Relation of glycated hemoglobin with carotid atherosclerosis in ischemic stroke patients: An observational study in Indian population

Context:

Glycated hemoglobin A₁c(HbA₁c) indicates long-term uncontrolled hyperglycemia in the body, which in diabetic patients leads to various vascular complications as a part of generalized atherosclerosis culminating ultimately into ischemic stroke.

Aims:

Study aims to show the association between marker of uncontrolled long-term hyperglycemia HbA₁c and marker of atherosclerosis (Carotid intima media thickness [CIMT] and carotid plaque) in ischemic stroke patients.

Subjects and Methods:

Carotid sonography using high resolution 7.5 MHz sonography technique was done in each patient to find the occurrence of increased CIMT and presence of plaque according to Mannheim CIMT Consensus (2004-2006). Levels of HbA₁c measured in blood in both diabetic and non-diabetic patients and a comparison made between them. Finally an association sought between HbA₁c levels with CIMT and plaque.

Results:

The average value of HbA₁c of this cohort was 7.51 ± 1.75% with higher values in diabetic patients (9.29 ± 1.73%). The patients with high CIMT (>0.8 mm) had higher values of HbA₁c then that of normal CIMT patients and this was nearly significantly (P = 0.06). However, HbA₁c levels of blood were significantly associated with stroke patients with presence of carotid arteries plaque (P = 0.008).

Conclusions:

Prediction of future risk and prevention strategies for ischemic stroke could be formulated by utilizing HbA₁c levels in both diabetic and non-diabetic population.     

N-terminal pro-brain natriuretic peptide levels and short term prognosis in acute ischemic stroke

Background:

Sparse published data are available regarding the prognostic importance of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with acute ischemic stroke.

Materials and Methods:

We prospectively studied 74 consecutive patients presenting with acute ischemic stroke within 24 hours of onset. All of them underwent laboratory and imaging evaluation and were treated as per guidelines. In all subjects, plasma NT-proBNP levels were measured at initial admission and again on day 7.

Results:

Their mean age was 54 ± 13.5years; there were 49 males; 18 (24%) patients died during the hospital stay. A statistically significant negative correlation between log NT-proBNP and Glasgow coma scale (GCS) score (P < 0.001); and a significant positive correlation between log NT-proBNP and National Institutes of Health Stroke Scale (NIHSS) score (P < 0.001) were observed. Baseline log NT-proBNP levels were higher among non-survivors compared with survivors (6.7 ± 0.47 vs. 5.37 ± 0.62; P = 0.06); day 7 log NT-proBNP levels were significantly higher in non-survivors compared with survivors (7.3 ± 0.26 vs. 4.5 ± 0.4; P = 0.000). In survivors, there was a statistically significant decline in log NT-proBNP levels from baseline to day 7 (5.3710 ± 0.620 vs. 4.5320 ± 0.451; P < 0.001). In contrast, among non-survivors, log NT-proBNP levels showed a statistically significant increase from baseline to day 7 (4.5322 ± 0.451 vs. 7.2992 ± 0.263; P < 0.001). On receiver operator characteristic curve (ROC) analysis, at a cut-off value of ≥ 6.0661, log NT-proBNP had a sensitivity and specificity of 98.2 and 88.9, respectively, in predicting death.

Conclusions:

Plasma log NT-pro-BNP level appears to be a useful biological marker for predicting in-hospital mortality inpatients presenting with acute ischemic stroke.     

The Response of Carotid Intima-Media Thickness to Medical Treatment Is Correlated with That of Intracranial Atherosclerosis

Background and Purpose

Intracranial atherosclerotic stenosis (ICAS) is considered as a major cause of stroke. The carotid intima-media thickness (CIMT), which accurately reflects the burden of generalized atherosclerosis, is also associated with stroke. The aim of this study was to determine the association between the CIMT and ICAS responses to medical treatment.

Methods

This study constituted part of the "Trial of cilostazol in symptomatic intracranial arterial stenosis"-2 that evaluated the ICAS response after randomized antiplatelet treatment. Magnetic resonance angiography and CIMT measurement were performed at baseline and after 7 months of treatment. CIMT was measured using semiautomated software, and was presented as maximum (CIMT-max) and average (CIMT-ave) values. The change in CIMT was compared relative to the ICAS response (i.e., progression, no-change, and regression). Ordinal logistic regression and analysis of covariance (ANCOVA) were used to analyze the association between the responses.

