Therapeutic-induced hypertension in patients with noncardioembolic acute stroke.

OBJECTIVE: To evaluate the safety and efficacy of induced hypertension in patients with acute ischemic stroke. METHODS: In this multicenter randomized clinical trial, patients with acute noncardioembolic ischemic stroke within 24 hours of onset who were ineligible for revascularization therapy and those with progressive stroke during hospitalization were randomly assigned (1:1) to the control and intervention groups. In the intervention group, phenylephrine was administered intravenously to increase systolic blood pressure (SBP) up to 200 mm Hg. The primary efficacy endpoint was early neurologic improvement (reduction in NIH Stroke Scale [NIHSS] score of ≥2 points during the first 7 days). The secondary efficacy endpoint was a modified Rankin Scale score of 0 to 2 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage/edema, myocardial infarction, and death. RESULTS: In the modified intention-to-treat analyses, 76 and 77 patients were included in the intervention and control groups, respectively. After adjustment for age and initial stroke severity, induced hypertension increased the occurrence of the primary (odds ratio 2.49, 95% confidence interval [CI] 1.25-4.96, p = 0.010) and secondary (odds ratio 2.97, 95% CI 1.32-6.68, p = 0.009) efficacy endpoints. Sixty-seven (88.2%) patients of the intervention group exhibited improvements in NIHSS scores of ≥2 points during induced hypertension (mean SBP 179·7 ± 19.1 mm Hg). Safety outcomes did not significantly differ between groups. CONCLUSION: Among patients with noncardioembolic stroke who were ineligible for revascularization therapy and those with progressive stroke, phenylephrine-induced hypertension was safe and resulted in early neurologic improvement and long-term functional independence. CLINICALTRIALSGOV IDENTIFIER: NCT01600235. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with acute ischemic stroke, therapeutic-induced hypertension increases the probability of early neurologic improvement.

Genetic Polymorphisms rs699947, rs1570360, and rs3025039 on the VEGF Gene Are Correlated with Extracranial Internal Carotid Artery Stenosis and Ischemic Stroke.

Extracranial internal carotid artery (ECICA) stenosis is a modifiable risk factor of ischemic stroke. VEGF plays a crucial role in the maintenance of endothelial integrity and physiological function. This study was designed to assess the correlations of VEGF polymorphisms with ECICA stenosis in ischemic stroke and to explore the relationships between these polymorphisms and different biochemical parameters. This study included a total of 650 ischemic stroke patients, 232 with ECICA stenosis while 418 had no ECICA stenosis as assessed by magnetic resonance angiography. Three SNPs in the VEGF gene, rs699947, rs1570360, and rs3025039, were assessed by real-time PCR coupled with melting curve analysis. Serum samples were analyzed for biochemical parameters in an automated clinical chemistry analyzer in the Laboratory Medicine Department. The CA and CA+AA (A allele bearing) genotype frequencies of the rs699947 polymorphism (AOR=1.46 and 1.47, respectively) and the GA genotype frequency of the rs1570360 polymorphism (AOR=7.33) showed a significant association with ECICA stenosis. However, the haplotype frequencies of C-A-A, T-A-C, and T-A-A (rs302503-rs1570360-rs699947) were significantly different between patients who experienced stroke with and stroke without ECICA stenosis. We found that the total homocysteine (tHcy) levels of stroke patients with ECICA stenosis with rs1570360 and rs699947 SNPs were significantly different compared to the wild-type reference genotype. In conclusion, VEGF rs699947 and rs3025039 polymorphisms were associated with increased risk of stroke, while rs1570360 and rs699947 were associated with stroke and ECICA stenosis.

Basilar artery angulation in association with aging and pontine lacunar infarction: a multicenter observational study.

