From gene to disease; progressive myoclonus epilepsy of Unverricht-Lundborg and mutations in the cystatin B gene

Progressive myoclonus epilepsy type 1 of Unverricht-Lundborg (EPM1) is a rare disorder, associated with mutations in the cystatin B (CSTB) gene. The most prevalent molecular abnormality is an expansion of a dodecamer repeat in the promoter region of the CSTB gene, but point mutations in the CSTB gene have also been found. DNA examination may be useful in discriminating EPM1 from juvenile myoclonic epilepsy, and from other types of progressive myoclonus epilepsy. An early diagnosis is important to optimise treatment and to provide an adequate prognosis and prediction of recurrence.     

Surgically treatable epilepsy--a review

20-25% of epileptic patients do not become seizure free on adequate drug therapy. In 25-50% of patients with intractable epilepsy, the brain area responsible for seizures is well localizable and does not involve eloquent regions. In these patients, the surgical excision of the epileptic focus may lead to relief from seizures. In Hungary, there may be 5-6000 patients who needs an epilepsy surgery, but till now only 200 patients with chronic epilepsy underwent a surgical procedure. In the surgically remediable epilepsies, the operation is not a "ultima ratio". Concerning these syndromes, if 2-3 adequate antiepileptic drugs do not lead to seizure freedom within 1-3 years after the epilepsy onset, then a presurgical evaluation is necessary. The most common surgically remediable epilepsy is the temporal lobe epilepsy in which 60-90% of drug-resistant patients could be surgically cured. In lesional neocortical epilepsies 50-80% of patients become postoperatively seizure free. In childhood hemispheric epilepsies, the surgery could lead to seizure freedom in 70-80% of patients. The basic tools of the presurgical evaluation are the detailed history, the high resolution-MRI, the video-EEG monitoring, and the neuropsychological assessment. These investigation methods are usually enough to evaluate the necessity of the surgery and the postoperative outcome as well as to plan the localization and the extension of the resection. In some cases, ictal SPECT, PET, or video-EEG monitoring with intracranial electrodes could also be necessary in order to localize the epileptic focus.     

Organizing health care for people with seizures and epilepsy

The day-to-day responsibilities of managing seizures and epilepsy fall most heavily on patients and their families. Unfortunately, health care services in the United States are not organized to identify, diagnose, and treat people with seizures effectively nor are they delivered in such a way that patients and their families can engage in a positive, collaborative relationship with health care providers. This article describes a model of chronic illness care as applied to seizures and epilepsy, that is, how care should be structured to help people with seizures live as well as possible.     

Myoclonic epilepsy--pitfalls in diagnosis and management

Three cases of myoclonic epilepsy presenting in adolescence are described. Seizures were uninfluenced by treatment with carbamazepine. Substitution of sodium valproate in early adult life resulted in all becoming seizure-free. A high degree of clinical awareness is required in making the correct diagnosis and in choosing appropriate therapy for this form of epilepsy which can present with generalised tonic-clonic or partial seizures.     

小儿脑性瘫痪癫痫风险因素分析

目的 探讨小儿脑性瘫痪合并癫痫的临床特点及危险因素,为有效治疗提供参考依据。 方法 对522例脑性瘫痪患儿(合并癫痫92例,无合并癫痫430例)的高危因素、影像学资料等进行回顾性分析,并对合并癫痫的92例从临床发作特点、瘫痪类型及智力发育水平进行分析。 结果 522例脑瘫患儿合并癫痫的发生率是17.6%。低出生体重、颅内出血可作为小儿脑性瘫痪合并癫痫的危险因素(χ²=6.564和11.797,P均<0.05),而早产、窒息、黄疸两组间比较无统计学意义(P>0.05)。在影像学检查结果中,脑软化灶及脑结构畸形为癫痫的预测风险因子(χ²=5.250和14.020,P均<0.05),而脑发育不良、脑室扩大两组间比较差异无统计学意义(P>0.05)。癫痫的发作类型以强直阵挛发作最常见(44.5%),肌阵挛发作(28.3%)居第二位。97.7%的脑瘫合并癫痫患儿有不同程度的智力低下,四肢瘫患儿癫痫发病率最高(61.9%)。 结论 出生低体重、颅内出血患儿,以及四肢瘫合并智力发育落后、脑结构异常者发生癫痫的风险增高,临床应给予重视。     

