Treatment Strategies for Myoclonic Seizures and Epilepsy Syndromes with Myoclonic Seizures

Summary:   Despite the availability of numerous treatment options, the diagnosis and treatment of myoclonic seizures continue to be challenging. Based on clinical experience, valproate and benzodiazepines have historically been used to treat myoclonic seizures. However, many more treatment options exist today, and the clinician must match the appropriate treatment with the patient's epilepsy syndrome and its underlying etiology. Comorbidities and other medications must also be considered when making decisions regarding treatment. Rarely, some antiepileptic drugs may exacerbate myoclonic seizures. Most epileptic myoclonus can be treated pharmacologically, but some cases respond better to surgery, the ketogenic diet, or vagus nerve stimulation. Because myoclonic seizures can be difficult to treat, clinicians should be flexible in their approach and tailor therapy to each patient.     

蛛网膜下腔出血患者预后临床多因素分析

目的 分析蛛网膜下腔出血（subarachnoid hemorrhage,SAH）患者临床预后的影响因素。方法 分析2007～2008年我院神经内科收治的蛛网膜下腔出血且住院期间完成数字减影血管造影（digital subtraction angiography,DSA）检查的患者共136例,分别收集患者自然信息、病前合并疾病、Hunt-Hess、Fisher分级、全脑血管造影结果、发病时格拉斯哥昏迷评分（Glasgow coma scale,GCS）、并发症及出院时改良的Ranking量表评分（modified Ranking Scale,mRS）等情况,进行单因素和多因素回归分析。结果 血管痉挛、再出血、感染、发热、Hunt-Hess评分、CT Fisher分级、GCS 评分、DSA结果等因素具有统计学意义（P＜0.05）。结论 动脉瘤性蛛网膜下腔出血患者,高Hunt-Hess及CT Fisher分级、GCS评分差,或合并感染、发热、血管痉挛、再出血的患者预后差。     

Seizures after Spontaneous Intracerebral Hemorrhage

Objective

In patients with spontaneous intracerebral hemorrhage (ICH), the risk factors for seizure and the effect of prophylactic anticonvulsants are not well known. This study aimed to determine the risk factor for seizures and the role for prophylactic anticonvulsants after spontaneous ICH.

Methods

Between 2005 and 2010, 263 consecutive patients with spontaneous ICH were retrospectively assessed with a mean follow-up of 19.5 months using medical records, updated clinical information and, when necessary, direct patient contact. The seizures were classified as early (within 1 week of ICH) or late (more than 1 week after ICH). The outcomes were measured with the Glasgow Outcome Scale at discharge and the modified Rankin Scale (mRS) at both 2 weeks and discharge.

Results

Twenty-two patients (8.4%; 9 patients with early seizures and 13 patients with late seizures) developed seizures after spontaneous ICH. Out of 263 patients, prophylactic anticonvulsants were administered in 216 patients. The prophylactic anticonvulsants were not associated with a reduced risk of early (p=0.094) or late seizures (p=0.326). Instead, the factors associated with early seizure were cortical involvement (p<0.001) and younger age (60 years or less) (p=0.046). The risk of late seizure was increased by cortical involvement (p<0.001) and communicating hydrocephalus (p=0.004). The prophylactic anticonvulsants were associated with a worse mRS at 2 weeks (p=0.024) and at last follow-up (p=0.034).

Conclusion

Cortical involvement may be a factor for provoked seizures. Although the incidence of early seizures tended to decrease in patients prescribed prophylactic anticonvulsants, no statistical difference was found.     

Alcohol, Seizures, and Epilepsy

Summary: Seizures, epilepsy, and alcohol are complexly interrelated. Although it is commonly perceived that patients with epilepsy experience problems with seizure control if they use alcohol, this is not confirmed by the few experimental studies that have tested the hypothesis. The last 30 years have emphasized the role of withdrawal from alcohol as a mechanism of seizure production. However, this is but one of many potential mechanisms by which seizures and epilepsy may be related to alcohol use and abuse. The rare but clear situations in which alcohol can act as a convulsant drug need further study, and mechanisms by which the long-term neurotoxic effects of alcohol lead to chronic epilepsy also need further elucidation.     

