin A Variant as a Possible Second-Hit Gene Promoting Moyamoya Disease-like Vascular Formation Associated With RNF213 p.R4810K Variant.

Background and Objective: The objective of this case report was to identify a second-hit gene that may promote Moyamoya disease (MMD)-like vascular formation in an individual having the RNF213 p.R4810K variant. Methods: We performed magnetic resonance imaging and genetic analyses of RNF213 and FLNA in a 21-year-old woman, who showed Ehlers-Danlos-like symptoms and developed a first-ever unprovoked seizure, and of her healthy parents. Results: We identified bilateral periventricular nodular heterotopia (PNH) as the cause of seizures and MMD-like vascular formation in the patient. The patient had the RNF213 p.R4810K variant. Exome analysis identified c.4868delG in the X-linked FLNA gene encoding filamin A p.G1623V fs*41, which could explain PNH and Ehlers-Danlos-like symptoms. Her mother had the same FLNA variant and had asymptomatic bilateral PNH, whereas her father had the RNF213 variant and had normal cerebrovascular structure. Discussion: The family study suggested that the FLNA variant promoted MMD-like vascular formation in a patient having the RNF213 variant, while the RNF213 variant amplified the phenotypic changes elicited by the FLNA abnormality. Collectively, we identified a gene abnormality in filamin A, a target of RNF213-mediated proteasomal degradation, that may promote MMD-like vascular formation as a possible second-hit gene in individuals having the RNF213 p.R4810K variant.

Subacute Methotrexate Encephalopathy Mimicking Ischemic Stroke With Dynamic Changes on Magnetic Resonance Imaging.

We report a 35-year-old woman who suddenly developed left hemiparesis and dysarthria at 13days after treatment with intrathecal and intravenous methotrexate for intravascular large B cell lymphoma with possible central nervous system infiltration. Seven hours after onset, she developed further right hemiparesis and aphasia. However, the majority of neurologic symptoms disappeared spontaneously and completely by 34hours. We also recorded the dynamic progression and regression of abnormal signals in the bilateral corona radiata on diffusion-weighted imaging, in parallel with neurologic symptoms. The rapid reversal of MR abnormalities and neurologic symptoms allowed us to diagnose methotrexate encephalopathy, and exclude intravascular large B cell lymphoma recurrence and regular brain infarction. The case provides new data on the dynamic changes of abnormal signals on magnetic resonance imaging in methotrexate encephalopathy over a short recovery time.

Influence of Statin Pretreatment on Initial Neurological Severity and Short-Term Functional Outcome in Acute Ischemic Stroke Patients: The Fukuoka Stroke Registry.

BACKGROUND: Statins have neuroprotective effects against ischemic stroke. However, associations between pre-stroke statin treatment and initial stroke severity and between the treatment and functional outcome remain controversial. This study aimed at determining these associations in ischemic stroke patients. METHODS: Among patients registered in the Fukuoka Stroke Registry from June 2007 to October 2014, 3,848 patients with ischemic stroke within 24 h of onset, who had been functionally independent before onset, were enrolled in this study. Ischemic stroke was classified as cardioembolic or non-cardioembolic infarction. Primary and secondary study outcomes were mild neurological symptoms defined as a National Institutes of Health Stroke Scale score of ≤4 on admission and favorable functional outcome defined as a modified Rankin Scale score of ≤2 at discharge, respectively. Multivariable logistic regression models were used to quantify associations between pre-stroke statin treatment and study outcomes. RESULTS: Of all 3,848 participants, 697 (18.1%) were taking statins prior to the stroke. The frequency of mild neurological symptoms was significantly higher in patients with pre-stroke statin treatment (64.1%) than in those without the treatment (58.3%, p < 0.01). Multivariable analysis showed that pre-stroke statin treatment was significantly associated with mild neurological symptoms (OR 1.31; 95% CI 1.04-1.65; p < 0.01). Sensitivity analysis in patients with dyslipidemia (n = 1,998) also showed the same trend between pre-stroke statin treatment and mild neurological symptoms (multivariable-adjusted OR 1.26; 95% CI 0.99-1.62; p = 0.06). In contrast, the frequency of favorable functional outcome was not different between patients with (67.0%) and without (65.3%) the treatment (p = 0.40). Multivariable analysis also showed no significant association between pre-stroke statin treatment and favorable functional outcome (OR 1.21; 95% CI 0.91-1.60; p = 0.19). Continuation of statin treatment, however, was significantly associated with favorable functional outcome among patients with pre-stroke statin treatment (multivariable-adjusted OR 2.17; 95% CI 1.16-4.00; p = 0.02). CONCLUSIONS: Pre-stroke statin treatment in ischemic stroke patients was significantly associated with mild neurological symptoms within 24 h of onset. Pre-stroke statin treatment per se did not significantly influence the short-term functional outcome; however, continuation of statin treatment during the acute stage of stroke seems to relate with favorable functional outcome for patients with pre-stroke statin treatment.

