Cingulate epileptogenesis in hypothalamic hamartoma

Hypothalamic hamartoma (HH) is a relatively rare cause of epilepsy, mainly affecting children. Nearly all patients develop gelastic seizures, often followed by other focal seizure types. Our case illustrates the mechanisms of epileptogenesis in HH. The patient developed gelastic attacks as a baby, and secondarily generalized seizures and drop attacks at 9 years of age. Magnetic resonance imaging (MRI) confirmed the presence of a HH. Presurgical assessment with intracranial electroencephalography (EEG) monitoring recorded gelastic seizures with generalized epileptiform activity. Functional stimulation of the hamartoma provoked gelastic attacks. Single pulse electrical stimulation (SPES) was used to identify epileptogenic cortex. SPES of the left cingular cortex provoked generalized responses similar to the spontaneous generalized discharges. Our results suggest that long-standing history of epilepsy in patients with HH may be related to additional sources of epileptogenic activity. Electrical stimulation performed in this patient provided additional data to favor the hypothesis of secondarily epileptogenesis in the cingulate gyrus independently from the primary origin in the HH.     

Cognitive functions in juvenile and adult patients with gelastic epilepsy due to hypothalamic hamartoma

PURPOSE: To describe extend and severity of cognitive deficits in juvenile and adult patients with gelastic seizures and hypothalamic hamartoma (HH) and to analyze the impact of epilepsy-related variables on cognitive performance. METHODS: Thirteen juvenile and adult patients (mean age, 25 years; seven men) underwent comprehensive neuropsychological testing assessing intellectual performance, attention and executive functions, verbal and visual memory, and visuospatial abilities. RESULTS: Intellectual abilities ranged from moderate mental retardation to good average performance; 54% of the patients displayed below-average global intellectual abilities. Attentional and executive functions were impaired in 23% to 46% of the patients. Below-average visuospatial capabilities were observed in 39% of the cases. Memory functions were impaired regarding both visual (77%) and verbal learning (62%). Nonparametric correlation analysis revealed a significant relation between monthly partial seizure frequency and reduced cognitive flexibility and reduced performance in mental rotation. In addition, HH volume was significantly negatively correlated with cognitive flexibility, whereas age at onset and duration of epilepsy did not show significant correlation to cognitive performance. CONCLUSIONS: More than half of the adult patients with gelastic seizures and HH displayed deficits in a broad range of cognitive functions, expressed mostly in visual and verbal learning and memory. Some of the deficits could be shown to correlate with disease-related characteristics representing the severity of the epilepsy or the size of the underlying lesion. These findings prompt for a longitudinal investigation of the development of these cognitive deficits to analyze further the relevant factors contributing to this wide spectrum of cognitive impairments.     

Callosotomy for generalized seizures associated with hypothalamic hamartoma

Abstract

A case is reported of intractable epilepsy associated with a hypothalamic hamartoma in an 18 year old man. The patient underwent a two-third anterior callsotomy and, subsequently, removal of the hamartoma. CaUosotomy did not affect the generalized seizure pattern. The authors believe this to be the first documented case of hypothalamic hamartoma in which callosotomy for seizure control was attempted. The poor response to callosotomy suggests the extracallosal diffusion of the generalized seizures from hypothalamic hamartomas. [Neurol Res 1993; 15: 139-141]     

EEG and video-EEG seizure monitoring has limited utility in patients with hypothalamic hamartoma and epilepsy

Purpose: Hypothalamic hamartomas (HHs) are a malformation of the ventral hypothalamus and tuber cinereum, associated with gelastic seizures and epilepsy. We sought to determine the spectrum of electroencephalography (EEG) abnormalities in a large cohort of HH patients. Methods: Data was collected for HH patients undergoing evaluation between 2003 and 2007. Data included seizure history, prior treatment, and results of diagnostic studies. After informed consent, data were entered into a database. Key Findings: We reviewed 133 HH patients. Mean age at time of data analysis was 15.7 years (59.4% male). Most patients had gelastic (77%) and/or complex partial seizures (58%). Records for 102 EEG studies on 73 patients were reviewed. Interictal epileptiform abnormalities were seen in 77%, localizing predominately to the temporal and frontal regions. Records for 104 video‐EEG (VEEG) studies on 65 patients were reviewed. Of 584 gelastic seizures (GS) captured, no ictal EEG change was noted in 438 (75%). Of GS with localizing features, 89% suggested onset from the temporal and/or frontal regions. There were 160 complex partial seizures (CPS). For those with localizing features, 100% localized to the temporal and/or frontal head regions. EEG and VEEG findings correlated with the side of HH attachment. VEEG did not influence outcome. Significance: EEG features in HH patients are diverse. The majority of gelastic seizures fail to demonstrate change in the EEG. The lack of EEG changes with many clinical seizures, and the false localization seen in those events with an ictal change suggest the utility of EEG is limited in the evaluation of these patients.     