蛛网膜下腔出血继发症状性癫痫的发生率、危险因素及院内结局：来自中国卒中联盟登记数据库的分析

目的调查蛛网膜下腔出血(subarachnoid hemorrhage,SAH)患者继发症状性癫痫的发生率、相关危险因素及其与院内结局的关系。方法本研究数据来源于中国卒中联盟(China Stoke Center Alliance,CSCA)登记数据库2015年8月1日-2019年7月31日入组的SAH患者。症状性癫痫限定为住院期间发作。依据是否出现继发症状性癫痫,将研究对象分为SAH继发癫痫组和无继发癫痫组,比较组间的人口学特征、入院GCS评分、血管危险因素、手术以及医院级别和地区的差异。采用多因素Logistic回归,分析SAH继发癫痫的危险因素,以及SAH继发癫痫与院内死亡、缺血性卒中、脑出血及肺炎的相关性。结果本研究纳入11 210例SAH患者,女性6623例(59.1%),平均年龄60.0±12.9岁,入院GCS评分的中位数为15分。总计228例(2.0%)继发症状性癫痫。年龄(OR 0.92,95%CI 0.87～0.97)、既往卒中/TIA(OR 1.61,95%CI 1.20～2.17)、颈动脉狭窄(OR 3.17,95%CI 1.27～10.85)、心房颤动(OR 2.64,95%CI 1.12～6.24)、脂代谢紊乱(OR 1.79,95%CI 1.03～3.13)和脑室外分流术(OR 2.30,95%CI 1.31～4.02)是SAH继发症状性癫痫的独立影响因素。SAH继发症状性癫痫可能与更高的院内死亡(OR 1.71,95%CI 0.96～3.05)、缺血性卒中(OR 4.21,95%CI 2.70～6.56)、脑出血(OR 3.87,95%CI 2.81～5.33)及肺炎(OR 2.96,95%CI 2.26～3.86)事件风险相关。结论症状性癫痫是SAH患者较为常见的神经系统并发症,低龄、既往卒中/TIA、颈动脉狭窄、心房颤动、脂代谢紊乱以及脑室外分流术是SAH继发症状性癫痫的独立危险因素。SAH继发症状性癫痫增加院内死亡、缺血性卒中、脑出血以及肺炎的风险。     

Sudden Unexpected Death in Epilepsy: A Review of Incidence and Risk Factors

Summary:  Sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. However, SUDEP is rare in patients with new onset epilepsy and in patients in remission. Incidence is about 0.35 cases/1,000 person-years in population-based incidence cohort of epilepsy. Incidence is considerably higher in patients with chronic epilepsy, 1–2/1,000 person-years, and highest with severe, refractory seizures, 3–9/1,000. The highest rates occur from 20 to 40 years. Most SUDEP appears seizure-related. When witnessed, the fatal event generally occurred in association with generalized tonic–clonic seizure. Two recent case–control studies suggest that seizure frequency is the strongest risk factor for SUDEP: relative risk = 23 (95% CI = 3.2–170) for persons with ≥1 seizure during the year of observation versus seizure-free patients. Onset of epilepsy at an early age and long duration of the disorder are other risk factors. Although SUDEP has not been associated with the use of any particular antiepileptic drugs (AEDs), some case–control studies have pointed to an association between SUDEP and polytherapy with AEDs and frequent dose changes independent of seizure frequency. Although recent epidemiological studies have been helpful in identifying patients at risk for SUDEP, providing clues to mechanisms behind SUDEP, no single risk factor is common to all SUDEP, suggesting multiple mechanisms or trigger factors. Seizure control seems of paramount importance to prevent SUDEP. Further large-scale case–control studies are needed to assess the role of AEDs in order to form a basis for treatment strategies aiming at seizure control and prevention of SUDEP.     

Risk Factors for Sudden Unexpected Death in Epilepsy

Summary: The exact mechanisms of sudden unexpected death in individuals with epilepsy (SUDEP) are unclear, and only an incomplete analysis of risk factors can be made. Clinical, epidemiologic, and electrophysiologic evidence suggests that most sudden deaths are related temporally to seizures, are unwitnessed, and that many occur during sleep. Individuals with generalized seizures, symptomatic epilepsy, severe or frequent seizures, and additional mental handicap or neurologic deficit are at greater risk, and the majority of cases probably occur in patients with chronic epilepsy. Young people are more at risk for SUDEP than older people with epilepsy, and risk factors in pediatric practice may differ from those in adult epileptology.     

