Epileptic seizures after a first stroke: the Oxfordshire Community Stroke Project.

OBJECTIVE: To describe the immediate and long term risk of epileptic seizures after a first ever stroke. DESIGN: Cohort study following up stroke survivors for 2 to 6.5 years; comparison with age specific incidence rates of epileptic seizures in the general population. SETTING: Community based stroke register. SUBJECTS: 675 patients with a first stroke, followed up for a minimum of 2 years. MAIN OUTCOME MEASURES: Occurrence of single and recurrent seizures. RESULTS: 52 patients had one or more post stroke seizures; in 25 the seizures were recurrent. The 5 year actuarial risk of a post stroke seizure in survivors (excluding 19 patients with a history of epilepsy and 3 patients in whom the seizure occurred shortly before death from another cause) was 11.5% (95% confidence interval 4.8% to 18.2%). The relative risk of seizures, in comparison with the general population, was estimated at 35.2 in the first year after stroke and 19.0 in year 2. The risk of seizures was increased in survivors of subarachnoid and intracerebral haemorrhage (hazard ratio for intracranial haemorrhage v cerebral infarction 10.2 (3.7 to 27.9)). The risk of seizures after ischaemic stroke was substantial only in patients presenting with severe strokes due to total anterior circulation infarction. Only 9 of 295 patients (3%) independent one month after stroke suffered a seizure between 1 month and 5 years (actuarial risk 4.2% (0.1% to 8.3%)). CONCLUSION: Stroke patients have about an 11.5% risk of single or recurrent seizures in the first 5 years after a stroke. Patients with more severe strokes or haemorrhagic strokes are at higher risk.     

Pentylenetetrazol (PTZ)-kindling development in intact and subcortical structure lesioned rats

Kindling was induced in male wistar rats (280-320 g) by daily ip injections of PTZ in subthreshold doses (30 mg/kg). Repeated administration of PTZ to animals resulted in developing of enhanced seizures and also enhanced seizure susceptibility which could be sustained for a long time (6 months) after last seizure paroxysm. The lesioned hippocampus retarded the manifestation of PTZ kindling, where as lesioned caudate nuclei increased the seizure kindling development. Results also revealed hippocampus as a determinant structure in PTZ kindling formation, which stabilize the epileptic manifestations and make them chronic, at the same time caudate nuclei retarded the epileptic seizures stabilization. This role may be only antiepileptic, and not anti-kindling as is known for caudate nuclei.     

I131内放射治疗对成人恶性脑胶质瘤癫痫发作的影响

目的：探讨内放射治疗对胶质瘤引起的癫痫的影响。方法：回顾性分析2004年后利用I131内放射治疗的成人幕上恶性脑胶质瘤合并有癫痫发作的患者23例,统计其在治疗前1月及治疗后1月、2月时的癫痫发作频率和类型,并分析肿瘤体积变化与发作频率变化的关系。结果：治疗后1月癫痫发作无明显改变,治疗后2个月癫痫发作明显减少,13例无癫痫发作,另外10例有发作患者频率也明显下降,其中肿瘤缩小超过1／2者78％无癫痫发作。结论：I131内放射治疗的成人幕上恶性脑胶质瘤可以明显减少患者的癫痫发作。     

I131内放射治疗对成人恶性脑胶质瘤癫痫发作的影响

目的:探讨内放射治疗对胶质瘤引起的癫痫的影响.方法:回顾性分析2004年后利用I131内放射治疗的成人幕上恶性脑胶质瘤合并有癫痫发作的患者23例,统计其在治疗前1月及治疗后1月、2月时的癫痫发作频率和类型,并分析肿瘤体积变化与发作频率变化的关系.结果:治疗后1月癫痫发作无明显改变,治疗后2个月癫痫发作明显减少,13例无癫痫发作,另外10例有发作患者频率也明显下降,其中肿瘤缩小超过1/2者78％无癫痫发作.结论:I131内放射治疗的成人幕上恶性脑胶质瘤可以明显减少患者的癫痫发作.     