Results

Among the 101 enrolled patients, 85 underwent follow-up CIMT measurement. CIMT increased most in the ICAS progression group (CIMT-max: 0.09±0.23, CIMT-ave: 0.04±0.12), and to a lesser degree in the no-change group (CIMT-max: 0.02±0.16, CIMT-ave: 0.02±0.11), but decreased in patients with ICAS regression (CIMT-max: -0.04±0.11, CIMT-ave: -0.03±0.07; CIMT-max: p=0.010, CIMT-ave: p=0.015). Ordinal logistic regression analysis demonstrated that the change in CIMT-max was independently associated with the ICAS response (p=0.032). However, the ANCOVA revealed that the reverse was not true, in that the ICAS response was not independently associated with the change in CIMT after adjusting for confounding factors.

Conclusions

The ICAS response may be associated with the CIMT response to medical treatment.     

Ambulation following spinal cord injury and its correlates

Objectives:

To assess walking ability of spinal cord injury (SCI) patients and observe its correlation with functional and neurological outcomes.

Patients and Methods:

The present prospective, observational study was conducted in a tertiary research hospital in India with 66 patients (46 males) between January 2012 and December 2013. Mean age was 32.62 ± 11.85 years (range 16-65 years), mean duration of injury was 85.3 ± 97.6 days (range 14-365 days) and mean length of stay in the rehabilitation unit was 38.08 ± 21.66 days (range 14-97 days) in the study. Walking Index for spinal cord injury (WISCI II) was used to assess ambulation of the SCI patients. Functional recovery was assessed using Barthel Index (BI) and Spinal Cord Independence Measures (SCIM). Neurological recovery was assessed using ASIA impairment scale (AIS). We tried to correlate ambulatory ability of the patients with functional and neurological recovery.

Results:

Ambulatory ability of the patients improved significantly using WISCI II (P < 0.001) when admission and discharge scores were compared (1.4 ± 3.5 vs 7.6 ± 6.03). Similarly, functional (BI: 31.7 ± 20.5 vs 58.4 ± 23.7 and SCIM: 29.9 ± 15.1 vs 56.2 ± 20.6) and neurological recovery were found to be very significant (P < 0.001) when admission vs discharge scores were compared. Improvement in WISCI II scores was significantly correlated with improvement in neurological (using AIS scores) and functional status (using BI and SCIM scores) (P < 0.001).

Conclusions:

Significant improvement was seen in WISCI II, BI, and SCIM scores after in-patient rehabilitation. Improvement in WISCI II scores also significantly correlated with functional and neurological recovery.     

Real-time ultrasound brain perfusion imaging with analysis of microbubble replenishment in acute MCA stroke

Real-time ultrasound perfusion imaging (rt-UPI) allows visualization of microbubbles flowing through the cerebral microvasculature. We hypothesized that analysis of microbubble tissue replenishment would enable for characterization of perfusion deficits in acute middle cerebral artery (MCA) territory stroke. Twenty-three patients (mean age 70.2±13.2 years, 9 weeks) were included. Sequential images of bubble replenishment were acquired by transcranial rt-UPI at low mechanical index immediately after microbubble destruction. Different parameters were calculated from regions of interest (ROIs): real-time time to peak (rt-TTP), rise rate (β), and plateau (A) of acoustic intensity, and A × β was used as an index of blood flow. Results were compared with diffusion-weighted and perfusion magnetic resonance imaging. Parameters of rt-UPI had lower values in ROIs of ischemic as compared with normal tissue (β=0.58±0.40 versus 1.25±0.83; P=0.001; A=1.44±1.75 versus 2.63±2.31; P=0.05; A × β=1.14±2.25 versus 2.98±2.70; P=0.01). Real-time time to peak was delayed in ischemic tissue (11.43±2.67 versus 8.88±1.66 seconds; P<0.001). From the analysis of receiver operating characteristic curves, β and A × β had the largest areas under the curve with optimal cutoff values of β<0.76 and A × β<1.91. We conclude that rt-UPI with analysis of microbubble replenishment correctly identifies ischemic brain tissue in acute MCA stroke.     