The neurosurgical treatment of epilepsy

Despite the new advancements in antiepileptic drug development, thousands of people with epilepsy will remain intractable to medication. For a considerable proportion of these people, epilepsy surgery is a consideration for better control of their seizures. Resective surgery is now standard practice for patients with medication-refractory epilepsy. Temporal lobectomy continues to be the most common surgery performed. Once patients fail 2 to 3 optimal trials of antiepileptic medication, further drug therapy offers a minimal number of patients freedom from seizures. In contrast, temporal lobectomy in carefully selected patients may result in seizure-free outcomes in more than 70% to 90% of patients with intractable seizures. As technology and drug availability increases in the new millennium, it is important for the primary care physician to be aware of epilepsy surgery as a means to treat patients with antiepileptic drug-refractory epilepsy. Arch Fam Med. 2000;9:1142-1147     

Rhythmic EMG and EEG activity during voluntary movement in posthypoxic cortical action myoclonus

A patient with posthypoxic cortical action myoclonus was studied using polygraphic EEG-EMG recording techniques and transcranial magnetic stimulation. The myoclonic jerks were not stimulus-sensitive, and were not associated with enhancement of the somatosensory evoked potential (SEP). The most prominent electrophysiological finding was that rhythmic EMG activity was produced when the patient attempted rapid voluntary movement. EEG-EMG polygraph indicated that the rhythmic EMG activity was preceded by rhythmic activity in the EEG recorded overlying the contralateral central region. The frequency of both EEG and EMG activity was the same (approximately 50 Hz). Treatment using a combination of clonazepam, carbamazepine and primidone diminished the action myoclonus, concomitant with the disappearance of the rhythmic EEG and EMG activity. In the sensorimotor cortex of the normal monkey and humans, oscillatory activity ranging between 20-50 Hz has been recorded in the local field potential. Our findings suggest that cortical hyperoscillation may produce this characteristic rhythmic EEG and EMG activity and may, in turn, be related to cortical action myoclonus.     

Febrile seizures and epilepsy: the contributions of epidemiology

In the past, febrile seizures were considered to be a sign of epilepsy, a disorder characterised by recurrent unprovoked seizures. Currently, febrile seizures are considered to be a benign seizure syndrome that is distinct from epilepsy. This distinction has been possible largely because of the epidemiological evidence which is presented here in the form of a two-part argument. If febrile seizures are epilepsy one might expect that: (1) following a first febrile seizure, the risk of a second febrile seizure should be similar to the risk of an unprovoked seizure (in fact, the risk of a recurrent febrile seizure is approximately 34%, whereas the risk of an unprovoked seizure after having had a febrile seizure is approximately 2% to 3%); (2) the factors that predict recurrent febrile seizures should also predict subsequent unprovoked seizures. From the available literature, young age at the time of the first febrile seizure and a family history of febrile seizures predict recurrent febrile seizures, but do not predict subsequent unprovoked seizures. By contrast, a family history of epilepsy, complex febrile seizures and neurological abnormality are associated with an increased risk of subsequent epilepsy but are not consistently associated with the risk of a recurrent febrile seizure.     