蛛网膜下腔出血患者继发症状性脑血管痉挛的相关危险因素分析

目的 研究探讨动脉瘤性蛛网膜下腔出血（subarachnoid hemorrhage,SAH）继发症状性脑血管痉挛 （symptomatic cerebral vasospasm,SCVS）的相关危险因素,为SCVS的防治提供参考。 方法 回顾性分析96例SAH患者临床资料,对性别、年龄、高血压史、糖尿病史、Fisher分级等影响因 素进行统计学分析。 结果 96例患者中发生SCVS的患者共39例,单因素分析结果显示SCVS组与非SCVS组在年龄、高血 压、吸烟、脑室内积血、Hunt-Hess分级、Fisher分级、数字减影血管造影（digital subtraction angiography, DSA）显示血管痉挛程度、尼莫地平使用等方面差异有显著性;多因素Logistic回归分析结果显示：低 龄、高血压史、Fisher分级是发生SCVS的危险因素,其比值比（odds ratio,OR）分别为0.567、1.982和 2.713;而尼莫地平的使用是SCVS发生的保护因素,OR为0.799。 结论 SAH后SCVS是多种因素共同作用的结果,其中低年龄、高血压史、Fisher分级是SCVS的独立危 险因素,尼莫地平使用为保护因素。     

急性期胰岛素样生长因子-1对动脉瘤性蛛网膜下腔出血院内并发症及短期预后的预测作用

目的 探讨胰岛素样生长因子-1（insulin like growth factor-1,IGF-1）水平对动脉瘤性蛛网膜下腔出 血（aneurysmal subarachnoid hemorrhage,aSAH）患者院内并发症及出院时临床预后的预测价值。 方法 连续入组发病72 h内的aSAH患者及健康对照。在动脉瘤闭塞术前采集血样,测定血浆IGF-1水 平。对患者基本信息,神经内分泌因子、院内并发症及结局进行分析,用Logistic回归确定院内并发症 及出院时预后不良（mRS评分＞2分）的预测因素,计算预测因素的受试者工作特征曲线下面积。 结果 共入组118例aSAH患者和122例健康对照者。aSAH患者血浆IGF-1水平较健康对照低[69.00 （50.98,93.85）ng/mL vs 81.05（69.40,102.78）ng/mL,P <0.0001]。37例（31.4%）患者出院时预 后不良。IGF-1浓度越低（OR 0.971,95%CI 0.946～0.996,P =0.0262）、入院时Hunt-Hess分级3～5 级（OR 4.995,95%CI 1.331～18.747,P =0.0007）、住院期间发生迟发型脑缺血（OR 46.100,95%CI 11.152～190.566,P <0.0001）及脑积水（OR 7.768,95%CI 1.088～55.463,P =0.0284）的患者预后不良 风险增高。IGF-1与Hunt-Hess分级、迟发型脑缺血的预测价值基本相同（P >0.05）。71例（60.2%）患者 住院期间发生至少1种并发症。仅有入院时I GF-1浓度（OR 0.984,95%CI 0.973～0.996,P =0.0082）对 院内并发症有预测价值。 结论 aSAH急性期患者血浆IGF-1浓度越低,住院期间并发症发生率越高,出院时功能预后越差。     

Aneurysmal Subarachnoid Hemorrhage in Third and Fourth Decades of Life

Objective

The aim of this study was to compare clinical characteristics of ruptured aneurysms in young adults, of the third and fourth decades of life, and to compare several clinical characteristics affecting the outcome of patients.

Methods

We retrospectively investigated 1459 patients who underwent surgery and endovascular treatment for ruptured cerebral aneurysms from June 1992 to December 2010 and compared clinical characteristics. We also reviewed pre-existing medical conditions and perioperative complications.