Restenosis begets restenosis: implications for stent selection

Background. Identifying the risk for restenosis is of critical importance in the stent selection process of patients undergoing percutaneous coronary intervention (PCI). Therefore, we sought to determine if a history of clinical recurrence (CR) after PCI increases the risk of CR after treatment of a de novo lesion in another coronary artery. Methods. We retrospectively analysed all 12,763 patients who underwent PCI between 1993 and 2004 and selected patients with two or more interventions in two different native vessels. These patients were divided into two groups: patients without CR, and patients with CR after the first PCI. Clinical recurrence was defined as revascular-isation of the target vessel by either PCI or CABG within one year. Results. A total of 1010 patients with two or more interventions in two different native vessels were identified: 727 patients without and 283 patients with CR after the first PCI. Baseline patient characteristics and conventional risk factors were comparable between the two groups. Patients with a history of CR had a higher risk of CR after a second intervention in a second vessel (OR=3.4, 95% CI=2.3 to 4.9). A total of 112 patients also had a third intervention in a third native vessel: 12 patients with two CR, 30 patients with one CR and 70 patients with no CR after the first two interventions. CR rates in these patients were 50, 17 and 3%, respectively (p<;0.001). Conclusion. Patients with a history of CR have a markedly increased risk of developing CR after a second or third PCI in a different coronary artery. Therefore, in the decision-making process on whether to use a bare metal stent or drug-eluting stent, the history of CR is a simple and powerful aid. (Neth Heart J 2008;16:376-81.)     

The effectiveness of anti-inflammatory and anti-seizure medication for individuals with single enhancing lesion neurocysticercosis: A meta-analysis and expert group-based consensus recommendations

Single brain enhancing lesions (SEL) are the most common presentation of neurocysticercosis (NCC) observed on neuroimaging in people presenting with epileptic seizures not only on the Indian sub-continent and in travelers returning from cysticercosis-endemic regions, but are also present in other parts of the world.The aim of this study, which consisted of a systematic review (CRD42019087665), a meta-analysis and an expert group consultation, was to reach consensus on the best anti-seizure medication and anti-inflammatory treatment for individuals with SEL NCC.Standard literature review methods were used. The Cochrane risk of bias tool was used and random effects model meta-analyses were performed. The quality of the body of evidence was rated using GRADE tables. The expert committee included 12 gender and geographically balanced members and recommendations were reached by applying the GRADE framework for guideline development.The 1–1.5-year cumulative incidence of seizure recurrence, cyst resolution or calcification following anti-seizure medication (ASM) withdrawal was not statistically different between ASM of 6, 12 or 24 months. In contrast, in persons whose cyst calcified post treatment, longer ASM decreased seizure recurrence. The cumulative incidence ratio (CIR) 1–1.5 years after stopping ASM was 1.79 95% CI: (1.00, 3.20) for patients given 6 versus 24 months treatment.Anti-inflammatory treatment with corticosteroids in patients treated with ASM compared to patients treated with ASM only showed a statistically significant beneficial effect on seizure reduction (CIR 0.44, 95% CI 0.23, 0.85) and cyst resolution (CIR 1.37, 95%CI: 1.07, 1.75).Our results indicate that ASM in patients with SEL NCC whose cysts resolved can be withdrawn, while patients whose cysts calcified seem to benefit from prolonged anti-seizure medication. Additional corticosteroid treatment was found to have a beneficial effect both on seizure reduction and cyst resolution.     

癫痫与认知功能

癫痫是神经系统最常见的疾病之一,以反复的自发发作为特征,还伴随着对认知,心理以及社交的影响。相比一般人群,癫痫患者更容易罹患认知和行为的障碍,认知障碍在新诊断的部分或者全面性癫痫发作的成人癫痫患者中均有报道。癫痫发作类型、病因、神经病理、发作类型、发作年龄、社会心理问题等一系列因素都和认知功能障碍相关,而且目前癫痫主要的治疗方法（如抗癫痫药物治疗和外科手术）也和认知及行为障碍相关。对于这些与治疗相关的副作用,临床治疗应该警惕并且尽量避免或者缩小负面的影响。本文从生物学因素、心理社会学因素及治疗相关的因素三个方面综述了癫痫与认知障碍之间的关系,为临床治疗和预防癫痫提供指导。     

Higher risk of seizures in offspring of mothers than of fathers with epilepsy.