癫痫和癫痫综合征的ICD-10编码

目的 为了满足医疗、教学、科研的需要,在实际工作中更方便准确地对各种癫痫和癫痫综合征分类编码.方法 收集临床上各种癫痫和癫痫综合征,根据ICD-10对癫痫和癫痫综合征的分类原则分别归类.结果 局部相关性（局灶性）（部分）特发性癫痫和癫痫综合征伴有局限性发作编码到G40.0;局部相关性（局灶性）（部分）症状性癫痫和癫痫综合征伴有单纯性部分性发作、不伴有意识改变,编码到G40.1;局部相关性（局灶性）（部分）症状性癫痫和癫痫综合征伴有复合性部分性发作、伴有意识改变、伴有记忆和形成概念的障碍,编码到G40.2;全身性特发性癫痫和癫痫综合征,编码到G40.3;其它全身性癫痫和癫痫综合征,编码到G40.4;特指的癫痫综合征,编码到G40.5;未特指的癫痫大发作（伴有或不伴有小发作）,编码到G40.6;未特指的癫痫小发作,不伴有大发作,编码到G40 7;其它癫痫NEC,编码到G40.8;未特指的癫痫,编码到G40.9.癫痫类疾病名称远超出了ICD-10第三卷癫痫索引条目,其中有21种癫痫和癫痫综合征未列入索引和国际疾病分类（ ICD-10） 应用指导手册,且多处同一分类亚目下出现多达10～20种癫痫和癫痫综合征.结论 有必要通过扩充适合我国国情的ICD-10字典库和采用扩展码的方法补充癫痫分类,以适用我国癫痫防治和管理的规范化,有利于我国癫痫的相关研究以及与国际接轨.     

影响脑性瘫痪患儿合并癫痫的危险因素分析

目的 分析影响脑性瘫痪(CP)患儿合并癫痫的危险因素,为防治CP患儿癫痫的发作提供参考。方法 回顾性分析2008年5月-2015年1月我院477例CP患儿的临床资料,按照患儿入院时有无癫痫发作分为癫痫发作组(病例组)和无癫痫发作组(对照组),对两组患儿的一般临床资料及影像学资料等进行比较,并对脑性瘫痪患儿继发癫痫的相关因素进行二分类非条件Logistic回归分析。结果 纳入的477例CP患儿中有86例合并癫痫(18.0%),癫痫患儿以四肢瘫最多见(61.6%),强直阵挛性发作是癫痫发作的主要类型(44.2%);多因素Logistic回归分析提示低出生体重(OR=2.793,P＜0.05)、脑软化(OR=3.185,P＜0.05)、颅内出血(OR=3.581,P＜0.05)、脑结构畸形(OR=5.839,P＜0.05)是CP患儿合并癫痫的独立危险因素。结论 CP患儿中具有脑软化、颅内出血、低出生体重及脑结构畸形的发生癫痫的风险显著增高,应当给予临床重视。     

儿童孤独症谱系障碍共患癫痫的诊治及管理

虽然儿童孤独症谱系障碍(ASD)共患癫痫现象已被识别多年,但二者之间的相互联系的确切机制尚不清楚。癫痫对ASD儿童精神行为影响研究尚少,但有较多的发育、社交沟通及自我照顾能力困难的倾向。需行治疗前综合性评估,包括病因学调查,及认知、语言、情感、社交及行为功能等评估。主要基于心理社会干预结合药物治疗。根据癫痫类型和药物耐受性,兼顾药物行为学副作用选择抗癫痫药。ASD患儿类似癫痫样发作行为常见,需仔细鉴别。疑似癫痫发作,应及时诊疗或转介。有证据显示ASD共患癫痫的难治性和死亡率增加。加强多学科交流是提高ASD共患癫痫早期识别及长程管理的重要环节。     

Management of Acute Repetitive Seizures

Acute repetitive seizures, more commonly known as cluster, crescendo or sequential seizures, are defined as episodes of increased seizure activity occurring in patients with refractory epilepsy who are already receiving stable regimens of anticonvulsants. They lie in the seizure spectrum between isolated seizures and status epilepticus. If acute repetitive seizures are left untreated, they may progress to status epilepticus.Acute repetitive seizures and prolonged seizures are rated as a neurological emergency and treatment must be prompt. The primary goals of therapy are cessation of the seizure and prevention of recurrence. The use of traditional intravenous agents such as phenytoin, phenobarbital (phenobarbitone), lorazepam and diazepam is well established in the first-line treatment of acute seizures. However, adverse effects and the time to onset of effect often dictate the choice between older anticonvulsants. Newer agents (such as fosphenytoin) and alternative routes of administration (such as rectal administration of diazepam solution) have been developed in an effort to reduce adverse effects, decrease the time to onset of effect, reduce acute care facility costs and investigate the possibility of home treatment.Diazepam rectal gel, a newer formulation of diazepam intended for rectal administration, effectively terminates acute seizures and prevents recurrence within the first 12 hours after administration. Diazepam rectal gel is available for use by a trained caregiver in a home setting and, therefore, emergency room treatment and hospitalisation may not be required and could be avoided. This may result in reductions in financial and emotional costs associated with acute repetitive seizures, but broader clinical experience is needed to assess this. Diazepam rectal gel is not associated with respiratory depression and most adverse effects appear to be mild to moderate in severity.At present, diazepam rectal gel is a valuable addition to the current anticonvulsant armamentarium for first-line therapy of acute repetitive seizures. Wider clinical experience will better determine the place of this formulation in the treatment of this debilitating disorder.     

