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.     

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]     

Semiologic aspects of epileptic seizures in 31 patients with hypothalamic hamartoma

Purpose: Characterization of seizure semiology in patients with hypothalamic hamartoma (HH) based on video–electroencephalography (EEG) monitoring (VEM). Methods: We retrospectively analyzed seizure semiology of 31 patients (20 male, mean age 23.5 years) who underwent VEM at the University Hospitals Freiburg or Heidelberg, Germany. Inclusion criteria were magnetic resonance evidence of an HH, no prior surgical or radiosurgical treatment, and at least two video‐documented seizures. A total of 263 seizures were included (mean number of seizures/patient 8.5, range 2–10). To analyze age‐dependent changes in seizure semiology, patients were grouped into “children” (3–11 years, n = 5), “adolescents” (12–17 years, n = 4), and “adults” (≥18 years, n = 22). Results: According to patient history, gelastic seizures had occurred in all patients, in 74% as the initial seizure type at epilepsy onset. In VEM, epileptic laughter varied from facial grinning to intense contractions of the diaphragm and body shaking. Unilateral motor signs were seen ipsi‐ and contralaterally to the HH. Tonic seizures were frequent and did not depend on the state of vigilance. Children, in contrast to adults and adolescents, did not show secondarily generalized tonic–clonic seizures, the gelastic component was the dominating and initial semiologic element, and seizures were significantly shorter. Conclusion: Seizure semiology is highly variable and age dependent. This may reflect network modulations with different propagation of ictal activity and/or secondary epileptogenesis. Detailed knowledge about such changes may contribute to both earlier recognition of seizures during childhood and better assignment of seizure types to a hypothalamic origin.     

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.     

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.     

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.     

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.     

立体脑电图引导射频热凝毁损治疗下丘脑错构瘤继发癫痫

目的探讨立体脑电图(SEEG)引导射频热凝毁损技术在下丘脑错构瘤继发癫痫治疗中的临床应用价值。方法回顾性分析2015年6月至2018年1月北京丰台医院神经外科接受SEEG引导射频热凝毁损治疗的7例下丘脑错构瘤继发癫痫患者的临床资料,包括详细病史、症状学、脑电图及影像学资料。术前评估考虑下丘脑错构瘤为致痫灶,随后利用立体定向框架于下丘脑错构瘤处植入SEEG电极,并行视频脑电监测,根据SEEG的放电区域进行射频热凝毁损术。若毁损后癫痫样放电未消失,则进行第二次毁损,直至癫痫样放电消失。分析术后并发症,并进行电话或门诊随访,应用Engel分级进行预后评估。结果7例患者热凝毁损术后的平均随访时间为(19.6±11.1)个月,其中5例患者的癫痫发作消失(Engel分级Ⅰ级),1例患者毁损术后的癫痫发作频率减少约75%(Engel分级Ⅲ级),1例患者毁损术后的癫痫发作频率未明显改善(Engel分级Ⅳ级)。3例患者术后早期出现高热、嗜睡、尿崩症、电解质紊乱及记忆力下降等并发症,经治疗后均恢复。结论本研究初步认为SEEG引导的射频热凝毁损术是治疗下丘脑错构瘤继发癫痫安全、有效的治疗手段。在诊断明确的前提下完全离断错构瘤基底与下丘脑的联系是癫痫控制的关键。     

Insular-opercular seizures manifesting with sleep-related paroxysmal motor behaviors: a stereo-EEG study