Study to assess the effectiveness of modified constraint-induced movement therapy in stroke subjects: A randomized controlled trial

Background and Purpose:

The purpose of this study was to assess the effectiveness of modified constraint induced movement therapy (m-CIMT) in stroke subjects.

Materials and Methods:

A total of forty sub-acute stroke subjects were randomly assigned to either a m-CIMT (n = 20) or in a control group (n = 20). The m-CIMT group (14 men, 6 women; mean age = 55.2 years) consisted of structured 2 h therapy sessions emphasizing affected arm use, occurring 5 times/week for 2 weeks. A mitt was used to restrain the unaffected arm for 10 h/day for 2 week. The control group (11 men, 9 women; mean age = 56.4 years) consisted of conventional rehabilitation for time-matched exercise program. The outcome measures were evaluated at pre- and post-intervention by using the Wolf Motor Function Test (WMFT) and Fugl-Meyer assessment (FMA) of motor recovery after stroke.

Results:

After intervention significant effects were observed in m-CIMT group on WMFT (pre-test and post-test score was 28.04 ± 6.58, 13.59 ± 2.86; P =0.003). Similarly on FMA (pre- and post-test score was 31.15 ± 6.37, 55.7 ± 6.4; P = 0.00).

Conclusion:

There is a significant improvem ent in upper extremity function so it indicates that m-CIMT is effective in improving the motor function of the affected arm in stroke subjects. However, its long-term effect has not proved since there was no follow-up after intervention.     

Evaluation of the motor cortical excitability changes after ischemic stroke

Background:

We evaluated progressive changes in excitability of motor cortex following ischemic stroke using Transcranial Magnetic Stimulation (TMS).

Materials and Methods:

Thirty-one patients (24 men, 7 women; age 37.3 ± 8.2 years) were recruited and TMS was performed using Magstim 200 stimulator and a figure-of-eight coil. Resting motor threshold (RMT) was recorded from affected and unaffected hemispheres and motor evoked potential (MEP) was recorded from contralateral FDI muscle. Central motor conduction time (CMCT) was calculated using F wave method. All measurements were done at baseline (2^nd), 4^th, and 6^th week of stroke.

Results: Affected hemisphere:

MEP was recordable in 3 patients at baseline (all had prolonged CMCT). At 4 weeks, MEP was recordable in one additional patient and CMCT remained prolonged. At 6 weeks, CMCT normalized in one patient. RMT was recordable (increased) in 3 patients at baseline, in one additional patient at 4 weeks, and reduced marginally in these patients at 6 weeks.

Unaffected hemisphere:

MEP was recordable in all patients at baseline, and reduced significantly over time (2^nd week 43.52 ± 9.60, 4^th week 38.84 ± 7.83, and 6^th week 36.85 ± 7.27; P < 0.001). The CMCT was normal and remained unchanged over time.

Conclusion:

The increase in excitability of the unaffected motor cortex suggests plasticity in the post-stroke phase.     

Derangements in bone mineral parameters and bone mineral density in south Indian subjects on antiepileptic medications

Background:

Although there are reports describing the association of alternations of bone and mineral metabolism in epileptic patients with long-term anticonvulsant therapy, there are only limited Indian studies which have looked at this aspect.

Objectives:

This study was done to compare the prevalence of changes in bone mineral parameters and bone mineral density (BMD) in ambulant individuals on long-term anticonvulsant therapy with age- and body mass index (BMI)-matched healthy controls.

Materials and Methods:

There were 55 men (on medications for more than 6 months) and age- and BMI-matched 53 controls. Drug history, dietary calcium intake (DCI), and duration of sunlight exposure were recorded. Bone mineral parameters and BMD were measured.

Results:

The control group had a significantly higher daily DCI with mean ± SD of 396 ± 91 mg versus 326 ± 101 mg (P = 0.007) and more sunlight exposure of 234 ± 81 vs 167 ± 69 min (P = 0.05). BMD at the femoral neck was significantly lower in cases (0.783 ± 0.105 g/cm²) when compared to controls (0.819 ± 0.114 g/cm²). Majority of the patients (61%) had low femoral neck BMD (P = 0.04). There was no significant difference in the proportion of subjects with vitamin D deficiency (<20 ng/mL) between cases (n = 32) and controls (n = 37) (P = 0.234).