Seizure risk has consistently been found to be higher in offspring of mothers than of fathers with epilepsy. This pattern cannot be explained by any simple genetic model. The present study examined the possibility that the pattern arises from differences between affected mothers and fathers in the characteristics of their epilepsy that influence offspring seizure risk. The study population comprised 687 offspring of parents with epilepsy from the Rochester-Olmsted County Record Linkage Project. Cumulative incidences of unprovoked seizures to age 25 were 8.7% and 2.4% in offspring of affected mothers and fathers, respectively. Cox proportional hazards analysis was used to calculate rate ratios (RRs) for unprovoked seizures in offspring. In the univariate analysis, risk of unprovoked seizures was higher if the affected parent was the mother (RR = 2.8, 95% confidence interval [ci] 1.1-7.2) or if the parent's onset was before age 20 (RR = 2.5, 95% ci 1.1-5.9), but there was no effect on offspring risk of either parent's etiology (idiopathic vs. remote symptomatic) or parent's seizure type (generalized vs. partial). These findings were not substantially changed in the multivariate analysis. Thus, differences between affected mothers and fathers in these characteristics did not account for the higher risk in offspring of affected mothers. Anticonvulsant use during pregnancy was not associated with increased offspring seizure risk.(ABSTRACT TRUNCATED AT 250 WORDS)     

Incidence of seizures and EEG abnormalities among offspring of epileptic patients

Summary The marriage rate of epileptic patients was 62% in males und 78% in females. Compared with the rates in the general population, the male patients had a 15% lower rate, but there was no difference in females. There were 263 patients with at least one offspring selected for the study. There were 243 sons and 272 daughters (506 total, 1.9 per patient). Distribution by types of seizure was awakening grand mal, absence or myoclonic petit mal in 24%, grand mal with no aura in 21%, grand mal during sleep in 23%, diffuse grand mal in 7%, grand mal with aura in 13%, psychomotor seizure in 9%, and focal seizure in 3%. The probands were composed of 79% idiopathic and 21% symptomatic in pathogenetic classification. An epileptic EEG abnormality was demonstrated in 22% of male and 44% of female probands.The incidence of seizures among offspring was 2.4% (4.2% age-corrected) in a narrow sense (epilepsy) and 9.1% in a broad sense including febrile convulsions. The latter morbidity was 11.0% for the idiopathic and 3.2% for the symptomatic group; 11.0% for female and 6.9% for male probands; 10.2% for sons and 8.1% for daughters. The figure was higher for the probands with the age range at onset of seizure of 0–4 years (20.6%) and 20–29 years (12.6%) than for those with other age ranges; higher for those with awakening grand mal, absence, myoclonic petit mal, or grand mal with no aura than for those with other types of seizure; and higher for those with family history of epilepsy than those without it.Possible correlation of types of seizure between probands and offspring was demonstrated. Thirty-seven percent of offspring exhibited epileptic EEG abnormalities, and the ratio of epileptic EEG abnormalities to clinical manifestation is about 4:1.Possible existence of familial aggregation of EEG abnormalities and of two kinds of families with large or small epileptic predisposition was indicated.The importance of the role of hereditary and environmental factors in epileptic pathogenesis is proved, and the results of an investigation of congenital malformation among offspring of epileptic mothers are presented. These results were considered to be useful for genetic counseling of epileptic patients.     

Prognostic index for recurrence of seizures after remission of epilepsy. Medical Research Council Antiepileptic Drug Withdrawal Study Group.

OBJECTIVES--To develop and test a prognostic index for the recurrence of seizures after a minimum remission of seizures of two years in people with a history of epilepsy. DESIGN--Information from a large prospective randomised study of withdrawal of antiepileptic drugs was used to identify clinical and treatment factors of prognostic importance in determining the recurrence of seizures. A split sample approach was used to test the internal validity of predictions made on the basis of identified prognostic factors. SETTING--Centres in six European countries. MAIN OUTCOME MEASURES--Comparison of predicted and observed rates of recurrence of seizure. SUBJECTS--1013 patients randomised to the Medical Research Council study for antiepileptic drug withdrawal. RESULTS--The Cox proportional hazards model identified several factors that increased the risk of seizures recurring. These included being 16 years or older; taking more than one antiepileptic drug; experiencing seizures after starting antiepileptic drug treatment; a history of primary or secondarily generalised tonic-clonic seizures; a history of myoclonic seizures; and having an abnormal electroencephalogram. The risks of seizures recurring decreased with increasing time without seizures. The model allowed estimation of the risk of seizures recurring in the next one and two years under the policies of continued antiepileptic drug treatment and slow withdrawal of drugs. Split sample validation suggested that the model was well calibrated. CONCLUSION--The model is currently the best available aid for counselling the many patients in the community with epilepsy currently in remission who seek advice about the risks of seizures recurring if they stop antiepileptic drug treatment. The model requires validation in a broad population of patients, and such studies are in progress.     