Gelastic seizures due to hypothalamic hamartoma: Rapid resolution after endoscopic tumor disconnection

Gelastic epilepsy are focal seizures manifesting as recurrent brief seizures starting as laughter or grimaces. They are most commonly associated with other types of seizures and can be secondary to infectious, malformative, metabolic, or neoplastic processes involving the central nervous system. We report on an 18-month-old girl who presented since the age of 2 months with multiple, recurrent, unprovoked episodes of stereotypical laughter. Brain magnetic resonance study revealed an hypothalamic hamartoma. Endoscopic tumor disconnection of the hamartoma resulted in rapid resolution of neurological symptomatology.     

Transcallosal resection of hypothalamic hamartoma for intractable epilepsy

PURPOSE: To present the results of transcallosal surgical resection of hypothalamic hamartoma (HH) in 26 patients with refractory epilepsy in a prospective outcome study. METHODS: Patients with refractory epilepsy symptomatic to HH were referred for surgical resection of their HH (mean age, 10.0 years; range, 2.1-24.2 years). A transcallosal, interforniceal approach was used to remove and/or disconnect the hamartoma. Volumetry was obtained on pre- and postoperative brain MRI scans to determine percentage of resection. Outcome assessment included determination of postoperative seizure frequencies in comparison to baseline and the incidence of postoperative complications. Postoperative changes in cognitive and behavioral functioning, in comparison to baseline, were elicited by parental report. RESULTS: The average postoperative follow-up interval was 20.3 months (range, 13-28 months). Fourteen (54%) patients were completely seizure free, and nine (35%) had at least a 90% improvement in total seizure frequency. Parents reported postoperative improvement in behavior in 23 (88%) patients and in cognition in 17 (65%) patients. Transient postoperative memory disturbance was seen in 15 (58%) patients, but persisted in only two (8%). Two (8%) patients had persisting endocrine disturbance requiring hormone replacement therapy (diabetes insipidus and hypothyroidism in one each). With univariate analysis, the likelihood of a seizure-free outcome correlated with younger age, shorter lifetime duration of epilepsy, smaller preoperative HH volume, and 100% HH resection. CONCLUSIONS: Refractory epilepsy associated with HH can be safely and effectively treated with surgical resection by a transcallosal, interforniceal approach. Short-term memory deficits appear to be transient for most patients, and family perception of the impact of surgery on cognitive and behavioral domains is favorable. Complete resection yields the best result.     

Hypothalamic hamartoma and infantile spasms

PURPOSE: A small number of patients with hypothalamic hamartoma (HH) present with infantile spasms (IS) as an initial or early seizure type. We describe the clinical features of IS associated with HH. METHODS: Our series of patients with HH and epilepsy was reviewed to identify cases with a history of IS. The clinical features and neuroradiological findings in this study group were compared to a control group of patients with HH and refractory epilepsy, but without a history of IS. RESULTS: We identified six patients with HH and a history of IS in this series (n = 122, 4.9%). Five of the six are male. Four of the six patients (67%) developed IS as their first seizure type. The mean age for onset of IS was 6.2 months (range 4-9 months). Results of electroencephalographic (EEG) study at the time of IS diagnosis showed hypsarrhythmia in two (33%). Five patients were treated with adrenocorticotropic hormone (ACTH), and four of the five (80%) responded with control of IS. However, these patients developed other seizure types, and were ultimately refractory to medical management. Aside from the IS, no significant differences in clinical and imaging features were determined between the study group and the control group. CONCLUSIONS: HH should be included in the differential diagnosis for infants presenting with IS. These patients may have hypsarrhythmia on initial EEG, and may respond to ACTH treatment with improvement of IS. However, all became refractory with other seizure types, more commonly seen in HH patients. Focal pathologies associated with IS may be subcortical, as well as cortical, in nature. We have not identified any predictive features for the occurrence of IS in the HH population.     