Conclusions:

Vitamin D deficiency was seen in both the groups in equal proportions, highlighting the existence of a high prevalence of this problem in India. Low femoral neck BMD found in cases may stress the need for supplementing calcium and treating vitamin D deficiency in this specific group. However, the benefit of such intervention has to be studied in a larger proportion of epileptic patients.     

Factors delaying hospital arrival of patients with acute stroke

Background:

Low rates of thrombolysis for ischemic stroke in India and other developing countries have been attributed to delays in presentation to the hospital.

Materials and Methods:

A prospective study was carried out during a 12-month period ending December 2012 in the department of Neurology, Malabar Institute of Medical Sciences, Kerala, India, to look for the factors contributing to delay in hospital arrival of patients with acute stroke. Patients and or their relatives were interviewed within 48 hours of admission using a structured questionnaire.

Results:

A total of 264 patients attending the emergency department were included. There were 170 men and 94 women. The mean age was 61.5 ± 12.4 years. A total of 67 (25%) patients presented within 4 hours of stroke onset. Factors associated with early arrival (multivariate logistic regression analysis) were distance 15 km or less from hospital (P 0.03, odds ratio (OR) 2.7), directly reaching the stroke department (P < 0.001, OR 9.7), history of coronary artery disease (P 0.001, OR 3.84), higher educational status (P 0.001, OR 3.7), and presence of hemiplegia (P 0.001, OR 5.5).

Conclusions:

We found a considerable delay in the early arrival of patients to our stroke department. Health promotion strategies to improve community awareness of early symptoms of stroke, education of local physicians about the importance of early referrals to the stroke centers, and wider availability and use of ambulance services are promising methods to help expedite presentation to hospital post stroke and thereby improve the management of stroke in India.     

MicroRNA-29b is a therapeutic target in cerebral ischemia associated with aquaporin 4

MicroRNA-29b (miR-29b) is involved in regulating ischemia process, but the molecular mechanism is unclear. In this work, we explored the function of miR-29b in cerebral ischemia. The level of miR-29b in white blood cells was evaluated in patients and mice after ischemic stroke. Brain infarct volume and National Institute of Health stroke scale (NIHSS) scores were analyzed to determine the relationship between miR-29b expression and the severity of stroke. The relationship of miR-29b and aquaporin-4 (AQP4) was further studied in mice. We found that miR-29b was significantly downregulated in stroke patients (P<0.05). MiR-29b level negatively associated with NIHSS scores (r=−0.349, P<0.01) and brain infarct volume (r=−0.321, P<0.05). In ischemic mice, miR-29b in the brain and blood were both downregulated (r=0.723, P<0.05). MiR-29b overexpression reduced infarct volume (49.50±6.55 versus 35.48±2.28 mm³, P<0.05), edema (164±4% versus 108±4%, P<0.05), and blood–brain barrier (BBB) disruption compared with controls (15±9% versus 7±3%, P<0.05). Aquaporin-4 expression greatly decreased after miR-29b overexpression (28±7% versus 11±3%, P<0.05). Dual-luciferase reporter system showed that AQP-4 was the direct target of miR-29b (P<0.05). We concluded that miR-29b could potentially predict stroke outcomes as a novel circulating biomarker, and miR-29b overexpression reduced BBB disruption after ischemic stroke via downregulating AQP-4.     

Sleep changes during prophylactic treatment of migraine

Aims:

To assess sleep quality in patients with primary headaches before and after prophylactic treatment using a validated sleep-screening instrument.

Materials and Methods:

A total of 147 patients, including 63 tension type headache (TTH) and 84 migraine patients were included. Patients were examined in terms of frequency and severity of headaches and sleep quality before and 12 weeks after prophylactic treatment with either propranolol or amitriptyline.

