Elevated glucose level adversely affects infarct volume growth and neurological deterioration in non-diabetic stroke patients, but not diabetic stroke patients.

BACKGROUND AND PURPOSE: Hyperglycemia is recognized as a common occurrence associated with a high risk of poor outcome in ischaemic stroke patients. However, little is known about the association between elevated glucose level, growth of infarct volume and neurological deterioration in ischaemic stroke patients without diabetes. The present study aimed to clarify this issue in acute ischaemic stroke patients with arterial occlusion. METHODS: We studied 375 acute ischaemic stroke patients with arterial occlusion within 24 h of onset. Diabetes was diagnosed in patients with a known history of diabetes or HbA1c value ≥ 6.5%. Infarct volume was measured on admission and at follow-up within 48 h using diffusion-weighted imaging. Neurological deterioration was defined as an increase of ≥ 4 points in National Institutes of Health Stroke Scale score within 7 days of stroke onset. We examined the relationship between glucose level on admission, infarct volume growth and neurological deterioration in three categories (all patients, non-diabetes and diabetes) using multivariate modeling. RESULTS: Diabetes was present in 104 patients (27.7%). Multivariate regression analysis showed that elevated glucose level was independently associated with infarct volume growth in all patients (P = 0.034) and non-diabetes (P = 0.002), but not in diabetes (P = 0.871). Moreover, elevated glucose level was independently associated with neurological deterioration in all patients [odds ratio (OR), 1.010; 95% confidence interval (CI), 1.004-1.017; P = 0.002] and non-diabetes (OR, 1.014; 95% CI, 1.002-1.026; P = 0.022), but not diabetes (OR, 1.006; 95% CI, 0.998-1.014; P = 0.151). CONCLUSIONS: Glucose level appears to influence infarct volume growth and neurological deterioration, particularly in non-diabetic patients with ischaemic stroke.

Dysarthria plus dysphagia is associated with severe sleep-disordered breathing in patients with acute intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Sleep-disordered breathing (SDB) is a risk factor for stroke. The frequency of SDB in Japanese patients with acute intracerebral hemorrhage (ICH) was investigated, as well as factors associated with SDB severity. METHODS: Between April 2010 and April 2013, patients with ICH within 24 h of onset were prospectively enrolled to participate in a sleep study within 7 days of admission. SDB was defined as a respiratory disturbance index (RDI: apnea or hypopnea events per hour) of ≥ 5. Patients were assigned to groups based on RDI values of ≥ 30 (severe SDB) and <30 (absent or not severe SDB). The frequency of SDB and factors associated with its severity were investigated using multivariate logistic regression analysis. RESULTS: Of 97 patients (55 males; mean age 68.1 years) enrolled in the study, 91 (94%) had SDB. Severe SDB was evident in 29 (30%) patients. Compared with the RDI< 30 group, the RDI ≥ 30 group had a higher frequency of dysarthria plus dysphagia (76% vs. 47%, P = 0.008), larger waist circumference [86 (84-92) vs. 84 (78-88) cm, P = 0.019] and a greater body mass index [23.8 (21.1-26.8) vs. 21.5 (19.4-25.0) kg/m(2), P = 0.046]. Multivariate logistic regression analysis showed that dysarthria plus dysphagia was independently associated with severe SDB (odds ratio 3.4; 95% confidence interval 1.250-9.252, P = 0.017). CONCLUSION: Most Japanese patients with acute ICH had SDB, and dysarthria plus dysphagia was associated with severe SDB.

Atrial fibrillation is associated with severe sleep-disordered breathing in patients with ischaemic stroke and transient ischaemic attack.