Epilepsy in adolescents: diagnosis and treatment

Although seizures are one of the most common presenting neurologic problems in adolescence, the diagnosis and management of seizures in this population can be a challenge. Seizures can be secondary to an underlying illness or to a genetically based epileptic syndrome. The first task of the clinician is proper diagnosis and evaluation. The second task is to determine whether treatment with antiepileptic drugs (AEDs) is necessary and, if so, which AED is the most appropriate for the patient's epilepsy with the least impact on the adolescent's quality of life. The newer AEDs allow the clinician more flexibility to treat not only the epilepsy, but also any coexisting medical conditions in the patient. The impact of epilepsy on the quality of life of the adolescent cannot be overestimated. Epilepsy affects the adolescent's social life, peer interactions, educational and career decisions, driving ability, and reproductive life. Communication with the adolescent regarding the effect epilepsy can have on these issues is crucial to proper management of the patient. Although treating the seizures and all of the ramifications of the diagnosis is a challenge, the majority of adolescents can achieve the primary goals of therapy: seizure freedom and the maintenance of high quality of life.     

Role of epileptogenic lesions in the development of ictal and interictal epileptic disturbance

The most common cause of focal epilepsies is the morphological brain abnormality, the epileptogenic lesion. Nowadays, by using MRI, the epileptogenic lesion can be demonstrated in vivo in more and more cases. Our knowledge regarding the clinical and pathophysiological features of epilepsy should be reevaluated in the highlight of the epileptogenic lesions demonstrated by MRI. The presence and the type of the epileptogenic lesion are important prognostic factors in the pharmacological and surgical treatments of epilepsy. Because the localization of the lesion is usually identical with the site of the seizure onset, the MRI investigation play an important role not only in identifying the epilepsy etiology but also in the non-invasive localization of the epileptic focus. Tumors, malformations of the cortical development, the hippocampal sclerosis, perinatal lesions, posttraumatic scars and the vascular malformations are the most important morphological abnormalities associated with epilepsy. Low-grade astrocytoma, pilocytic astrocytoma, oligodendroglioma, ganglioglioma, and the dysembrioplastic neuroepithelial tumors are the most common neoplasms associated with chronic epilepsy. Low grade astrocytomas or vascular malformations generate seizures due to chemical or mechanical effects of the lesion, the pacemaker area occurs obviously outside the lesion, in the adjacent brain tissue. Conversely, malformations of cortical development have intrinsic epileptogenicity. In them, the seizure onset zone is localized intralesional: the lesion generates seizures itself.     

颅脑外伤术后癫痫的防治

目的探索颅脑外伤术后癫痫发作的原因,并对预防及治疗应注意的问题进行探讨.方法对938例脑外伤手术后并发癫痫发作的33例患者进行分析,重点对术后的预防用药、易致癫痫发作原因及再次手术问题进行总结.结果 938例颅脑外伤术后并发癫痫发作33例,占3.5%,其中颅内感染16例,并发癫痫病例大多药物治疗效果好,对难治性癫痫药物无法控制的5例病例经再次手术均取得满意疗效.结论对脑外伤手术中的正确处理以及术后恰当的预防性用药等可以降低术后癫痫的发病率、减轻癫痫发作程度.     