Cerebral vascular dysfunction during hypercholesterolemia.

BACKGROUND AND PURPOSE: Studies of peripheral arteries in hypercholesterolemic animals suggest that increased generation of superoxide contributes to endothelial dysfunction, especially in the presence of atherosclerotic lesions. We tested the hypothesis that vasomotor function is impaired in cerebral arterioles during hypercholesterolemia through a mechanism that involves oxidative stress. METHODS: Apolipoprotein E-deficient (apoE(-/-)) mice were fed a normal or a high-fat diet for >6 months. ApoE(+/-) mice fed a normal diet were used as normocholesterolemic controls. Responses of cerebral arterioles were examined in open cranial windows in vivo in anesthetized mice. RESULTS: In apoE(-/-) mice, intimal area was increased only in the proximal aorta on the normal diet and also markedly increased in the distal aorta on the high-fat diet. There were no increases in intimal area in the aortas of control mice or in the cerebral arterioles in any group. The dilator response of cerebral arterioles to ACh (10 micromol/L) in control mice (26+/-4% increase in diameter) was reduced in apoE(-/-) mice on either the normal (13+/-2%) or the high-fat (13+/-3%) diet (P<0.05 vs control). NADPH (10 micromol/L), a substrate for NADPH oxidase, produced dilator responses in control mice (8+/-4%) that were significantly increased in apoE(-/-) mice on the high-fat diet (16+/-2%, P<0.05 vs control). Tempol, a superoxide scavenger, and apocynin, an inhibitor of NADPH oxidase, significantly increased vasodilator responses to ACh and decreased vasodilation to NADPH in apoE(-/-) mice on the high-fat diet. Nitroprusside produced a similar dilatation in the cerebral arterioles of all groups. CONCLUSIONS: Hypercholesterolemia is associated with oxidative stress and endothelial dysfunction in cerebral arterioles, despite the absence of atherosclerotic lesions.

Modulation of dilator responses of cerebral arterioles by extracellular superoxide dismutase.

BACKGROUND AND PURPOSE: Extracellular superoxide dismutase (ECSOD) is highly expressed in the wall of blood vessels and plays an important role in modulation of vascular function in extracranial arteries. Expression of ECSOD appears to affect cerebral vascular responses during disease states. Effects of ECSOD on dilator function in cerebral arterioles, however, have not been fully elucidated. In the present study, we examined effects of ECSOD deficiency on cerebrovascular reactivity under control conditions and during oxidative stress. METHODS: Dilator responses of cerebral arterioles were examined in cranial windows in vivo in anesthetized ECSOD-deficient (-/-) and wild-type (+/+) mice under normal conditions and during oxidative stress induced by angiotensin II. RESULTS: Total SOD activity in the aorta in ECSOD-/- mice (176+/-24 [mean+/-SEM] U/mg) was approximately 30% lower than in ECSOD+/+ mice (270+/-38, P=0.051). Dilator responses to acetylcholine (10 micromol/L) in cerebral arterioles were similar under control conditions in ECSOD+/+ (34+/-5% changes in diameter) and -/- mice (32+/-4%). Angiotensin II (500 nmol/L for 30 minutes) tended to reduce responses to acetylcholine in ECSOD+/+ mice (not significant) and significantly impaired responses in ECSOD-/- mice (42% reduction, P<0.05). Tempol (1 mmol/L), a scavenger of superoxide, restored the impaired dilator responses in ECSOD-/- mice. Responses to nitroprusside in cerebral arterioles were similar in ECSOD+/+ and -/- mice and were not affected by angiotensin II nor by tempol. CONCLUSIONS: ECSOD deficiency has little effect on cerebrovascular reactivity in control conditions but plays an important role in the regulation of vascular tone during oxidative stress produced by angiotensin II.

Impairment of dilator responses of cerebral arterioles during diabetes mellitus: role of inducible NO synthase.

BACKGROUND AND PURPOSE: During diabetes, expression of inducible nitric oxide synthase (iNOS) plays an important role in the development of endothelial dysfunction in extracranial blood vessels. Progression of vascular dysfunction after the onset of diabetes differs among vascular beds. In this study, the effects of hyperglycemia/diabetes on vasomotor function were examined in cerebral arterioles at 2 different times in control and iNOS-deficient mice and compared with the effects on carotid arteries. METHODS: Streptozotocin (150 mg/kg IP) was given to induce diabetes. The diameter of cerebral arterioles was measured through a cranial window in diabetic and nondiabetic mice in vivo. Vasomotor function of the carotid artery was examined in vitro. RESULTS: In diabetic mice, responses of the cerebral arterioles to acetylcholine (1 mumol/L) were normal after 3 weeks of diabetes but were significantly impaired after 5 to 6 weeks of diabetes (4+/-1% [mean+/-SEM] increase in diameter) compared with control mice (14+/-1; P=0.0002). Responses to sodium nitroprusside were similar in diabetic and nondiabetic mice at both time points. In contrast, the vasomotor function of the carotid artery was not affected after 5 to 6 weeks of diabetes. In diabetic iNOS-deficient mice, cerebral arteriolar vasomotor function was not impaired, even after 4 months of diabetes. CONCLUSIONS: During diabetes, endothelial dysfunction of cerebral arterioles requires expression of iNOS and develops earlier than in carotid arteries.