Psychiatric Disorders after Epilepsy Diagnosis: A Population-Based Retrospective Cohort Study

Background

Psychiatric manifestations after occurrence of epilepsy have often been noted. However, the association between newly diagnosed epilepsy and psychiatric disorders afterward is not completely understood. We conducted two longitudinal cohorts for patients with and without epilepsy to investigate the risk factors and hazard ratios of developing psychiatric disorders after patients were newly diagnosed with epilepsy.

Methods

We identified 938 patients with a new diagnosis of epilepsy and 518,748 participants without epilepsy from the National Health Insurance Research Database in 2000–2002 and tracked them until 2008. We compared the incidence of developing psychiatric disorders between the two cohorts, evaluated risk factors and measured the associated hazard ratios (HRs) and 95% confidence intervals (CIs) of developing psychiatric disorders.

Findings

The incidences of psychiatric disorders for people with and without epilepsy were 94.1 and 22.6 per 1000 person-years, respectively. After adjusting the covariates, the epilepsy cohort showed the highest risks in mental retardation (HR 31.5, 95% CI 18.9 to 52.4), bipolar disorder (HR 23.5, 95% CI 11.4 to 48.3) and alcohol or drug psychosis (HR 18.8, 95% CI 11.1 to 31.8) among psychiatric complications developed after newly diagnosed epilepsy. The risk increased with epileptic general seizure and frequency of outpatient visits for epilepsy, as well as with emergency room visits and hospitalizations for epilepsy, and with older age. Chronologically, the highest risk occurred in the first year after epilepsy diagnosis (HR 11.4, 95% CI 9.88 to 13.2).

Conclusion

Various psychiatric disorders were demonstrated after newly diagnosed epilepsy and closely related to general seizure and use of medical services for epilepsy. This shows a need for integrated psychiatric care for patients newly diagnosed with epilepsy, especially in the first year.     

Clinical course of untreated tonic-clonic seizures in childhood: prospective,hospital based study.

OBJECTIVE: To assess decleration and acceleration in the disease process in the initial phase of epilepsy in children with new onset tonic-clonic seizures. STUDY DESIGN: Hospital based follow up study. SETTING: Two university hospitals, a general hospital, and a children''s hospital in the Netherlands. PATIENTS: 204 children aged 1 month to 16 years with idiopathic or remote symptomatic, newly diagnosed, tonic-clonic seizures, of whom 123 were enrolled at time of their first ever seizure; all children were followed until the start of drug treatment (78 children), the occurrence of the fourth untreated seizure (41 children), or the end of the follow up period of two years (85 untreated children). MAIN OUTCOME MEASURES: Analysis of disease pattern from first ever seizure. The pattern was categorised as decelerating if the child became free of seizures despite treatment being withheld. In cases with four seizures, the pattern was categorised as decelerating if successive intervals increased or as accelerating if intervals decreased. Patterns in the remaining children were classified as uncertain. RESULTS: A decelerating pattern was found in 83 of 85 children who became free of seizures without treatment. Three of the 41 children with four or more untreated seizures showed a decelerating pattern and eight an accelerating pattern. In 110 children the disease process could not be classified, mostly because drug treatment was started after the first, second, or third seizure. The proportion of children with a decelerating pattern (42%, 95% confidence interval 35% to 49%) may be a minimum estimate because of the large number of patients with an uncertain disease pattern. CONCLUSIONS: Though untreated epilepsy is commonly considered to be a progressive disorder with decreasing intervals between seizures, a large proportion of children with newly diagnosed, unprovoked tonic-clonic seizures have a decelerating disease process. The fear that tonic-clonic seizures commonly evolve into a progressive disease should not be used as an argument in favour of early drug treatment in children with epilepsy.     

