Background
Retrospective studies suggested that cerebral microbleeds (MB) on magnetic resonance images (MRI) increase risk of intracerebral haemorrhage (ICH).
Objective
To compare the benefit of ...anti-thrombotic agents in stroke prevention (absolute risk reduction 2.49 –6 %) versus risk of ICH in ischaemic stroke patients with MB.
Materials and methods
We prospectively studied patients admitted consecutively for acute ischaemic stroke between 1999 and 2004. MB on MRI were documented. Primary end points were subsequent ICH, recurrent cerebral infarct (CI) and mortality.
Results
A total of 908 patients were recruited. MB were identified in 252 (27.8 %) patients. Mean follow-up period was 26.6 ± 15.4 months. Risk of subsequent ICH increased significantly with quantity of MB: 0.6 % (no MB), 1.9 % (1 MB), 4.6 % (2–4 MB) and 7.6 % (≥ 5 MB) (p < 0.001). There was also a significant increase in mortality from ICH: 0.6 %, 0.9 %, 1.5 % and 3.8 % respectively (p = 0.054). Rate of recurrent CI was 9.6 %, 5.6 %, 21.5 % and 15.2 % respectively (p = 0.226). Mortality from CI and myocardial infarction did not increased with quantity of MB. Survival analyses showed that age, presence of MB, mixed cortical-subcortical distribution of MB were independent predictors of subsequent ICH.
Conclusion
Risk and mortality of ICH increased with quantity of MB. As tendency to recurrent CI exceed that of ICH, anti-thrombotic agents are still warranted. However, in patients with ≥ 5 MB, the high risk and mortality of ICH seem to outweigh the modest benefit of antithrombotic agents. Extra precautions should be taken to minimize risk of ICH. Further studies in patients on Coumadin and assessment of functional outcome are warranted to support these preliminary findings.
Background and purpose
Studies mostly use the analysis of heart rate variability to measure cardiovascular autonomic regulation in ischemic stroke. Besides power spectral analysis of heart rate ...variability, this study sought to determine whether autonomic function was impaired during different phases in ischemic stroke by Ewing's battery of autonomic function tests.
Methods
Ninety-four patients with ischemic stroke (34 patients in acute phase and 60 patients in chronic phase, average six-months after stroke onset) and thirty-seven elderly controls were recruited. Ewing's battery autonomic function tests and power spectral analysis of heart rate variability were performed in all the subjects.
Results
From power spectral analysis of heart rate variability, stroke patients of both acute and chronic phases had significantly lower low frequency power spectral density than controls. From Ewing's battery of autonomic function tests, patients in acute phase showed impairment in two parasympathetic tests (Valsalva ratio: P = 0·002; heart rate response to deep breathing: P < 0·001) and those in chronic phase showed impairment in all parasympathetic tests (all P < 0·05) in comparison with controls.
Conclusions
The comprehensive assessment indicates that autonomic dysfunction occurs in acute phase of ischemic stroke and may persist up to six-months after stroke. Parasympathetic dysfunction rather than sympathetic dysfunction is predominant after ischemic stroke.
BACKGROUND AND PURPOSE—Central autonomic dysfunction increases stroke morbidity and mortality. We aimed to investigate whether poststroke autonomic dysfunction graded by Ewing battery can predict ...clinical outcome.
METHODS—In this prospective observational study, we assessed autonomic function of ischemic stroke patients within 7 days from symptom onset by Ewing battery. On the basis of the magnitude of autonomic dysfunction, we stratified patients into significant (definite, severe, or atypical) or minor (normal or early) autonomic function impairment groups and correlated the impairment with the 3-month modified Rankin Scale score (good outcomemodified Rankin Scale score 0≈2; poor outcomemodified Rankin Scale score 3≈6).