Results:

Baseline Visual Analogue Score (VAS) in migraine patients was 7.99 ± 1.39 compared with 6.86 ± 1.50 in TTH group (P < 0.001). VAS score after the first month of treatment was 6.08 ± 1.88 in migraine patients and 5.40 ± 1.61 in TTH (P = 0.023). VAS scores decreased after the third month of treatment to 4.32 ± 2.29 in migraine patients and 4.11 ± 1.66 in TTH patients (P = 0.344). The decrease was significant for patients treated with amitriptyline but not for those with propranolol. Baseline Pittsburgh Sleep Quality (PSQI) scores were 5.93 ± 2.43 in migraine patients and 6.71 ± 2.39 in TTH patients. Poor quality of sleep (PSQI ≥ 6) prior to prophylactic treatment was observed in 61.4% of migraine patients and in 77.7% of TTH patients. Comparison of PSQI scores before and 3 months following treatment showed significantly improved quality of sleep in all treatment groups; the greatest significance was detected in migraine patients with initial PSQI scores of ≥6 and treated with amitriptyline (P < 0.001).

Conclusions:

Increased understanding of routine objective sleep measures in migraine patients is needed to clarify the nature of sleep disturbances associated with primary headaches. This may in turn lead to improvements in headache treatments.     

Neuropsychiatric co-morbidities in non-demented Parkinson's disease

Objective:

To evaluate neuropsychiatric co-morbidities (depression, psychosis and anxiety) in non-demented patients with Parkinson''s disease (PD).

Background:

Non-motor symptoms like neuropsychiatric co-morbidities are common in Parkinson''s disease and may predate motor symptoms. Currently there is scarcity of data regarding neuropsychiatry manifestations in Indian patients with PD.

Methods:

In this cross-sectional study consecutive 126 non-demented patients with PD (MMSE ≥25) were enrolled. They were assessed using Unified Parkinson''s disease rating scale (UPDRS), Hoehn & Yahr (H&Y) stage, Schwab and England (S&E) scale of activity of daily life. Mini-international neuropsychiatric interview (MINI) was used for diagnosis of depression, psychosis and anxiety. Beck''s depression inventory (BDI), Brief psychiatric rating scale (BSRS) and Hamilton rating scale for anxiety (HAM-A) scales were used for assessment of severity of depression, psychosis and anxiety respectively.

Results:

Mean age and duration of disease was 57.9 ± 10.9 years and 7.3 ± 3.6 years respectively. At least one of the neuropsychiatric co-morbidity was present in 64% patients. Depression, suicidal risk, psychosis and anxiety were present in 43.7%, 31%, 23.8% and 35.7% respectively. Visual hallucinations (20.6%) were most frequent, followed by tactile (13.5%), auditory (7.2%) and olfactory hallucinations (1.6%). Patients with depression had higher motor disability (UPDRS-motor score 33.1 ± 14.0 vs 27.3 ± 13.3; and UPDRS-total 50.7 ± 21.8 vs 41.0 ± 20.3, all p values <0.05). Patients with psychosis were older (63.6 ± 8.0 years vs 56.1 ± 11.1 years, p < 0.05) and had longer duration of illness (8.6 ± 3.4 years vs 6.9 ± 3.5, p < 0.05).

Conclusions:

About two third patients with Parkinson''s disease have associated neuropsychiatric co-morbidities. Depression was more frequent in patients with higher disability and psychosis with longer duration of disease and older age. These co-morbidities need to be addressed during management of patients with PD.     

A pilot open-label trial of minocycline in patients with autism and regressive features

Background

Minocycline is a tetracycline derivative that readily crosses the blood brain barrier and appears to have beneficial effects on neuroinflammation, microglial activation and neuroprotection in a variety of neurological disorders. Both microglial activation and neuroinflammation have been reported to be associated with autism. The study was designed to evaluate the effects of minocycline treatment on markers of neuroinflammation and autism symptomatology in children with autism and a history of developmental regression.

Methods

Eleven children were enrolled in an open-label trial of six months of minocycline (1.4 mg/kg). Ten children completed the trial. Behavioral measures were collected and cerebrospinal fluid (CSF), serum and plasma were obtained before and at the end of minocycline treatment and were analyzed for markers of neuroinflammation.