BACKGROUND AND PURPOSE: Sleep-disordered breathing (SDB) is a risk factor for cerebrovascular disease. We investigated the frequency of SDB in Japanese patients with acute ischaemic stroke and transient ischaemic attack (TIA), as well as factors associated with SDB severity. METHODS: Between April 2010 and March 2011, we prospectively enrolled patients with ischaemic stroke and TIA within 24 h of onset to participate in a sleep study within 7 days of admission. We defined SDB as a respiratory disturbance index (RDI) (number of apnoeas or hypopnoeas per hour) of ≥ 5. Patients were assigned to groups based on RDI values of ≥ 30 (severe) and <30 (absent or not severe). The frequency of SDB and factors associated with severity were investigated using multivariate regression analysis. RESULTS: We enrolled 150 patients amongst whom 126 (84%) had SDB. The frequencies of SDB were 21 (75%) patients with TIA, 105 (86%) with ischaemic stroke, 8/10 (80%) with large artery atherosclerosis, 14/14 (100%) with small vessel occlusion, 37/41 (90%) with cardioembolism and 46/57 (81%) with other causes of stroke/undetermined. Severe SDB was evident in 44 (29%) patients. The frequency of males (75% vs. 56%, P = 0.027), atrial fibrillation (AF) (39% vs. 23%, P = 0.045), higher body mass index (23.8 ± 3.8 vs. 22.3 ± 3.8, P = 0.043) and a larger neck circumference (37.8 ± 4.3 vs. 35.8 ± 4.2, P = 0.012) was significantly higher in the group with severe SDB. Multivariate regression analysis found that AF (OR 2.4; 95% CI 1.079-5.836, P = 0.0359) was independently associated with severe SDB. CONCLUSION: Most Japanese patients with acute ischaemic stroke and TIA had SDB, and AF was associated with SDB.

Admission hyperglycemia causes infarct volume expansion in patients with ICA or MCA occlusion: association of collateral grade on conventional angiography.

BACKGROUND AND PURPOSE: Hyperglycemia (HG) is associated with infarct volume expansion in acute ischaemic stroke patients. However, collateral circulation can sustain the ischaemic penumbra and limit the growth of infarct volume. The aim of this study was to determine whether the association between HG and infarct volume expansion is dependent on collateral circulation. METHODS: We performed a retrospective analysis of 93 acute ischaemic stroke patients with internal carotid artery or middle cerebral artery occlusion within 24 h of onset were retrospectively studied. HG was diagnosed in patients with an admitting blood glucose value ≥140 mg/dl. Angiographic collateral grade 0-1 was designated as poor collateral circulation and grade 2-4 as good collateral circulation. Infarct volume was measured at admission and at again within 7 days using diffusion-weighted magnetic resonance images. RESULTS: Among 34 patients with poor collateral grade, the change in infarct volume was significantly greater in the HG group than in the non-HG group (106.0 ml vs. 22.7 ml, P = 0.002). Among the 59 patients with good collateral circulation, the change in infarct volume was greater in the HG group than in the non-HG group (53.3 ml vs. 10.9 ml, P = 0.047). Multiple regression analysis indicated that admission HG (P = 0.004), baseline National Institutes of Health Stroke Scale score (P = 0.018), and poor collateral circulation (P = 0.040) were independently associated with infarct volume expansion. CONCLUSIONS: Infarct volume expansion was greater in individuals with HG on admission regardless of collateral circulation status.

Plasma brain natriuretic peptide predicts death during hospitalization in acute ischaemic stroke and transient ischaemic attack patients with atrial fibrillation.

BACKGROUND AND PURPOSE: atrial fibrillation (AF) is the most powerful predictor of early death in patients with acute ischaemic stroke. We investigated whether the plasma brain natriuretic peptide (BNP) level on admission can serve as a biological marker of in-hospital death in acute ischaemic stroke and transient ischaemic attack (TIA) patients with AF. METHODS: we prospectively enrolled ischaemic stroke and TIA patients with AF within 24 h of onset and measured plasma BNP on admission. Patients were divided into two groups: the deceased group, who died during hospitalization, and the survival group. The factors associated with in-hospital death were investigated by multivariate logistic regression analysis. RESULTS: a total of 221 patients with AF were enrolled. Death occurred in 24 (10.9%) patients. The mean ± SD of the plasma BNP level of the deceased group was significantly higher than that of the survival group (714.1 ± 716.3 vs. 320.0 ± 380.7 pg/ml, P < 0.0001). The optimal cutoff level, sensitivity, and specificity of BNP levels to distinguish the deceased group from the survival group were 320 pg/ml, 79.2, and 69.0%, respectively. Multivariate logistic regression analysis demonstrated that age per 10 years increase (OR, 3.56; 95% CI, 1.728-7.346, P = 0.0006), internal carotid artery occlusion (OR, 10.20; 95% CI, 2.525-41.177, P = 0.0011), NIHSS score of >17 (OR, 4.68; 95% CI, 1.137-19.286, P = 0.0325), and plasma BNP level of > 320 pg/ml (OR, 4.74; 95% CI, 1.260-17.800, P = 0.0213) were independent factors associated with in-hospital death. CONCLUSION: the plasma BNP level on admission can predict in-hospital death in acute ischaemic stroke and TIA patients with AF.