Epileptic seizures in a heterogeneous excitatory network with short-term plasticity

Epilepsy involves a diverse group of abnormalities, including molecular and cellular disorders. These abnormalities prove to be associated with the changes in local excitability and synaptic dynamics. Correspondingly, the epileptic processes including onset, propagation and generalized seizure may be related with the alterations of excitability and synapse. In this paper, three regions, epileptogenic zone (EZ), propagation area and normal region, were defined and represented by neuronal population model with heterogeneous excitability, respectively. In order to describe the synaptic behavior that the strength was enhanced and maintained at a high level for a short term under a high frequency spike train, a novel activity-dependent short-term plasticity model was proposed. Bifurcation analysis showed that the presence of hyperexcitability could increase the seizure susceptibility of local area, leading to epileptic discharges first seen in the EZ. Meanwhile, recurrent epileptic activities might result in the transition of synaptic strength from weak state to high level, augmenting synaptic depolarizations in non-epileptic neurons as the experimental findings. Numerical simulation based on a full-connected weighted network could qualitatively demonstrate the epileptic process that the propagation area and normal region were successively recruited by the EZ. Furthermore, cross recurrence plot was used to explore the synchronization between neuronal populations, and the global synchronization index was introduced to measure the global synchronization. Results suggested that the synchronization between the EZ and other region was significantly enhanced with the occurrence of seizure. Interestingly, the desynchronization phenomenon was also observed during seizure initiation and propagation as reported before. Therefore, heterogeneous excitability and short-term plasticity are believed to play an important role in the epileptic process. This study may provide novel insights into the mechanism of epileptogenesis.     

Dynamic Imaging of Coherent Sources Reveals Different Network Connectivity Underlying the Generation and Perpetuation of Epileptic Seizures

The concept of focal epilepsies includes a seizure origin in brain regions with hyper synchronous activity (epileptogenic zone and seizure onset zone) and a complex epileptic network of different brain areas involved in the generation, propagation, and modulation of seizures. The purpose of this work was to study functional and effective connectivity between regions involved in networks of epileptic seizures. The beginning and middle part of focal seizures from ictal surface EEG data were analyzed using dynamic imaging of coherent sources (DICS), an inverse solution in the frequency domain which describes neuronal networks and coherences of oscillatory brain activities. The information flow (effective connectivity) between coherent sources was investigated using the renormalized partial directed coherence (RPDC) method. In 8/11 patients, the first and second source of epileptic activity as found by DICS were concordant with the operative resection site; these patients became seizure free after epilepsy surgery. In the remaining 3 patients, the results of DICS / RPDC calculations and the resection site were discordant; these patients had a poorer post-operative outcome. The first sources as found by DICS were located predominantly in cortical structures; subsequent sources included some subcortical structures: thalamus, Nucl. Subthalamicus and cerebellum. DICS seems to be a powerful tool to define the seizure onset zone and the epileptic networks involved. Seizure generation seems to be related to the propagation of epileptic activity from the primary source in the seizure onset zone, and maintenance of seizures is attributed to the perpetuation of epileptic activity between nodes in the epileptic network. Despite of these promising results, this proof of principle study needs further confirmation prior to the use of the described methods in the clinical praxis.     

Evaluation of the Anticonvulsant Effect of Brilliant Blue G,a Selective P2X7 Receptor Antagonist,in the <Emphasis Type="Italic">iv</Emphasis> PTZ-, Maximal Electroshock-, and 6 Hz-Induced Seizure Tests in Mice

Epilepsy is one of the most common neurological disorders which is diagnosed in around 65 million people worldwide. Clinically available antiepileptic drugs fail to control epileptic activity in about 30% of patients and they are merely symptomatic treatments and cannot cure or prevent epilepsy. There remains a need for searching new therapeutic strategies for epileptic disorders. The P2X7 receptor has been recently investigated as a new target in epilepsy treatment. Preclinical studies revealed that P2X7 receptor antagonists have anticonvulsant properties in some models of epilepsy. We aimed to investigate whether P2X7 receptor antagonist—brilliant blue G (BBG)—is able to change seizure threshold in three acute seizure models in mice, i.e., in the intravenous pentylenetetrazole seizure threshold, maximal electroshock seizure threshold and 6 Hz psychomotor seizure threshold tests. BBG was administered acutely (50–200 mg/kg, 30 min before the tests) and sub-chronically (25–100 mg/kg, once daily for seven consecutive days). Moreover, the chimney and grip strength tests were used to estimate the influence of BBG on the motor coordination and muscular strength in mice, respectively. Our results revealed only a week anticonvulsant potential of the studied P2X7 receptor antagonist because it showed anticonvulsant action only in the 6 Hz seizure test, both after acute and sub-chronic administration. BBG did not significantly influence seizure thresholds in the remaining tests. Motor coordination and muscular strength were not affected by the studied P2X7 receptor antagonist. In summary, BBG does not possess any remarkable anticonvulsant potential in acute seizure models in mice.     