Results

Clinical improvements were negligible. The laboratory assays demonstrated significant changes in the expression profile of the truncated form of brain derived neurotrophic factor (BDNF) (P = 0.042) and hepatic growth factor (HGF) (P = 0.028) in CSF. In serum, the ratio of the truncated BDNF form and α-2 macroglobulin (α-2 M), was also significantly lower (P = 0.028) while the mature BDNF/α-2 M ratio revealed no difference following treatment. Only the chemokine CXCL8 (IL-8) was significantly different (P = 0.047) in serum while no significant changes were observed in CSF or serum in chemokines such as CCL2 (MCP-1) or cytokines such as TNF-α, CD40L, IL-6, IFN-γ and IL-1β when pre- and post-treatment levels of these proteins were compared. No significant pre- and post-treatment changes were seen in the profiles of plasma metalloproteinases, putative targets of the effects of minocycline.

Conclusions

Changes in the pre- and post-treatment profiles of BDNF in CSF and blood, HGF in CSF and CXCL8 (IL-8) in serum, suggest that minocycline may have effects in the CNS by modulating the production of neurotrophic growth factors. However, in this small group of children, no clinical improvements were observed during or after the six months of minocycline administration.

Trial registration

{"type":"clinical-trial","attrs":{"text":"NCT00409747","term_id":"NCT00409747"}}NCT00409747     

Correlation between serum neuron specific enolase and functional neurological outcome in patients of acute ischemic stroke

Context:

The use of biomarkers to predict stroke prognosis is gaining particular attention nowadays. Neuron specific enolase (NSE), which is a dimeric isoenzyme of the glycolytic enzyme enolase and is found mainly in the neurons is one such biomarker.

Aims:

This study was carried out on patients of acute ischemic stroke with the aims to determine the correlation between NSE levels on the day of admission with infarct volume, stroke severity, and functional neurological outcome on day 30.

Materials and Methods:

Seventy five patients of acute ischemic stroke admitted in the Department of Medicine were included in the study. Levels of NSE were determined on day 1 using the human NSE ELISA kit (Alpha Diagnostic International Texas 78244, USA). Volume of infarct was measured by computed tomography (CT) scan using the preinstalled software Syngo (version A40A) of Siemen''s medical solutions (Forchheim, Germany). Stroke severity at admission was assessed using Glasgow coma scale (GCS) and functional neurological outcome was assessed using modified Rankin scale (mRS) on day 30.

Statistical Analysis Used:

Statistical analysis was performed using the SPSS software for windows version 15.0 (SPSS).

Results:

A positive correlation was found between concentration of NSE on day 1 and infarct volume determined by CT scan (r = 0.955, P < 0.001). A strong negative correlation was found between GCS at presentation and concentration of NSE on day 1 (r = −0.806, P < 0.001). There was a positive correlation between NSE levels at day 1 and functional neurological outcome assessed by mRS at day 30 (r = 0.744, P < 0.001).

Conclusions:

Serum levels of NSE in first few days of ischemic stroke can serve as a useful marker to predict stroke severity and early functional outcome. However, larger studies with serial estimation of NSE are needed to establish these observations more firmly.Key Words: Glasgow coma scale, infarct volume, ischemic stroke, modified Rankin scale, neuron specific enolase     

Time course of inflammatory cytokines in acute ischemic stroke patients and their relation to inter-alfa trypsin inhibitor heavy chain 4 and outcome

Background:

Biomarker for prognosis of stroke is urgently needed for the management of acute ischemic stroke (AIS) patients.

Objective:

To evaluate the course of inflammatory cytokines in AIS patients and its comparison with inter-alfa trypsin inhibitor heavy chain 4 (ITIH4) and outcome after AIS.

Materials and Methods:

A panel of 12 inflammatory cytokines and ITIH4 were estimated in serial blood samples collected at admission, 24 h, 48 h, 72 h, 144 h and at discharge of AIS patients (n = 5).

Results:

Out of the 12 cytokines, only interleukin (IL)-2, tumor necrosis factor-alfa (TNF-α), IL-10, IL-6, IL-1B and IL-8 were in the measurable range of the kit (10 pg/mL). We found high IL-2 at admission, which decreased (P < 0.05) in the follow-up samples. TNF-α initially increases (P < 0.05) at 24 h followed by gradual decrease (P < 0.05) after 72 h. IL-10 decreases initially (P < 0.05) till 72 h as compared with its level at admission and then increases (P < 0.05) after 144 h. Similarly, ITIH4 was down-regulated in the early 72 h followed by further increase with improvement of the patient. ITIH4 correlates with IL-10 and computed tomography scan infarct volume. Serum IL-6, IL-1B and IL-8 increased in the AIS patients, but did not show any pattern.