Transcallosal resection of hypothalamic hamartoma for gelastic epilepsy

Introduction Hypothalamic hamartomas (HHs) are commonly associated with severe epilepsy resistant to anticonvulsant therapy. Historically, surgical resection of HHs resulted in considerable morbidity. Discussion Two series of patients who successfully underwent resection using a transcallosal approach have now been published; we report the first UK experience of this technique in a series of five patients with HHs and gelastic epilepsy resistant to anticonvulsant therapy. Patients were assessed pre- and postoperatively for seizure activity, endocrine function, ophthalmology, and neurocognitive function. Two patients had precocious puberty and all had evidence of developmental delay and behavioral problems. Postoperatively, all children experienced at least a 50% reduction in seizure frequency with abolition of major seizure types; one child remains seizure-free. One child developed a mild postoperative right hemiparesis and one developed transient diabetes insipidus. Conclusion There were no adverse developmental effects of surgery. Transcallosal resection of HHs ameliorates resistant epilepsy syndromes associated with HH.     

The clinical spectrum of epilepsy in children and adults with hypothalamic hamartoma

PURPOSE: Hamartomas of the hypothalamus (HH) cause an uncommon and unusual epilepsy syndrome. The condition is recognized to affect children, but the presentation in adults is not well understood. We present 19 children and adult patients with HH, including three patients whose epilepsy began in adult life. The patterns of clinical presentation, evolution of the epilepsy from childhood to adult life, and electroclinical diagnostic features are presented. METHODS: Nineteen patients, both children and adults with HH and epilepsy, were evaluated clinically, with EEG, video-EEG, and magnetic resonance imaging (MRI) scanning. Seven patients underwent surgical resection of the hamartoma. Stereotactic thermocoagulation of the hamartoma was performed in two patients. RESULTS: Gelastic seizures occurred at onset of epilepsy in 15 of 16 early-onset cases. Subsequently, multiple seizures types occurred, which then evolved to mainly partial epilepsy with tonic or complex partial seizures (five of eight adults), or became entrenched symptomatic generalized epilepsy with atypical absences, drop attacks, and secondarily generalized seizures, and cognitive impairment (three of eight adults). In the adult-onset patients, gelastic seizures were not prominent, the epilepsy was milder, and they functioned normally. Stereotactic thermocoagulation of the hamartoma resulted in improvement in seizure control in two patients. CONCLUSIONS: Gelastic seizures are not a prominent feature of epilepsy in adult patients with HH. The epilepsy associated with HH, although severe at onset, can evolve into a milder syndrome in later life. For less severely affected patients, minimally invasive alternatives to the traditionally difficult open surgical treatment should be considered.     

下丘脑错构瘤

目的：报告５例下丘脑错构瘤的临床表现、诊断及治疗。方法：分析５例下丘脑错构瘤的病史，临床表现及诊断、治疗情况，结合文献加以分析讨论。结果：５例皆在儿童早期发病，均有性早熟，其中３例有痴笑样癫痫，其它可有癫痫大发作，行为异常或智力减退，有２例手术治疗取得了较好疗效。病理可见神经元结构，电镜显示神经元内有分泌颗粒。结论：下丘脑错构瘤可以手术治疗，药物治疗对性早熟有效，而对痴笑样癫痫无效     

Clinical characteristics and long-term outcome of surgery for hypothalamic hamartoma in children with refractory epilepsy

Context:

Hypothalamic hamartomas (HH) are ectopic masses of neuronal and glial tissue most commonly presenting with medically refractory gelastic seizures with evolution to other seizure types. They are also associated with cognitive and behavioral problems to varying extent. Surgery has been found to improve quality of life in more than 50% of patients.

Aim:

To evaluate the clinical characteristics and long-term outcome of surgery in children with HH and refractory epilepsy.

Materials and Methods:

A retrospective analysis of presurgical, surgical, and postsurgical data of six children who underwent surgery for HH and had at least 3 years follow-up was performed.

Results:

Six children (male: female = 5:1) aged 3-16 years (at the time of surgery) underwent surgical resection of HH for refractory epilepsy. At last follow-up (range 3-9 years), three children were in Engel''s class I, two in Class II, and one in class III outcome. Significant improvement in behavior, quality of life was noted in four children; while the change in intelligence quotient (IQ) was marginal.

Conclusions:

Medically refractory epilepsy associated with behavioral and cognitive dysfunction is the most common presentation of HH. Open surgical resection is safe with favorable outcome of epilepsy in 50% with significant improvement in behavior and marginal change in cognitive functions.     