Results

Among 1459 patients, there were 21 patients (1.44%) in the third decade and 104 patients (7.13%) in the fourth decade of life. Within two age groups, 88 (70.4%) were male and 37 (29.6%) were female, a ratio of 2.37 : 1. In both groups, we observed the anterior cerebral artery (ACA) aneurysm with the most frequency (p=0.028). In general, favorable outcome was achieved in both age groups (90.5% and 81.7%, respectively). An initial univariate analysis showed Hunt-Hess grade, Fisher grade, location of aneurysm, and rebleeding significantly associated with outcome after aneurysm rupture. Further, multivariate analysis demonstrated that only Hunt-Hess grade (grade 4-5) was a risk factor for the outcome (odds ratio=9.730, 95% confidence interval 2.069-45.756, p=0.004).

Conclusion

The incidence of subarachnoid hemorrhage (SAH) was higher in the male population of the third and fourth decades of life. Aneurysms on the ACA were most frequently occurred in both age groups and the outcome of aneurysmal SAH among the third and fourth decades was favorable. Multivariate analysis revealed that high Hunt-Hess grade was a risk factor for patient''s outcome.     

Incidence of Epilepsy and Unprovoked Seizures in Rochester, Minnesota: 1935–1984

Summary: The incidence of epilepsy and of all unprovoked seizures was determined for residents of Rochester, Minnesota U.S.A. from 1935 through 1984. Ageadjusted incidence of epilepsy was 44 per 100,000 personyears. Incidence in males was significantly higher than in females and was high in the first year of life but highest in persons aged ≥75years. Sixty percent of new cases had epilepsy manifested by partial seizures, and two thirds had no clearly identified antecedent. Cerebrovascular disease was the most commonly identified antecedent, accounting for 11% of cases. Neurologic deficits from birth, mental retardation and/or cerebral palsy, observed in 8% of cases, was the next most frequently identified preexisting condition. The cumulative incidence of epilepsy through age 74 years was 3.1%. The age-adjusted incidence of all unprovoked seizures was 61 per 100,000 person-years. Age-and gender-specific incidence trends were similar to those of epilepsy, but a higher proportion of cases was of unknown etiology and was characterized by generalized onset seizures. The cumulative incidence of all unprovoked seizures was 4.1% through age 74 years. With time, the incidence of epilepsy and of unprovoked seizures decreased in children and increased in the elderly.     

Continual Transcranial Doppler in the Monitoring of Hemodynamic Change following Aneurysmal Subarachnoid Hemorrhage

Aims: To analyze and compare the value of different treatment methods for acute aneurysmal subarachnoid hemorrhage (aSAH)‐related vasospasm. Cerebral hemodynamic variables’ changes were evaluated by transcranial Doppler (TCD) in aSAH patients within 14 days after onset. Methods: Thirty aSAH patients were enrolled in the study within 72 h after onset. Baseline CT and TCD were used for assessment. Patients were divided into three groups according to SAH severity and patients’ discretion: nonsurgical group, endovascular coiling, and neurosurgical clipping. TCD hemodynamic parameters were measured and Lindegaard index was calculated daily from onset to 14th day after SAH. The group mean cerebral blood velocity (MBFV) and Lindegaard index were compared using repeated measures analysis of variance (reANOVA). Least Significant Difference (LSD) test was used for post hoc comparison. All 30 patients were followed for 90 days after onset for outcome assessment. Results: The values of MBFV and Lindegaard index of anterior cerebral artery (ACA)/middle cerebral artery (MCA) from high to low is nonsurgical group, clipping and coiling (ACA: P= 0.0001/P= 0.006; MCA: P= 0.243/P= 0.317). Conclusions: These results indicate that both neurosurgical clipping and endovascular coiling management may relieve the severity of cerebral vasospasm in acute aSAH.     