Conclusions:

Serial measurement of IL-10, IL-2 and TNF-α and ITIH4 may be useful for the follow-up of clinical outcome after AIS.     

Intranasal salvinorin A improves neurological outcome in rhesus monkey ischemic stroke model using autologous blood clot

Salvinorin A (SA) exerts neuroprotection and improves neurological outcomes in ischemic stroke models in rodents. In this study, we investigated whether intranasal SA administration could improve neurological outcomes in a monkey ischemic stroke model. The stroke model was induced in adult male rhesus monkeys by occluding the middle cerebral artery M2 segment with an autologous blood clot. Eight adult rhesus monkeys were randomly administered SA or 10% dimethyl sulfoxide as control 20 min after ischemia. Magnetic resonance imaging was used to confirm the ischemia and extent of injury. Neurological function was evaluated using the Non-Human Primate Stroke Scale (NHPSS) over a 28-day observation period. SA significantly reduced infarct volume (3.9 ± 0.7 cm³ vs. 7.2 ± 1.0 cm³; P = 0.002), occupying effect (0.3 ± 0.2% vs. 1.4 ± 0.3%; P = 0.002), and diffusion limitation in the lesion (−28.2 ± 11.0% vs. −51.5 ± 7.1%; P = 0.012) when compared to the control group. SA significantly reduced the NHPSS scores to almost normal in a 28-day observation period as compared to the control group (P = 0.005). Intranasal SA reduces infarct volume and improves neurological outcomes in a rhesus monkey ischemic stroke model using autologous blood clot.     

Correlation of the Beta-Trace Protein and Inflammatory Cytokines with Magnetic Resonance Imaging in Chronic Subdural Hematomas : A Prospective Study

Objective

Magnetic resonance imaging (MRI) of chronic subdural hematoma (CSDH) detects various patterns, which can be attributed to many factors. The purpose of this study was to measure the level of interleukin-6 (IL-6), interleukin-8 (IL-8), and highly specific protein [beta-trace protein (βTP)] for cerebrospinal fluid (CSF) in CSDHs, and correlate the levels of these markers with the MRI findings.

Methods

Thirty one patients, treated surgically for CSDH, were divided on the basis of MRI findings into hyperintense and non-hyperintense groups. The concentrations of IL-6, IL-8, and βTP in the subdural fluid and serum were measured. The βTP was considered to indicate an admixture of CSF to the subdural fluid if βTP in the subdural fluid (βTP_SF)/βTP in the serum (βTP_SER)>2.

Results

The mean concentrations of IL-6 and IL-8 of the hyperintense group (n=17) of T1-WI MRI were 3975.1±1040.8 pg/mL and 6873.2±6365.4 pg/mL, whereas them of the non-hyperintense group (n=14) were 2173.5±1042.1 pg/mL and 2851.2±6267.5 pg/mL (p<0.001 and p=0.004). The mean concentrations of βTP_SF and the ratio of βTP_SF/βTP_SER of the hyperintense group (n=13) of T2-WI MRI were 7.3±2.9 mg/L and 12.6±5.4, whereas them of the non-hyperintense group (n=18) were 4.3±2.3 mg/L and 7.5±3.9 (p=0.011 and p=0.011).

Conclusion

The hyperintense group on T1-WI MRI of CSDHs exhibited higher concentrations of IL-6 and IL-8 than non-hyperintense group. And, the hyperintese group on T2-WI MRI exhibited higher concentrations of βTP_SF and the ratio of βTP_SF/βTP_SER than non-hyperintense group. These findings appear to be associated with rebleeding and CSF admixture in the CSDHs.     

Systematic review of long-term Xingnao Kaiqiao needling effcacy in ischemic stroke treatment

OBJECTIVE:

To systematically evaluate the long-term effect and safety of Xingnao Kaiqiao needling method in ischemic stroke treatment.