AIM: Deep pontine lacunar infarction (DPLI) not involving the basal pial surface of the medial part of the pons, is known to be a small vessel disease in the territory of the basilar artery (BA). In the present study, we examined whether morphological features of the BA differ in individuals with an advanced age and may be associated with DPLI. METHODS: This study included 338 healthy subjects and 78 patients with DPLI treated at the stroke centers of three university hospitals in Korea. Time-Of-Flight magnetic resonance angiographic images were transported to a central lab and analyzed blind to obtain the clinical data. For the quantitative analysis, the BA was projected two-dimensionally in the anteroposterior and lateral views and perceived as triangles of the vertebrobasilar junction, angulation point and BA division. The angles and triangular areas were summated into angulation indexes and used to quantify the degree of BA tortuosity. RESULTS: The BA showed a more acute angle at the angulation point in the elderly patients than in the healthy subjects. Compared to the healthy subjects, the DPLI patients exhibited significantly larger angles at the vertebrobasilar junction, in addition to the acute angles noted at the angulation point. A unit increase in the BA angle indexes at the vertebrobasilar junction and angulation points for DPLI was found to have an odds ratio of 1.15 (95% confidence interval, 1.05-1.26) and 0.95 (95% CI, 0.91-0.99), respectively, even after adjusting for potential confounders. CONCLUSIONS: The angulation point of the BA becomes more acute in elderly individuals. In this study, the vertebrobasilar junction showed a larger angle in the patients with DPLI than in the healthy controls.

Establishment of government-initiated comprehensive stroke centers for acute ischemic stroke management in South Korea.

BACKGROUND AND PURPOSE: In 2008, the Ministry of Health and Welfare of South Korea initiated the Regional Comprehensive Stroke Center (CSC) program to decrease the incidence and mortality of stroke nationwide. We evaluated the performance of acute ischemic stroke management after the Regional CSC program was introduced. METHODS: The Ministry of Health and Welfare established 9 Regional CSCs in different provinces from 2008 to 2010. All Regional CSCs have been able to execute the critical processes independently for stroke management since 2011. The Ministry of Health and Welfare was responsible for program development and financial support, the Regional CSC for program execution, and the Korea Centers for Disease Control and Prevention for auditing the execution. We analyzed prospectively collected data on the required indices from 2011 and repeated the analysis the following year for comparison. RESULTS: After the Regional CSCs were established, the first brain image was taken within 1 hour from arrival at the emergency room for all patients with stroke; the length of hospital stay decreased from 14 to 12 days; for the rapid execution of thrombolysis, the first brain image was taken within 12 minutes; intravenous and intra-arterial thrombolysis were started within 40 and 110 minutes, respectively, after emergency room arrival; and the hospital stay of thrombolytic patients decreased from 19 to 15 days. CONCLUSIONS: The Regional CSC program has improved the performance of acute stroke management in South Korea and can be used as a model for rapidly improving stroke management.

To do or not to do; dilemma of intra-arterial revascularization in acute ischemic stroke.

BACKGROUND: There has still been lack of evidence for definite imaging criteria of intra-arterial revascularization (IAR). Therefore, IAR selection is left largely to individual clinicians. In this study, we sought to investigate the overall agreement of IAR selection among different stroke clinicians and factors associated with good agreement of IAR selection. METHODS: From the prospectively registered data base of a tertiary hospital, we identified consecutive patients with acute ischemic stroke. IAR selection based on the provided magnetic resonance imaging (MRI) results and clinical information were independently performed by 5 independent stroke physicians currently working at 4 different university hospitals. MRI results were also reviewed by 2 independent experienced neurologists blinded to clinical data and physicians' IAR selection. The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) was calculated on initial DWI and MTT. We arbitrarily used ASPECTS differences between DWI and MTT (D-M ASPECTS) to quantitatively evaluate mismatch. RESULTS: The overall interobserver agreement of IAR selection was fair (kappa = 0.398). In patients with DWI-ASPECTS >6, interobserver agreement was moderate to substantial (0.398-0.620). In patients with D-M ASPECTS >4, interobserver agreement was moderate to almost perfect (0.532-1.000). Patients with higher DWI or D-M ASPECTS had better agreement of IAR selection. CONCLUSION: Our study showed that DWI-ASPSECTS >6 and D-M ASPECTS >4 had moderate to substantial agreement of IAR selection among different stroke physicians. However, there is still poor agreement as to whether IAR should not be performed in patients with lower DWI and D-M ASPECTS.