RESULTS—Among the 150 patients enrolled (mean age, 66.4±9.9 years; 70.7% males), minor autonomic dysfunction was identified in 36 patients (24.0%), and significant autonomic dysfunction was identified in 114 patients (76.0%) based on Ewing battery. In 3 months, a poor functional outcome was found in 32.5% of significant group patients compared with 13.9% in the minor group (P=0.031). Crude odds ratios of the magnitude of autonomic dysfunction and 3-month unfavorable functional outcome after acute ischemic stroke were 2.979 (95% confidence interval, 1.071–8.284; P=0.036). After adjusting for confounding variables with statistical significance between the 2 functional outcome subgroups identified in univariate analysis (including sex and National Institutes of Health Stroke Scale score on admission), the magnitude of autonomic dysfunction still independently predicted an unfavorable outcome, with an odds ratio of 3.263 (95% confidence interval, 1.141–9.335; P=0.027).
CONCLUSIONS—Autonomic dysfunction gauged by Ewing battery predicts poor functional outcome after acute ischemic stroke.
•Two-week course of carbamazepine (CBZ) treatment could induce auto-induction of CBZ metabolism.•Single-dose of CBZ/Gastrodiae Rhizoma (GR) treatment increases the duration of in vivo time but a ...lower maximum concentration.•A 2-week course of CBZ/GR alters the metabolism of CBZ and carbamazepine-10,11-epoxide(CBZE).•Concurrent treatment of GR could mitigate the auto-induction of CBZ in the two-week course of CBZ/GR treatment.
Gastrodiae Rhizoma (GR), is a traditional Chinese Medicine that has been used for neurological disorders, including epilepsy. Epilepsy patients may be treated with adjunctive therapy of GR with antiepileptic drugs (AEDs). In particular, carbamazepine (CBZ) is of high potential to interact with concurrent treatment of Chinese Medicine. This study was to investigate the herb-drug interactions of GR and CBZ, an AED, through pharmacokinetic approach in rats.
We adopted a high-performance liquid chromatography (HPLC) system to quantify the plasma level of CBZ and its metabolite (carbamazepine-10, 11-epoxide, CBZE). The method was validated as per instructions under United States Food and Drug Administration (USFDA) guidance. For the herb-drug interaction study, rats were randomly divided into four different treatment groups: single-dose CBZ treatment, single-dose CBZ/GR treatment, 2-week course of CBZ treatment and 2-week course of CBZ/GR treatment.
Our results demonstrated the auto-induction of CBZ metabolization when comparing single-dose with 2-week course of CBZ treatment. Pharmacokinetic interactions were noted in concomitant use of GR with CBZ by comparing two single-dose treatments (CBZ versus CBZ/GR). Our data showed that GR increased the mean residence time (MRT0-t) and the time taken to reach the maximum concentration (Tmax) of CBZ in single-dose of CBZ/GR treatment. The maximum drug concentration (Cmax) of CBZ was reduced in single-dose CBZ/GR treatment. When comparing the 2-week course of CBZ treatment with the 2-week course of CBZ/GR treatment, the MRT0-t and half-life of CBZ were increased. The AUC0-t, the Cmax and the half-life of CBZE were increased.
CBZ/GR treatment may reduce the auto-induction of CBZ over 2 weeks. While the reduction of auto-induction could enhance the therapeutic effects of CBZ, it could also lead to an increase in neurological side effects and non-neurological adverse effects. Our results provided preclinical evidence of herb-drug interaction, which may have implications for epilepsy patients treated with GR.
Background and Objective
Drug–drug interactions between direct oral anticoagulants (DOAC) and antiseizure medications via the cytochrome P450 (CYP) or the P-glycoprotein (P-gp) systems may lead to ...under-anticoagulation. The clinical relevance of these interactions is unclear. We aimed to elucidate the risk of thromboembolism with concurrent DOAC and CYP/P-gp modulating antiseizure medications.
Methods
In this propensity score-weighted population-based retrospective cohort study, we used competing risk regression analyses to determine the risks of ischemic stroke, venous thromboembolism, and death in DOAC recipients taking CYP/P-gp-modulating antiseizure medications (phenytoin, valproate, levetiracetam, carbamazepine, or phenobarbital) versus those taking CYP/P-gp-neutral antiseizure medications (pregabalin, gabapentin, or clobazam). We also performed secondary analyses for the epilepsy and atrial fibrillation subgroups.