DATA RETRIEVAL:

We retrieved relevant random and semi-random controlled trials that used the Xingnao Kaiqiao needling method to treat ischemic stroke compared with various control treatments such as conventional drugs or other acupuncture therapies. Searched databases included China National Knowledge Infrastructure, Weipu Information Resources System, Wanfang Medical Data System, Chinese Biomedical Literature Database, Cochrane Library, and PubMed, from May 2006 to July 2014.

SELECTION CRITERIA:

Two authors independently conducted literature screening, quality evaluation, and data extraction. The quality of articles was evaluated according to the Cochrane Reviewers’ Handbook 5.1, and the study was carried out using Cochrane system assessment methods. RevMan 5.2 was used for meta-analysis of the included studies.

MAIN OUTCOME MEASURES:

Mortality rate, recurrence rate, and disability rate were observed.

RESULTS:

Nine randomized and semi-randomized controlled trials treating 931 cases of ischemic stroke were included in this review. Meta-analysis results showed that there were no significant differences in mortality reduction (risk ratio (RR) = 0.58, 95% confidence interval (CI): 0.17–1.93, Z = 0.89, P = 0.37) or recurrence rate (RR = 0.55, 95%CI: 0.18–1.70, Z = 1.04, P = 0.30) of ischemic stroke patients between the Xingnao Kaiqiao needling and control treatment groups. However, the Xingnao Kaiqiao needling method had a tendency towards higher efficacy in mortality reduction and recurrence rates. The Xingnao Kaiqiao needling method was significantly better than that of the control treatment in reducing disability rate (RR = 0.51, 95%CI: 0.27–0.98, Z = 2.03, P < 0.05).

CONCLUSION:

The Xingnao Kaiqiao needling method has a better effect than control treatment in reducing disability rate. The long-term effect of Xingnao Kaiqiao needling against ischemic stroke is better than that of control treatment. However, the limitations of this study limit the strength of the conclusions. Randomized controlled trials with a strict, reasonable design, and multi-center, large-scale samples and follow-up are necessary to draw conclusions about Xingnao Kaiqiao needling.     

Women with epilepsy and infertility have different reproductive hormone profile than others

Purpose:

One-third of women with epilepsy (WWE) may experience infertility (failure to conceive after 12 months of regular unprotected intercourse). We aimed to compare the hormone profile of WWE and infertility (WWE-I) with that of WWE who had conceived earlier (WWE-F).

Materials and Methods:

In the Kerala Registry of Epilepsy and Pregnancy, we compared the clinical and hormone profile of 50 WWE-I and 40 age-matched WWE-F. Subjects were examined and blood samples were drawn in follicular phase (1-14 days) for 21 WWE-I and 18 WWE-F, in luteal phase (15-30 days) for 23 WWE-I and 15 WWE-F and beyond 30 days for 6 WWE-I and WWE-F who had irregular cycles.

Results:

The two groups were comparable regarding physical, epilepsy syndrome, duration of epilepsy, body mass index, and serum cholesterol levels. Menstrual periods were irregular for 6 WWE-I and 5 WWE-F. The WWE-I group (compared to the WWE-F group) had significantly (P < 0.01) higher levels of dehydroepiandrostenedione (2.0 ± 1.7 ug/mL vs. 1.0 ± 0.7 ug/mL) and luteinizing hormone-LH (26.4 ± 37.3 mIU/mL vs. 9.9 ± 14.5 mIU/mL) and lower levels of progesterone (5.2 ± 9.2 ng/mL vs. 10.4 ± 13.4 ng/mL). There was no significant difference in the levels of FT3, FT4, thyroid stimulating hormone, prolactin, follicle-stimulating hormone (FSH), progesterone, testosterone, or androstenedione levels. The WWE-I had 8.5 times higher risk (95% confidence interval 1.2-59.9) of abnormal LH/FSH ratio. WWE who were on antiepileptic drugs (AEDs) (compared to WWE who were not on AEDs) had higher risk of elevated LH/FSH ratio.

Conclusion:

The hormone profile of WWE-I is significantly different from that of WWE-F. These variations need to be interpreted with caution as a causal relationship to epilepsy or use of antiepileptic drugs need to be established through further studies.Key Words: Antiepileptic drug, infertility, pregnancy, reproductive endocrine