[A case of cardioembolic brain infarction in arrhythmogenic right ventricular dysplasia].

We report a 45-year-old woman with arrhythmogenic right ventricular dysplasia (ARVD). Because of congestive heart failure and atrial fibrillation, she underwent tricuspid valvular replacement and warfarin was prescribed. She suddenly had dysarthria, left hemiparesis and left hemispatial neglect. After brain CT examination, and cerebral angiography, she was diagnosed as cardiogenic brain embolism and infusion of low molecular heparin was started. On day 25, she suddenly had ventricular tachycardia and died in spite of treatment for arrhythmia. This is the first report of the case of cardiogenic brain embolism following ARVD. In this type of case, we must take care of arrhythmia besides the management of atrial fibrillation and brain infarction.

Chronic administration of a tyrosine kinase inhibitor restores functional and morphological changes of the basilar artery during chronic hypertension.

OBJECTIVE: Activation of tyrosine kinase appears to play an important role in pathogenesis of cardiovascular disease during chronic hypertension. In the present study, we tested the hypothesis that long-term treatment with an inhibitor of tyrosine kinase would have beneficial effects on hypertension-induced morphological and functional changes of the cerebral artery. METHODS: Male spontaneously hypertensive rats (SHR; 4 months old) were fed normal rat chow, or that containing an inhibitor of tyrosine kinase, genistein (1 mg/kg chow). Normotensive Wistar-Kyoto (WKY) rats were also fed either of the chows. After feeding the rats for 2 months, we measured wall thickness, diameter of the basilar artery and its dilator responses to acetylcholine (ACh); Y-26763, an opener of ATP-sensitive potassium channels; and Y-27632, an inhibitor of Rho-associated kinase. RESULTS: Treatment with genistein did not cause significant changes in physiological variables, including mean arterial pressure in either strain. In control SHR, the wall thickness of the basilar artery was greater than that of WKY rats. Genistein treatment reduced the wall thickness significantly in SHR. Vasodilator responses induced by ACh and Y-26763 were markedly attenuated in SHR compared to WKY rats, and treatment of SHR with genistein significantly improved the vasodilatation. Dilatation of the artery in response to Y-27632 was enhanced in SHR compared to WKY rats and treatment of SHR with genistein did not affect the enhanced vasodilator responses to Y-27632. CONCLUSIONS: Chronic treatment with genistein may be a novel approach to prevent cerebrovascular disorders.

Long-term effects of benidipine on cerebral vasoreactivity in hypertensive rats.

We tested the hypothesis that long-term application of a Ca2+ channel blocker would ameliorate the functional and morphological deterioration of the cerebral arteries during hypertension. Male spontaneously hypertensive rats (SHR) were fed a standard rat chow, containing a low (3 mg/kg/day) or high dose (6 mg/kg/day) of benidipine, a Ca2+ channel blocker, for 2 months. Using a cranial window, we examined responses of the basilar artery to acetylcholine, sodium nitroprusside, (-)-(3S,4R)-4-(N-acetyl-N-hydroxyamino)-6-cyano-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-3-ol (Y-26763; an opener of ATP-sensitive K+ channels), and (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide (Y-27632; an inhibitor of Rho-associated kinase). Mean arterial pressure of the control group was 193+/-5 mm Hg (mean+/-S.E.M.), while that of the low-dose benidipine group was 183+/-5 mm Hg and that of the high-dose group was 159+/-4 mm Hg. Dilator responses of the basilar artery to acetylcholine and Y-26763 were impaired in SHR compared with those of normotensive Wistar-Kyoto (WKY) rats and treatment with benidipine enhanced the vasodilator responses to acetylcholine and Y-26763 in SHR. Y-27632-induced dilatation of the basilar artery was enhanced in SHR compared to that in WKY rats and the vasodilatation was reduced by benidipine in SHR. Sodium nitroprusside caused similar dilatation of the basilar artery, in both WKY rats and the SHR control group, and benidipine did not affect nitroprusside-induced dilatation of the artery in SHR. The wall of the basilar artery was significantly thicker in SHR than in WKY rats and benidipine treatment reduced the wall thickness of the artery in SHR. These findings suggest that chronic treatment with a Ca2+ channel blocker may enhance the dilator capacity and reduce contractility of the basilar artery during hypertension. Benidipine may also ameliorate the morphological changes of the basilar artery in hypertension.