Purpose: Sleep‐related complex motor seizures are a common feature of nocturnal frontal lobe epilepsy. Nevertheless, recent studies also suggest that sleep‐related hypermotor seizures can originate in the insula. The present study describes the electroclinical features of eight drug‐resistant epileptic patients with insular‐opercular seizures manifesting with nocturnal complex motor seizures. Methods: Patients underwent a comprehensive presurgical evaluation, which included history, interictal electroencephalography (EEG), scalp video‐EEG monitoring, high‐resolution magnetic resonance imaging (MRI), and intracerebral recording by stereo‐EEG. Key Findings: Almost all patients reported an initial sensation consisting of viscerosensitive or somatosensory symptoms. Ictal clinical signs were represented by tonic–dystonic asymmetric posturing and/or hyperkinetic automatisms, including bimanual/bipedal activity and ballistic movements. Some patients exhibited dysarthric speech, hypersalivation, and apnea. Interictal and ictal EEG provided lateralizing information in the majority of patients. In three patients, MRI showed a focal anatomical abnormality in the insular‐opercular region. Stereo‐EEG ictal recordings demonstrated that the epileptic discharge involved simultaneously the insular cortex and the opercular region. Complex motor manifestations appeared when the ictal discharge showed an extrainsular spreading to frontomesial regions (cingulum, superior frontal gyrus, and supplementary motor area) and/or to internal and neocortical temporal lobe structures. Six patients received an insular‐opercular cortical resection; three of them are seizure free (minimum follow‐up 24 months) and in one a marked reduction in seizure frequency was obtained. Two patients have been operated on recently. Histology revealed a focal cortical dysplasia in three patients. One patient excluded from surgery died for sudden unexpected death in epilepsy during sleep. Significance: Our data strengthen the concept that sleep‐related complex motor attacks can originate in the insula, and provide useful electroclinical information to differentiate this localization from those with similar clinical characteristics. Furthermore, this study indicates that in these drug‐resistant patients, surgical treatment represents a highly effective treatment option.     

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.     

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.     

Sequential analysis of fMRI images: A new approach to study human epileptic networks

Purpose: The aim of this study was to introduce a new approach for analysis of functional magnetic resonance imaging (fMRI) data in order to illustrate the temporal development of the blood oxygenation level–dependent (BOLD) signal changes induced by epileptic seizures. Method: In order to sequentially analyze the fMRI images acquired during epileptic seizures, a continuous series of echo planar imaging (EPI) scans covering the complete period of a seizure was acquired. Data were segmented into 10‐s blocks. Each block, representing a unique experimental condition, was contrasted with a neutral (no seizure) baseline condition. Visual comparison of the activations from one block to the next highlighted the course of activations and deactivations during the seizure event. This analysis was applied to three independent seizures of one patient with peri‐rolandic epilepsy secondary to chronic encephalitis: one seizure before epilepsy surgery and two after unsuccessful tailored resection. Observations were compared to results from invasive subdural electroencephalography (EEG) monitoring, single‐photon emission computed tomography (SPECT) coregistered to MRI (SISCOM), and independent component analysis (ICA), a model‐free method of BOLD‐signal analysis. Results: The initial increase in BOLD signal occurred 10–40 s before clinical onset in the same location compared to the seizure‐onset zone determined by invasive subdural evaluation and SISCOM. Sequential involvement of cortical and subcortical structures was in agreement with SISCOM, intracranial EEG recordings, and ICA results. Discussion: In selected patients, sequential analysis of changes in BOLD signal induced by epileptic seizures might represent a useful approach for investigating the temporal development of brain activity during epileptic seizures, thereby allowing imaging of those cerebral structures involved in seizure generation and propagation.     

Ictal Laughter Associated with Paroxysmal Hypothalamopituitary Dysfunction

Summary: Purpose : Seizures with ictal laughter (also termed gelastic seizures) have been associated with hypothalamic hamartomas and precocious puberty. It is not known, however, where in the brain such seizures originate. We describe a child with gelastic seizures and a hypothalamic lesion (probably a hamartoma) in whom two dysfunctional phenomena were observed.
Results : First, there was a hyperperfusion in the hypothalamopituitary areas shown by ictal [^99m]Tc hexamethyl-propyleneamine oxime (HM-PAO) single photon-emission computed tomography (SPECT). Second, there was an ictal pulse of gonadotropins, 17β-estradiol, and growth hormone well above the normal limits in one of the seizures.
Conclusion : These findings suggest that gelastic seizures associated with hypothalamic hamartomas are generated in the hypothalamus or in its neighboring regions and that these seizures may cause paroxysmal dysfunction of the hypothalamo-pitutary axis.     