Gelastic seizures: Incidence,clinical and EEG features in adult patients undergoing video‐EEG telemetry

This study aimed to determine clinical features of adult patients with gelastic seizures recorded on video –electroencephalography (EEG) over a 5‐year period. We screened video‐EEG telemetry reports for the occurrence of the term “gelastic” seizures, and assessed the semiology, EEG features, and duration of those seizures. Gelastic seizures were identified in 19 (0.8%) of 2,446 admissions. The presumed epileptogenic zone was in the hypothalamus in one third of the cases, temporal lobe epilepsy was diagnosed in another third, and the remainder of the cases presenting with gelastic seizures were classified as frontal, parietal lobe epilepsy or remained undetermined or were multifocal. Gelastic seizures were embedded in a semiology, with part of the seizure showing features of automotor seizures. A small proportion of patients underwent epilepsy surgery. Outcome of epilepsy surgery was related to the underlying pathology; two patients with hippocampal sclerosis had good outcomes following temporal lobe resection and one of four patients with hypothalamic hamartomas undergoing gamma knife surgery had a good outcome.     

Hypothalamic hamartoma: the role of surgery in a series of eight patients

Hypothalamic hamartoma are rare lesions. We report a new series of eight patients treated for precocious puberty (six cases) or gelastic seizures (two cases). Surgical resection was total in four cases (three pediculated and one sessile). Precocious puberty was controlled by surgical treatment in all cases. Gelastic seizures were controlled by medical treatment, but the patients did not become seizure free. We observed no mortality and no endocrinological or visual morbidity. The fact that a vascular ”rete mirabilis” was observed on the surface of the lesion in our surgical material is an argument favoring a vascular mechanism in precocious puberty. Coagulation of this vascular structure can help control precocious puberty. Our series confirms that the hypothalamic hamartoma can be surgically treated when patients fail to respond to medical treatment, when the length of the treatment cannot be tolerated by the chidren and their families, and when there are uncontrolled gelastic seizures Received: 14 February 2000     

儿童下丘脑错构瘤导致癫痫的手术治疗

目的 探讨儿童下丘脑错构瘤导致癫痫的手术治疗。方法 报告儿童下丘脑错构瘤11例，男6例，女5例，年龄为2-15岁，发病年龄为2个月至14岁。首发症状为痴笑样癫痫者10例。为癫痫大发作者1例，伴发性早熟6例，伴发跌倒发作3例，伴发癫痫大发作6例。手术；翼点入路10例，终板入路1例，术中错构瘤深部电极检测4例。结果 全切错构瘤2例，大部切除8例，部分切除1例。术中错构瘤深部电极显示棘波1例。随诊19至90个月，痊愈2例，有效9例，术后一过性动眼神经麻痹3例。结论 手术切除错构瘤可有效治疗儿童下丘脑错构瘤导致的癫痫。     

Seizure ending signs in patients with dyscognitive focal seizures*

Aim. Signs indicating the end of a focal seizure with loss of awareness and/or responsiveness but without progression to focal or generalized motor symptoms are poorly defined and can be difficult to determine. Not recognizing the transition from ictal to postictal behaviour can affect seizure reporting accuracy by family members and may lead to delayed or a lack of examination during EEG monitoring, erroneous seizure localization and inadequate medical intervention for prolonged seizure duration. Methods. Our epilepsy monitoring unit database was searched for focal seizures without secondary generalization for the period from 2007 to 2011. The first focal seizure in a patient with loss of awareness and/or responsiveness and/or behavioural arrest, with or without automatisms, was included. Seizures without objective symptoms or inadequate video‐EEG quality were excluded. Results. A total of 67 patients were included, with an average age of 41.7 years. Thirty‐six of the patients had seizures from the left hemisphere and 29 from the right. All patients showed an abrupt change in motor activity and resumed contact with the environment as a sign of clinical seizure ending. Specific ending signs (nose wiping, coughing, sighing, throat clearing, or laughter) were seen in 23 of 47 of temporal lobe seizures and 7 of 20 extra‐temporal seizures. Conclusions. Seizure ending signs are often subtle and the most common finding is a sudden change in motor activity and resumption of contact with the environment. More distinct signs, such as nose wiping, coughing or throat clearing, are not specific to temporal lobe onset. A higher proportion of seizures during sleep went unexamined, compared to those during wakefulness. This demonstrates that seizure semiology can be very subtle and arousals from sleep during monitoring should alert staff. Patient accounts of seizure frequency appear to be unreliable and witness reports need to be taken into account. [Published with video sequences]     

长程视频脑电监测在下丘脑错构瘤诊断治疗中的应用(附5例报告)