Seizure Frequency and Duration of Epilepsy are Not Risk Factors for Postoperative Seizure Outcome in Patients with Hippocampal Sclerosis

PURPOSE: Despite accurate localization of the seizure focus, not all patients are seizure free after temporal lobectomy. This study determined risk factors for seizure recurrence in patients with proven hippocampal sclerosis. METHODS: The outcome from surgery was assessed in 56 consecutive patients with proven hippocampal sclerosis. The age at surgery, duration of epilepsy, history and age of febrile seizures, age of onset of epilepsy, sex ratio, laterality of seizure focus, and seizure frequency were compared between patients seizure free and those not seizure free, and those seizure and aura free and those with seizure recurrence including auras. RESULTS: During a mean follow-up of 38 months, 48 (86%) of 56 are seizure free. The mean age at surgery (37 vs. 36 years), duration of epilepsy (26 vs. 22 years), age (1.6 vs. 1.1 years), and occurrence (58 vs. 75%) of febrile seizures, age of onset of epilepsy (11 vs. 14 years), sex ratio (50 vs. 75% female), laterality of seizure focus (42 vs. 50% left), greater than weekly seizures (40 vs. 38%), and a history of (69 vs. 75%) and frequency of (2.10 vs. 2.38 per year) secondarily generalized seizures did not differ significantly between the two groups. Similarly there was no significant difference between patients seizure and aura free and those with seizure recurrence including auras. CONCLUSIONS: Clinical factors such as seizure frequency and duration of epilepsy are not risk factors for postoperative seizure recurrence.     

AE Mice: An Inbred Mouse Strain with Interesting Features for Epilepsy Research

Spontaneous clonic-tonic seizures were occasionally observed in inbred AE mice of both sexes. Determination of seizure thresholds in this strain showed that both female and male AE mice had electroconvulsive thresholds that were markedly lower than those of other strains of mice, whereas susceptibility to seizures induced by pentylenetetrazol was not increased. The antiepileptic drug phenobarbital was much less effective in blocking electroconvulsions in AE mice than in other strains. Similarly, valproic acid was less effective in protecting against pentylenetetrazol-induced seizures. These differences in anticonvulsant efficacy could be explained only partly by differences in pharmacokinetics, thus indicating a lower responsiveness of AE mice to antiepileptic drugs. Determination of the GABA-synthesizing enzyme glutamic decarboxylase in different brain regions showed no significant difference between AE mice and normal NMRI mice except for a lower GAD activity in corpus striatum of male AE mice. The data indicate that AE mice may be an interesting new genetic model of epilepsy.     

Rolandic Epilepsy: An Incidence Study in Iceland

Summary: Purpose: We wished to determine incidence, clinical features, and prognosis of benign rolandic seizures (BRS) and benign rolandic epilepsy (BRE) in a total population.
Methods: Cases were ascertained through review of all EEG records, and diagnosis was verified by review of medical records. Follow-up information regarding seizures and treatment was obtained from parents and treating physicians.
Results: In the Icelandic population aged 3–15 years, the incidence of BRS is 6.2 and BRE 4.7 in 100,000. Five years after onset 95% were seizure-free. At last follow-up, all were seizure free and had not been treated with antiepileptic drugs (AEDs) for at least 1 year.
Conclusions: Our study demonstrates that BRS is a common entity in children. The prognosis is excellent and treatment is not necessary in all cases. It is important to identify BREBRS correctly and distinguish it from other types of epilepsy.     

蛛网膜下腔出血相关性肺炎发生的危险因素分析及对住院结局的影响

目的 分析蛛网膜下腔出血（subarachnoid hemorrhage,SAH）相关性肺炎发生的危险因素及其对住院 结局的影响。 方法 回顾性纳入2015年5月-2018年11月首都医科大学附属北京天坛医院收治的SAH患者,根据住 院期间是否发生肺炎分为肺炎组、非肺炎组,比较两组患者临床资料的差异。采用多因素Logistic回归 模型,分析发生肺炎的危险因素,以及发生肺炎对SAH患者院内死亡、住院天数、住院总费用的影响。 结果 共纳入457例SAH患者,平均年龄54.3±11.2岁,男性219例（47.9%）,发生肺炎76例（16.6%）。 男性（OR 2.31,95%CI 1.17～4.58,P =0.016）、吞咽障碍（OR 6.06,95%CI 1.09～33.70,P =0.039）及 Barthel指数0～20分（OR 15.58,95%CI 4.17～58.23,P＜0.001）是SAH患者发生肺炎的独立危险因素; 发生肺炎与院内死亡风险、住院天数和住院总费用增加无关。 结论 男性、吞咽障碍、Barthel指数0～20分是SAH患者发生肺炎的独立危险因素。发生肺炎与院内 死亡风险、住院天数和住院总费用增加无关。