Ectopic choroid plexus found in fetal sections: a case report with literature consideration.

We incidentally found an ectopic choroid plexus (CP) attached to the posterior side of the cervicothoracic spinal cord (C4-T6) in a 16-week aborted fetus. The cytoarchitecture of the cord and segmental nerves showed normal development. The fourth ventricle did not contain the usual CP but a red blood cell cluster due to hemorrhage, although the cause, whether spontaneous or traumatic, was unknown. The ectopic CP was associated with thick neuroepithelium that was strongly positive for glial fibrillary acidic protein, vimentin, nestin, and proliferating cell nuclear antigen, but did not contain any CD34-positive vessels. Thus, the ectopic neuroepithelium seemed not to carry growth factor for vascular development. On the inferior side of the ectopic CP, the lower thoracic cord was wavy, folded, and packed in a limited space as a folding fan. Despite the strange gross appearance, however, we found no abnormality in the dorsal root ganglion, the spinal nerve root, or the cytoarchitecture of the lower thoracic cord. Therefore, the abnormality in the lower thoracic cord seemed to be secondarily induced by trophic factor(s) from the ectopic CP and/or the associated neuroepithelium. This may be the first report on an ectopic CP associated with ectopic neuroepithelium.

Association of aortic knob calcification with intracranial stenosis in ischemic stroke patients.

BACKGROUND AND PURPOSE: Aortic knob calcification (AC) is associated with increased risks of cardiovascular and cerebrovascular events. We evaluated the clinical importance of AC in ischemic stroke patients with intracranial (IC) stenosis using simple, non-invasive and routine chest radiography. METHODS: The presence of AC was assessed in a chest posteroanterior view in 307 acute ischemic stroke patients admitted from May 2009 to April 2010, and who underwent magnetic resonance angiography or distal subtraction angiography. The association of AC with IC stenosis was analyzed. RESULTS: Patient age (68.3±8.7 vs. 65.9±8.27 years, P=0.04), and the prevalence of IC stenosis (70.7 vs. 41.3%, P<0.01) were higher in patients with AC than in patients without calcification. After adjusting for age, gender and vascular risk factors, logistic regression analysis showed that AC (Odds ratio, 3.54; 95% confidence interval, 1.90 to 6.61, P<0.01) and age (Odds ratio, 1.79; 95% confidence interval, 1.01 to 3.19; P=0.04) were independent factors affecting IC stenosis. CONCLUSIONS: AC appears to be a reliable predictor for IC stenosis, an important mechanism of ischemic stroke.

Early fetal development of the human vertebral artery especially at and above the occipitovertebral junction.

Little is known about the chronological changes that occur in the topographical anatomy of the fetal vertebral artery (VA), especially at and above the occipitovertebral junction. We histologically examined paraffin-embedded horizontal, sagittal and frontal sections of the heads of 25 human embryos and fetuses of crown-rump length 20-110 mm, corresponding to 6-15 weeks of gestation. At 6 weeks, the VA ran anterosuperiorly through a large intracranial subdural space filled with loose mesenchymal tissue. This intracranial course was distant from the brain stem, suggesting that the developing brain did not "guide" the VA. Before 8-9 weeks, the VA appeared to take an almost straight upward course at the occipitovertebral junction. Later, however, the atlanto-occipital joint growing along the mediolateral axis caused the VA to curve at the junction area. In specimens before 10 weeks, the terminal of the VA, or the origin of the basilar artery, was on the anterior side of the inferior olive and near the jugular foramen. The fetal posterior inferior cerebellar artery originated at the same caudal site distant from the primitive cerebellum. Later, the terminal or origin moved rostrally to the level of the pons. These findings indicate that the basic branching pattern of the VA-basilar artery is independent of the developing brain, whereas the arterial courses are secondarily "corrected" by the growing brain and atlanto-occipital joint.