Ictal headache: headache as first ictal symptom in focal epilepsy

Headache may be associated with seizures as a preictal, ictal, or postictal phenomenon, but it is often neglected because of the dramatic neurological manifestations of the seizure. Headache can also be the sole or predominant clinical manifestation of epileptic seizures, although this is a relatively rare condition. We describe two cases of focal symptomatic drug-resistant epilepsy with headache as the first ictal symptom. In both cases, the headache, which lasted a few seconds, was contralateral to the ictal discharge and did not have the clinical features of migraine. Ictal headache is a rare epilepsy symptom that can help to localize ictal EEG discharges. Recently, the term ictal epileptic headache has been proposed in cases in which headache is the sole ictal epileptic manifestation Diagnosis requires the simultaneous onset of headache with EEG-demonstrated ictal discharges.     

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.     

Ictal vomiting in association with left temporal lobe seizures in a left hemisphere language-dominant patient

Ictal vomiting is considered a localizing sign indicating nondominant lateralization in patients with partial seizures of temporal lobe origin. We report a case of ictal vomiting associated with left temporal seizure activity in a left hemisphere language-dominant patient with a left mesial temporal glioma. Bilateral mesial temporal depth electrodes helped verify seizure lateralization. Surgery consisting of tumor resection and a left anterior temporal lobectomy and amygdalohippocampectomy resulted in freedom from seizures and episodes of vomiting. This case indicates that ictal vomiting can occur as a manifestation of left temporal onset seizures in left hemisphere-dominant patients.     

A case of hypothalamic hamartoma associated with arachnoid cyst

A 14-year-old girl presented with seizures. Radiological examinations revealed an arachnoid cyst in left middle fossa and a cystic mass in the interpeduncular cistern. The cyst was opened and the wall of the cyst and a mass were biopsied. The histological findings were characteristic of an arachnoid cyst and hamartoma, respectively. A hypothalamic hamartoma associated with an arachnoid cyst is comparatively rare; however, such a case may help clarify the genesis of this malformation. Received: 5 November 1998 Accepted: 19 January 1999     

Utility of the Scalp-Recorded Ictal EEG in Childhood Epilepsy

PURPOSE: To evaluate the usefulness of the scalp-recorded ictal EEGs in diagnosing childhood epilepsy. METHODS: We analyzed the ictal EEGs of 259 seizures in 183 patients who visited the department of child neurology, Okayama University Medical School, during the past 6 years. RESULTS: We divided all seizures into the following four categories, according to the diagnostic usefulness of ictal EEGs in determining the seizure type: 1. (a) Ictal EEGs confirmed the diagnosis of the seizure type based on seizure symptoms (101 seizures); (b) Ictal EEGs aided in the classification of the seizure type based on the seizure symptoms (101 seizures); (c) Ictal EEGs corrected errors in the classification (37 seizures); and (d) Ictal EEGs revealed previously unreported/undocumented seizure type (20 seizures). 2. Of the 37 misdiagnosed seizures (group C), 11 were nonepileptic seizures misdiagnosed as epileptic seizures, eight were complex partial seizures (CPS) misdiagnosed as the other seizure types, and 10 were other seizure types misdiagnosed as CPSs. 3. Of the 20 previously unreported/undocumented seizures (group D), nine were myoclonic seizures, five were absence seizures, five were CPS, and one was tonic spasms. 4. Seventy-two patients had CPS. Among them, 11 patients showed no epileptic spikes in their interictal EEG recordings. Therefore, ictal recordings confirmed the diagnosis of epilepsy. CONCLUSIONS: Ictal EEG recording is a very useful diagnostic tool not only for determining seizure types, but also for uncovering the existence of the unsuspected seizure types. It supplies the physician with useful information for the classification and the treatment of epilepsy. In particular, ictal EEGs are useful in diagnosing patients with CPS.     

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。