Reversible memory disorders in an older patient caused by epilepsy

Memory impairment in a 63-year-old man was the most prominent expression of partial epileptic seizures from the temporal lobe, probably resulting from a head injury. Treatment with antiepileptic drugs resulted in complete recovery. This case illustrates that epilepsy should be considered in the differential diagnosis in elderly patients with an isolated memory disorder. The diagnosis is made by clinical methods and may be confirmed by electroencephalography.     

Recognizing syncope: pitfalls and surprises.

Loss of consciousness and falling are the key features of syncope. Common accompaniments include tonic and myoclonic muscle activity, eye deviations, automatisms, vocalizations and hallucinations which may render the distinction from epileptic seizures difficult. Differential diagnosis is based on the specific features and not the mere presence of these phenomena. Recognition of syncope depends also on accurate information about precipitants, premonitory symptoms and postictal events: the absence of postictal confusion has been identified as the single most powerful factor discriminating syncope from epileptic seizures whereas incontinence and head injury are common in both conditions. Investigations such as electroencephalogram, tilt testing and postictal prolactin or creatine kinase levels may be helpful but are never diagnostic in isolation. Exceptionally, hypoxic and epileptic mechanisms interact within a single attack.     

Clinical thinking and decision making in practice. A young women with muscle cramps

A 23-year-old woman with a history of episodic stiffening of the limbs since her early adolescence, reported attacks of muscle contraction accompanied by feelings of panic but without loss of consciousness. Epileptic seizures, e.g. progressive myoclonic epilepsy, metabolic encephalopathy, dystonia and tetany were suggested. During the examination, muscle contraction could be provoked whilst measuring the blood pressure. Tetany based on primary hypoparathyroidism was diagnosed from the medical history as well as the neurological examination. This was confirmed by laboratory tests. She was successfully treated with calcium and I-alpha-(OH)2 vitamin D3.     

Diagnosing Epilepsy During the Career Counselling Process: Treatment Suggestions

Research indicates that up to 50% of persons suffering from epilepsy also experience psychological problems. It is important not only to help patients distinguish between epileptic and non-epileptic seizures, but also to identify the presence of stress and stressors and to refer patients for appropriate therapy, which may include psychotherapy, behaviour therapy, physical exercise and identifying specific triggers (emotional triggers) to avoid seizures. Potential causes of and treatments for adolescent epilepsy, as well as the potential link between stress and seizures, are discussed. Four case studies, which exemplify the phenomenon of adolescent epilepsy, are presented. Therapeutic psychological and medical interventions have been successfully combined in the case of adolescents who were initially referred for career counselling but were subsequently diagnosed with epilepsy. It is suggested that the reason for referral will often have to be treated as secondary, while primary problems, such as epilepsy, will have to be dealt with first. Unless a "whole person medicine" (multidimensional) approach is adopted, the results of intervention may remain less than optimal.     

Treatment and long-term follow-up of post-anoxic myoclonus]

Postanoxic myoclonic (Lance-Adams) syndrome is characterized by myoclonic jerking provoked by intention or external stimuli. The authors present a patient in whom high-dose piracetam treatment resulted in a long-term improvement. Their female patient jumped into the river in order to commit a suicide. She was rescued in the state of clinical death. After a successful reanimation, she was comatose for 16 days. Despite the adequate rehabilitation therapy, her movement status did not change, due to jerking induced by external stimuli. Two months after the asphyxia, the patient was still confined to bed. The authors diagnosed her illness as Lance-Adams syndrome, based on the clinical history and symptoms. Valproic acid and clonazepam was introduced and, after a few days 24 g piracetam was added intravenously. After the first piracetam infusion, the jerking dramatically diminished, she was able to walk with some help. During the 4-years follow up, she received orally 19.2 g piracetam, 1500 mg valproic acid and 6 mg clonazepam. Now she is able to walk without help for a short distance and her cognitive functions have almost completely restituted. CONCLUSION: Lance-Adams syndrome is usually recognized only in a late phase, preventing the early rehabilitation. The trias consisting of anoxia, coma, and stimulus-sensitive myoclonus, however, can be easily recognized, and the adequate treatment may lead to a significant improvement.