Orgasmic headache treated with nimodipine.

INTRODUCTION: Orgasmic headache (OH) is a sudden and severe headache that occurs at the time of or shortly after an orgasm. AIM.: We present the case of typical primary headache associated with sexual activity, especially during an orgasmic period. METHODS: A 34-year-old man complained of sudden and severe headache during sexual activity, or orgasmic period, for 2 months. The headache developed abruptly with an orgasm and then decreased shortly over a period of 4 ≈ 8 hours. RESULTS: Magnetic resonance angiography revealed severe spasm of the M1 segment of both the middle cerebral arteries. He was treated with oral nimodipine (30 mg every 8 hours), which alleviated the headache and prevented its recurrence. CONCLUSIONS: We postulated a pathophysiological relationship between OH and migraine, especially with respect to vasoconstriction, and believe that in such cases, nimodipine may be an effective therapy.

Sulcal effacement on fluid attenuation inversion recovery magnetic resonance imaging in hyperacute stroke: association with collateral flow and clinical outcomes.

BACKGROUND AND PURPOSE: The clinical significance of sulcal effacement has been widely investigated in CT studies, but the results are controversial. In this study, we evaluated the presence of perisylvian sulcal effacement (PSE) on fluid attenuation inversion recovery MRI and hypothesized that PSE may be related to collateral flow status together with hyperintense vessels on fluid attenuation inversion recovery in hyperacute stroke. In addition, we investigated whether an association between PSE and clinical outcome could be found in these patients. METHODS: Consecutive patients with acute middle cerebral artery infarcts within 6 hours of symptom onset were included. All patients had internal carotid artery or middle cerebral artery occlusion and underwent MRI including FLAIR. The presence of PSE and hyperintense vessels on fluid attenuation inversion recovery and the collateral status and occurrence of early recanalization (ER) on conventional angiography were evaluated. RESULTS: Of 139 patients, 79 (56.8%) had PSE. Multivariate testing revealed PSE was independently associated with collateral status. The association between hyperintense vessels and collaterals was different depending on PSE. Compared to PSE-positive and ER-negative patients, PSE-negative and ER-negative patients (odds ratio, 4.11; 95% confidence interval, 1.12-15.17) and PSE-negative and ER-positive patients (odds ratio, 34.62; 95% confidence interval, 5.75-208.60), but not PSE-positive and ER-positive patients, were more likely to experience favorable clinical outcomes (modified Rankin Scale score ≤ 2 at 3 months). CONCLUSIONS: PSE is independently associated with collateral status in patients with acute middle cerebral artery stroke. Moreover, PSE in conjunction with recanalization status can predict clinical outcomes in these patients.

The anatomy of fetal peripheral lymphatic vessels in the head-and-neck region: an immunohistochemical study.

Using D2-40 immunohistochemistry, we assessed the distribution of peripheral lymphatic vessels (LVs) in the head-and-neck region of four midterm fetuses without nuchal edema, two of 10 weeks and two of 15 weeks' gestation. We observed abundant LVs in the subcutaneous layer, especially in and along the facial muscles. In the occipital region, only a few LVs were identified perforating the back muscles. The parotid and thyroid glands were surrounded by LVs, but the sublingual and submandibular glands were not. The numbers of submucosal LVs increased from 10 to 15 weeks' gestation in all of the nasal, oral, pharyngeal, and laryngeal cavities, but not in the palate. The laryngeal submucosa had an extremely high density of LVs. In contrast, we found few LVs along bone and cartilage except for those of the mandible as well as along the pharyngotympanic tube, middle ear, tooth germ, and the cranial nerves and ganglia. Some of these results suggested that cerebrospinal fluid outflow to the head LVs commences after 15 weeks' gestation. The subcutaneous LVs of the head appear to grow from the neck side, whereas initial submucosal LVs likely develop in situ because no communication was evident with other sites during early developmental stages. In addition, CD68-positive macrophages did not accompany the developing LVs.