Breast-conservation treatment for early invasive breast cancer: prognostic factors for survival after salvage treatment of local recurrence

The aim of the study was to investigate prognosis of patients who develop an isolated local recurrence (ILR) after conservative surgery (CS) for early-stage invasive breast cancer. Between 1983 and 1987, 415 patients with stage I-II breast cancer were treated with CS. Of these patients, 68 developed an ILR. The mean follow-up time after ILR was 167 months. Cox models taking potential prognostic factors into account were used to estimate the risk of death. On univariate analysis, age (< or =40 vs. >40 years) at first treatment, time to ILR (< or =24 vs. >24 months), type of recurrence (true vs. new primary tumor, NP), and extent of recurrence (operable vs. inoperable) were, but initial tumor stage (pT1 vs. pT2), initial lymph node stage (pN-negative vs. -positive), adjuvant radiotherapy (yes vs. no), type of salvage surgery (wide excision vs. mastectomy), and recurrent tumor grade (1-2 vs. 3) were not significant predictors of post-recurrence survival. On multivariate analysis only time to ILR proved independent predictor of survival (relative risk: 3.2; 95% confidence interval: 1.4-7.3; p = 0.0051), and the age of the patients showed borderline significance (p = 0.0659). The 15-year actuarial rate of cause-specific survival after ILR was 58% for all patients, 60% and 0% for patients with operable or inoperable recurrence, 30% and 71% for patients with age < or =40 or >40 years, 25% and 72% for patients with time to ILR < or =24 or >24 months, 54% and 88% for patients with true recurrence or NP, and 92% for patients with age >40 years with NP, respectively. The rate of second local recurrence after salvage mastectomy or repeated wide excision was 16% and 28%, respectively (p = 0.2265). As a conclusion, many patients with ILR have good prognosis, particularly those with operable recurrence with prolonged time to ILR, or with NP. Salvage mastectomy is not mandatory for all CS patients.     

Extended Anticoagulant and Aspirin Treatment for the Secondary Prevention of Thromboembolic Disease: A Systematic Review and Meta-Analysis

Background

Patients who have had an unprovoked deep venous thrombosis (DVT) or pulmonary embolus (PE) are at a high risk for recurrent venous thromboembolism (VTE). Extended “life-long” anticoagulation has been recommended in these patients. However, the risk benefit ratio of this approach is controversial and the role of the direct oral anticoagulants (DOACs) and aspirin is unclear. Furthermore, in some patients with a “weak provoking factor” there is clinical equipoise regarding continuation or cessation of anticoagulant therapy after treatment of the acute VTE event.

Objective

A systematic review and meta-analysis to determine the risks (major bleeding) and benefits (recurrent VTE and mortality) of extended anticoagulation with vitamin k antagonists (VKA), DOACs and aspirin in patients with an unprovoked VTE and in those patients with clinical equipoise regarding continuation or cessation of anticoagulant therapy. In addition, we sought to determine the risk of recurrent VTE events once extended anti-thrombotic therapy was discontinued.

Data Sources

MEDLINE, Cochrane Register of Controlled Trials, citation review of relevant primary and review articles.

Study Selection

Randomized placebo-controlled trials (RCTs) that compared the risk of recurrent VTE in patients with an unprovoked DVT or PE who had been treated for at least 3 months with a VKA or a DOAC and were then randomized to receive an oral anti-thrombotic agent or placebo for at least 6 additional months. We included studies that included patients in whom clinical equipoise existed regarding the continuation or cessation of anticoagulant therapy.

Data Extraction

Independent extraction of articles by both authors using predefined data fields, including study quality indicators. Data were abstracted on study size, study setting, initial event (DVT or PE), percentage of patients where the initial VTE event was unprovoked, the number of recurrent VTE events, major bleeds and mortality during the period of extended anticoagulation in the active treatment and placebo arms. In addition, we recorded the event rate once extended treatment was stopped. Meta-analytic techniques were used to summarize the data. Studies were grouped according to the type of anti-thrombotic agent.