Brain natriuretic peptide as a predictor of delayed atrial fibrillation after ischaemic stroke and transient ischaemic attack.

BACKGROUND AND PURPOSE: We investigated whether the brain natriuretic peptide (BNP) level can serve as a predictive biological marker of delayed atrial fibrillation (AF). METHODS: Two hundred and thirty seven consecutive patients admitted to our institution with acute ischaemic stroke or transient ischaemic attack (TIA) within 24 h of onset were enrolled. The patients were classified according to the presence or absence of AF upon admission [AF and sinus rhythm (SR) groups]. The SR group was subdivided based on the development of AF after admission (new- and non-AF groups). We compared the characteristics between the AF and SR groups, and between the new- and non-AF groups. The factors associated with new-AF were investigated by multivariate logistic regression analysis. RESULTS: Amongst the enrolled patients, 72 (30.4%) had AF upon admission (AF group), and 13 (5.5%) developed AF thereafter (new-AF group). The plasma BNP level was significantly higher in the AF, than in the SR group (401.7 vs. 92.1 pg/ml, P < 0.001). Moreover, the plasma BNP level was significantly higher in the new-, than in the non-AF group (184.7 vs. 84.1 pg/ml, P < 0.001). The optimal cutoff BNP level required to distinguish new-, from non-AF groups was 85.0 pg/ml, and the sensitivity and specificity was 83.3% and 76.2%, respectively. On multivariate logistic regression analysis, plasma BNP level >85.0 pg/ml (odds ratio, 7.20; 95% confidence interval, 1.71 to 30.43, P = 0.007) was an independent factor associated with new-AF. CONCLUSION: High plasma BNP level should be a strong predictor of delayed AF after ischaemic stroke or TIA.

Microembolic signals at 48 hours after stroke onset contribute to new ischaemia within a week.

BACKGROUND AND AIMS: We investigated whether new ischaemic lesions (NIL) on follow-up diffusion weighted magnetic resonance imaging (DWI) are associated with microembolic signals (MES) within 24 h or at 48 h after stroke onset. METHODS: Patients had acute ischaemic stroke and were studied within 24 h of onset. Transcranial Doppler ultrasonography (TCD) was prospectively examined twice, within 24 h and at 48 h after onset. DWI was conducted twice, on admission and on day 7. NIL were defined as the presence of hyperintense lesions undetected on initial DWI. RESULTS: 125 patients were consecutively enrolled from November 2004 to March 2006. TCD detected MES in 49% within 24 h and in 29% at 48 h after onset. In 27 patients with small vessel disease, MES were found in 8 (30%) patients within 24 h and in 5 (19%) patients at 48 h after stroke onset. In contrast, in 20 patients with large vessel disease, 11 (55%) patients within 24 h and 7 (35%) at 48 h had MES. Follow-up DWI detected NIL in 28 of 125 patients (22%) and NIL were significantly more frequent in MES positive patients (42%) than in MES negative patients at 48 h (15%; p = 0.002). MES at 48 h (OR 3.9; 95% CI 1.5 to 10; p = 0.005), atrial fibrillation (OR 3.6; 95% CI 1.3 to 11; p = 0.013) and arterial lesions (OR 4.3; 95% CI 1.5 to 12; p = 0.007) represented independent factors for NIL. CONCLUSION: The presence of MES at 48 h, atrial fibrillation and arterial lesions were associated with recurrence of cerebral ischaemia on DWI.

Right-to-left shunt and lacunar stroke in patients without hypertension and diabetes.

We analyzed the frequency of cardiac embolic sources in 62 patients with acute lacunar stroke vs 50 controls. In post hoc analysis, 11 patients with lacunar stroke having neither hypertension nor diabetes mellitus (non-HDM group) had a higher frequency of right-to-left shunt (RLS) (82%) than patients with risk factors for lacunar stroke. RLS was also independently associated with the non-HDM group. Thus, RLS may contribute to lacunar stroke in patients without risk factors for lacunar stroke.