Results
Among DOAC users, CYP/P-gp-modulating antiseizure medications were collectively associated with an increased risk of ischemic stroke (adjusted hazard ratio 1.28, 95% confidence interval 1.05–1.57,
p
= 0.017). In addition, phenytoin (adjusted hazard ratio 1.34, 95% confidence interval 1.07–1.68,
p
= 0.011) and valproate (adjusted hazard ratio 1.38, 95% confidence interval 1.10–1.74,
p
= 0.006) were associated with increased mortality. In the epilepsy subgroup, the risk of ischemic stroke and venous thromboembolism did not differ between CYP/P-gp-modulating and CYP/P-gp-neutral antiseizure medications.
Conclusions
Although CYP/P-gp-modulating antiseizure medications were associated with an increased risk of ischemic stroke when paired with DOAC in the primary analysis, such a phenomenon was not found among patients with epilepsy who took phenytoin, valproate, or levetiracetam with DOAC. Therefore, these antiseizure medication options among patients with epilepsy with concurrent DOAC should not be restricted solely based on their potential drug–drug interactions. Yet, the increased mortality during concurrent use of DOAC with phenytoin or valproate might call for caution.
Aim
The anterior nucleus of the thalamus (ANT) has been one of the deep brain stimulation (DBS) targets for drug‐resistant epilepsy. This study aims to investigate the control of seizures among ...patients with ANT DBS for epilepsy. We have pioneered DBS for epilepsy in Hong Kong since 2015 and this study aims to report the long‐term outcomes from a prospective cohort.
Methods
This is a prospective cohort study of ANT DBS for adult patients with drug‐resistant epilepsy, who are unsuitable for resective epilepsy surgery.
Results
Six patients (3 females and 3 males, mean age 31.3) received bilateral ANT DBS in a tertiary university hospital from 2015 to 2018 (one in 2015, two in 2017 and three in 2018). Both frontal transventricular and parietal approaches were used. The active contacts were selected based on the closest Euclidean distance to the mammillothalamic tract and ANT junction. Five of the six cases (83.3%) achieved greater than 50% reduction in seizures after the operations. The median percentage of reduction in seizures was 58.5% at 3 years after DBS (range, 32.7%–80%). Overall, there was a trend of improving seizure control rate from year 1 to year 6 after the ANT DBS operations.
Conclusions
This is the first report of ANT DBS for drug‐resistant epilepsy in Hong Kong. The results are encouraging. ANT DBS for drug‐resistant epilepsy is effective and sustained in long term. The treatment option of ANT DBS should be considered in suitable candidates with drug‐resistant epilepsy in our locality.
Background
Stroke not only substantially increases the risk of incident dementia early after stroke but also the risk remains elevated years after.
Aim
We aimed to determine the risk factors of ...dementia onset more than three to six months after stroke or transient ischemic attack.
Methods
This is a single-center prospective cohort study. We recruited consecutive subjects with stroke/transient ischemic attack without early-onset dementia. We conducted an annual neuropsychological assessment for five years. We investigated the association between baseline demographic, clinical, genetic (APOEɛ4 allele), and radiological factors as well as incident recurrent stroke with delayed-onset dementia using Cox proportional hazards models.
Results
In total, 1007 patients were recruited, of which 88 with early-onset dementia and 162 who lost to follow-ups were excluded. Forty-nine (6.5%) out of 757 patients have incident delayed-onset dementia. The presence of ≥3 lacunes, history of ischemic heart disease, history of ischemic stroke, and a lower baseline Hong Kong version of the Montreal Cognitive Assessment (MoCA) score were significantly associated with delayed-onset dementia. APOEɛ4 allele, medial temporal lobe atrophy, and recurrent stroke were not predictive.