Data Synthesis

Seven studies which enrolled 6778 patients met our inclusion criteria; two studies evaluated the extended use of Coumadin, three studies evaluated a DOAC and two studies evaluated the use of aspirin. The duration of followup varied from 6 to 37 months. In the Coumadin and aspirin studies 100% of the randomized patients had an unprovoked VTE, while in the DOAC studies between 73.5% and 93.2% of the VTE events were unprovoked. In the control group recurrent VTE occurred in 9.7% of patients compared to 2.8% in the active treatment group (OR 0.21; 95% CI 0.11–0.42, p<0.0001). VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with VKA and DOACs being significantly more effective than aspirin. Major bleeding events occurred in 12 patients in the control group (0.4%) and 25 of 3815 (0.6%) patients in the active treatment group (OR 1.64; 95% CI 0.69–3.90, NS). There were 39 (1.3%) deaths in control patients and 33 (0.9%) deaths in the anti-thrombotic group during the treatment period (OR 0.73; 95% CI 0.40–1.33, NS). Patients whose initial VTE event was a PE were more likely to have a recurrent PE than a DVT. The annualized event rate after discontinuation of extended antithrombotic therapy was 4.4% in the control group and 6.5% in the active treatment arm.

Conclusions

VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with DOACs and VKA being more effective than aspirin. The decision regarding life-long anticoagulation following an unprovoked DVT or PE should depend on the patients’ risk for recurrent PE as well as the patients’ values and preferences.     

The Impact of Short-Term,Intensive Antifolate Treatment (with Pyrimethamine and Sulfadoxine) and Antibiotics Followed by Long-Term,Secondary Antifolate Prophylaxis on the Rate of Toxoplasmic Retinochoroiditis Recurrence

PurposeTo assess the impact of intensive antifolate treatment, followed by secondary antifolate prophylaxis (A-SP) on the recurrence rate of toxoplasmic retinochoroiditis (TRC). To investigate whether there are any other factors potentially predisposing for recurrence.ResultsWhen secondary antifolate prophylaxis (A-SP) was instituted immediately after the treatment for TRC, the probability of 3-year recurrence–free survival after the first course of A-SP was 90.9%. A recurrence was most likely approximately 3.5 years after the first treatment. A univariate Cox regression model demonstrated that a risk for recurrence was 2.82 times higher (p = 0.02) in patients with retinal scars. In the multivariate analysis, the risk for recurrence was 2.41 higher (p = 0.06). In patients with haemorrhagic lesions the risk for recurrence was lower, aRR = 0.17 (approaching borderline statistical significance p = 0.08).ConclusionsWith the institution of A-SP of immediately after the intensive treatment for TRC, i.e. when a reactivation was most likely, there was no recurrence during A-SP. Following A-SP the recurrence rates were low and recurrence-free periods tended to be longer. The treatment regimen employed had a beneficial effect on the recurrence interval as it reduced and delayed the highest probability of recurrence.     

Ubiquitin Carboxy-Terminal Hydrolase L1 (UCH-L1) is increased in cerebrospinal fluid and plasma of patients after epileptic seizure

ABSTRACT: BACKGROUND: Clinical and experimental studies have demonstrated that seizures can cause molecular and cellular responses resulting in neuronal damage. At present, there are no valid tests for assessing organic damage to the brain associated with seizure. The aim of this study was to investigate cerebrospinal fluid (CSF) and plasma concentrations of Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), a sensitive indicator of acute injury to brain neurons, in patients with tonic--clonic or partial secondarily generalized seizures due to various etiologies. METHODS: CSF and plasma concentrations of UCH-L1 were assessed in 52 patients within 48 hours after epileptic seizure and in 19 controls using ELISA assays. RESULTS: CSF obtained within 48 hours after seizure or status epilepticus (SE) presented significantly higher levels of UCH-L1 compared to controls (p = 0.008). Plasma UCH-L1 concentrations were negatively correlated with time to sample withdrawal. An analysis conducted using only the first 12 hours post-seizure revealed significant differences between concentrations of UCH-L1 in plasma and controls (p = 0.025). CSF and plasma concentrations were strongly correlated with age in patients with seizure, but not in control patients. Plasma UCH-L1 levels were also significantly higher in patients after recurrent seizures (n = 4) than in those after one or two seizures (p = 0.013 and p = 0.024, respectively). CONCLUSION: Our results suggest that determining levels of neuronal proteins may provide valuable information on the assessment of brain damage following seizure. These data might allow clinicians to make more accurate therapeutic decisions, to identify patients at risk of progression and, ultimately, to provide new opportunities for monitoring therapy and targeted therapeutic interventions.