[Sequential magnetic resonance imaging and neurophysiological studies in a patient with inferior spinal cord infarction].

A 66-year-old woman suddenly developed anterior spinal artery syndrome with complete flaccid paraplegia, superficial sensory disturbance caudally to the L5 dermatome level with preservation of deep sensation, incontinence, and absent deep tendon reflexes in both legs. An MRI of the whole spine and an analysis of the CSF 4 hours after onset were normal. The electrophysiological study showed an absence of F wave on the posterior tibial nerve stimulation on admission, while the peripheral nerve conduction velocities and amplitudes of upper and lower limbs were normal. T2-weighted MRI 4 days after onset demonstrated an area of high signal intensity in the gray and white matters of the epiconus and conus medullaris, and T1-weighted MRI showed the swelling. Three weeks later, F wave became evoked nd the high signal areas on axial T2-weighted MRI were localized in the bilateral anterior horns of the gray matter. T1-weighted MRIs after an administration of Gd-DTPA 3 and 7 weeks after onset demonstrated an enhancement of the ventral roots of the lumbar nerves and cauda equina, while the enhancements disappeared 8 months after onset. The patient was finally able to walk independently over 10 meter. An absent F wave was an only positive finding at the hyperacute (hours after onset) stage of the spinal cord infarction.

[A case of Bickerstaff's brainstem encephalitis during pregnancy].

Here we present a case of 23-year-old woman with Bickerstaff's brainstem encephalitis (BBE) during 13 weeks of pregnancy. After symptoms of the upper respiratory tract infection, she developed somnolence, marked disturbance of extraocular eye movements, cerebellar ataxia, hyperreflexia and spasticity of the lower limbs. An electroencephalogram revealed slow waves and brainstem auditory evoked potential disclosed prolongation of III-V interpeak intervals. Serum IgG anti-GQ1b antibody was detected. Plasma exchanges (PE) were performed four times. Although no patient with BBE during pregnancy has ever been reported, in the literatures the pregnant patients with Guillain-Barré syndrome had four sessions of plasmapheresis with safe. Neurological symptoms gradually improved after the PE. No serious adverse effects were noted. Although no definite therapy for BBE has been established, PE may be one of the selections even if the patients is pregnant.

Synthesis of Optically Active 1,4-Thiazane-3-carboxylic Acid via Optical Resolution by Preferential Crystallization of (RS)-2-Amino-3-[(2-chloroethyl)sulfanyl]propanoic Acid Hydrochloride.

Optically active 1,4-thiazane-3-carboxylic acid [TCA] was synthesized from cysteine via optical resolution by preferential crystallization. The intermediate (RS)-2-amino-3-[(2-chloroethyl)sulfanyl]propanoic acid hydrochlo-ride [(RS)-ACS•HCl] was found to exist as a conglomerate based on its melting point, solubility and IR spectrum. (RS)-ACS•HCl was optically resolved by preferential crystallization to yield (R)- and (S)-ACS•HCl. (R)- and (S)-ACS•HCl thus obtained were recrystallized from a mixture of hydrochloric acid and 2-propanol, taking account of the solubility of (RS)-ACS•HCl, efficiently yielding both enantiomers in optically pure forms. (R)- and (S)-TCA were then respectively synthesized by the cyclization of (R)- and (S)-ACS•HCl in ethanol in the presence of triethylamine.

Evaluation of chitin and chitosan on open would healing in dogs.

Analysis on the accelerating effects of open wound healing by chitin and chitosan were carried out in dogs. Two, square, full-thickness wounds of skin (2 x 2 cm2) were created on the each dog's both sides of dorsal midline at 0, 14, 21, and 24 days. In one dog, one wound (left side) was treated with chitin (chitin group) and the other wound (right side) was not treated (control group). In another dog, one wound (left side) was treated with chitosan (chitosan group) and the other wound (right side) was not treated (control group). At 28 days after initial wounding, each wound site including surrounding tissue was taken for macroscopic and histological observations. Reepithelialization tended to be greater in chitin and chitosan groups than in the control group. However, when the scores of reepithelialization and granulation tissue were evaluated statistically, there was no significant differences in three groups during experimental period. Number of inflammatory cells was greater statistically in level in the control group than those in chitin and chitosan groups at 28 days after wounding. Many rete ridges were observed in the control group but very few in the another groups.