Conclusion
The presence of ≥3 lacunes, history of ischemic heart disease, history of ischemic stroke, and a lower baseline MoCA score are associated with delayed-onset dementia after stroke/transient ischemic attack.
Objective
Understanding how symptomatic intracranial atherosclerotic disease (ICAD) evolves with current medical therapy may inform secondary stroke prevention.
Methods
In a prospective ...academic‐initiated study, we recruited 50 patients (mean age = 63.4 ± 9.0 years) with acute strokes attributed to high‐grade (≥70%) intracranial atherosclerotic stenosis for 3‐dimensional rotational angiograms before and after intensive medical therapy for 12 months. Treatment targets included low‐density lipoprotein ≤ 70mg/dl, glycosylated hemoglobin (HbA1c) ≤ 6.5%, and systolic blood pressure ≤ 140 mmHg. We analyzed infarct topography and monitored microembolic signal in recurrent strokes. The reference group was a published cohort of 143 ICAD patients.
Results
Overall, the stenoses regressed from 79% at baseline (interquartile range IQR = 71–87%) to 63% (IQR = 54–74%) in 1 year (p < 0.001). Specifically, the qualifying lesions (n = 49) regressed (stenosis reduced >10%) in 24 patients (49%), remained quiescent (stenosis same or ±10%) in 21 patients (43%), and progressed (stenosis increased >10%) in 4 patients (8%). There was no difference in intensity of risk factor control between groups of diverging clinical or angiographic outcomes. Higher HbA1c at baseline predicted plaque regression at 1 year (odds ratio = 4.4, 95% confidence interval = 1.4–14.5, p = 0.006). Among the 6 patients with recurrent strokes pertaining to the qualifying stenosis, 5 patients had solitary or rosarylike acute infarcts along the internal or anterior border zones, and 2 patients showed microembolic signals in transcranial Doppler ultrasound.
Interpretation
A majority of symptomatic high‐grade intracranial plaques had regressed or remained quiescent by 12 months under intensive medical therapy. Artery‐to‐artery thromboembolism with impaired washout at border zones was a common mechanism in stroke recurrence. Ann Neurol 2015;77:478–486
Abstract only
Introduction:
We compared the morphology of intracranial atherosclerotic plaques in the anterior versus posterior circulation, using three-dimensional rotational angiography (3DRA).
...Methods:
We prospectively recruited adult patients with acute ischemic stroke or transient ischemic attack attributed to high-grade (60-99%), atherosclerotic intracranial stenosis as confirmed by 3DRA. We assessed the plaque morphology in 3DRA, including the percentage of luminal stenosis, smooth/irregular/ulcerative plaque surface contour, plaque thickness, length, eccentricity, upstream plaque shoulder angulation, longitudinal distribution of the maximal stenosis, and adjoining branch atheromatous disease (BAD). We compared characteristics of patients with middle cerebral artery-M1 (MCA-M1) and basilar artery (BA) plaques, and the plaque morphology in the two subgroups.
Results:
Overall, 164 and 17 patients respectively with MCA-M1 and BA plaques were analyzed, with similar age (medians 60 versus 62 years), sex (male 64.6 versus 52.9%) and history of common vascular risk factors. The percentage of luminal stenosis (medians 77 versus 81%), proportion of smooth/irregular/ulcerative plaque surface contour, upstream plaque shoulder angulation (32.1 versus 25.8 °), longitudinal distribution of the maximal stenosis, and presence of adjoining BAD (56.7 versus 64.7%) were similar between MCA-M1 and BA plaques. However, BA plaques were thicker (1.5 versus 1.3mm; p=0.03) and longer (16.4 versus 8.4mm; p<0.001), but less likely eccentric (70.6 versus 88.4%; p=0.039).
Conclusions:
There were differences in the morphology of symptomatic atherosclerotic plaques in anterior and posterior circulations, independent of demographics and common vascular risk factors. Different artery geometry and the hemodynamics may underlie such differences.
PDF