目的探讨长程视频脑电监测在下丘脑错构瘤诊断治疗中的应用意义。方法回顾性分析5例下丘脑错构瘤长程视频脑电(VEEG)特征,VEEG结合磁共振成像(MRI)、发作间期正电子发射计算机断层扫描(PET)检查诊断定位。结果发作间期清醒平静状态脑电图表现:双侧波形均呈不对称表现,双侧存在广泛单发性棘慢波或者双侧广泛不规则θ或δ波,一侧波幅优势,主要为一侧额叶优势,2例左侧优势,3例右侧优势,优势侧别同MRI显示的错构瘤侧别一致;睡眠期脑电图表现:存在基本睡眠标志波形与睡眠周期,间有较多量棘慢波或多棘慢波,存在形式同间期清醒平静状态;5例均捕获临床发作过程,共计13次,其中痴笑发作8次、痴笑发作继发全身强直阵挛5次,发作期脑电图表现:3例为去同步化低电压数秒后EEG混合肌电干扰,2例以肌电伪差为主。MRI结果:下丘脑脚间池处部位可见占位性改变,位于左侧半球2例、右侧半球3例。PET结果:MRI所提示的占位性改变区域均显示低代谢。5例均手术彻底去除错构瘤,随访5例患者术后均无痴笑发作或继发全身强直阵挛。结论长程视频脑电监测结合MRI及PET检查对下丘脑错构瘤诊断定位准确性高,手术治疗下丘脑错构瘤是最佳选择。     

Functional brain mapping of ictal activity in gelastic epilepsy associated with hypothalamic hamartoma: A case report

Hypothalamic hamartomas (HHs) have been demonstrated as the cause of gelastic epilepsy, both by intracranial electrodes and functional imaging. The neocortex becomes secondarily involved, through poorly characterized propagation pathways. The detailed dynamics of seizure spread have not yet been demonstrated, owing to the limited spatial–temporal resolution of available functional mapping. We studied a patient with epilepsy associated with HH and gelastic epilepsy. Simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) of several seizure events were obtained, with blood oxygen level dependent (BOLD) activation of the hamartoma, and left hemisphere hypothalamus, hippocampus, parietal–occipital area, cingulate gyrus, and dorsal–lateral frontal area. Integration of regional BOLD kinetics and EEG power dynamics strongly suggests propagation of the epileptic activity from the HH through the left fornix to the temporal lobe, and later through the cingulate fasciculus to the left frontal lobe. The EEG/fMRI method has the spatial–temporal resolution to study the dynamics of seizure activity, with detailed demonstration of origin and propagation pathways.     

下丘脑错构瘤214例临床特征分析

目的 分析下丘脑错构瘤的临床特征.方法 回顾分析1994年1月至2008年5月北京天坛医院诊治的214例下丘脑错构瘤的临床资料.结果 性别:男性多于女性,男女之比为1.52:1;有性早熟的115例中,男女之比为1.09:1;有癫痫的123例中男女之比为2.15:1;有痴笑样癫痫的96例中男女之比为2:1;同时表现为性早熟及癫痫的38例中男女之比为1.38:1.发病年龄:200例有症状的病例,平均发病年龄为34.5个月;发病年龄≤3岁者157例,占78.5%;单纯性早熟者77例(38.5%),平均发病年龄16.5个月,<3岁者67例,占87%;表现有性早熟者115例(57.5%),平均发病年龄为17.63个月,发病<3岁者99例,占86.1%;有痴笑样癫痫者96例(48%),平均为26.14个月,<3岁者有78例,占81.3%;所有癫痫者[痴笑样癫痫和(或)癫痫大、小发作]123例(61.5%),平均发病年龄为3.81岁,≤3岁前发病者有90例,占73.2%.结论 下丘脑错构瘤多数在婴幼儿期发病,男性多于女性.     

Ictal bradycardia in a patient with a hypothalamic hamartoma: a stereo-EEG study

Little is known about bradycardia and cardiac asystole which occur during partial epileptic seizures, especially whether they relate to ictal involvement of well-defined cortical areas. Several reports based on simultaneous electrocardiographic and intracranial depth electroencephalographic monitoring have shown that either the fronto-orbital cortex or the amygdalohippocampal complex could be responsible for such cardiac variations. We performed stereo-EEG recordings in a patient with refractory localization-related epilepsy associated with a hypothalamic hamartoma. We found that other cortical areas, such as the frontocentral region and the temporal neocortex, can contribute to the genesis of ictal bradyarrhythmia. Second, the lesion per se, although located within the hypothalamus, is not involved with this phenomenon.