Intractable gelastic seizures during infancy: ictal positron emission tomography (PET) demonstrating epileptiform activity within the hypothalamic hamartoma

Gelastic seizures comprise a very rare form of epilepsy. They present with recurrent bursts of laughter voices without mirth and are most commonly associated with the evolution of a hypothalamic hamartoma. The purpose of this article is to describe the second reported ictal fluorodeoxyglucose-positron emission tomography study in a unique case of an infant with intractable gelastic seizures since the neonatal period associated with a hypothalamic hamartoma. The patient presented at 4 months old with recurrent, almost persistent, gelastic seizures consisting of laughter bouts without mirth. The seizures were noticeable at the first week of life and increased in frequency to last up to 12 hours, namely status gelasticus. These gelastic fits were accompanied with focal motor seizures, including unilateral right-eye blinking and mouth twitching. Developmental mile-stones were intact for age. Magnetic resonance imaging of the cortex demonstrated a large hypothalamic hamartoma within the third ventricle, hampering cerebrovascular fluid drainage of the lateral ventricles. An electroencephalography was nondiagnostic. Ictal fluorodeoxyglucose-positron emission tomography demonstrated a large circumscribed hypermetabolic region within the location of the hypothalamic hamartoma, representing localized intense epileptiform activity. The infant became instantly free of all seizure types given minute doses of oral benzodiazepine (clonazepam) and remains completely controlled after 12 months. Her overall development remains intact. This ictal fluorodeoxyglucose-positron emission tomography is the second reported study verifying that the main source of the epileptic activity inducing gelastic seizures originates from the hypothalamic hamartoma itself; therefore, a complementary fluorodeoxyglucose-positron emission tomography study should be considered in any patient presenting with intractable gelastic seizures, especially in those associated with hypothalamic hamartoma, in order to localize the region of epileptiform activity amenable to surgical resection if intensive drug therapy fails.     

非下丘脑性发笑性癫痫发作的定位定侧分析

目的 分析发笑性癫痫发作患者的临床特点,以确定癫痫病灶位置,为手术治疗提供参考.方法 回顾性分析本院就诊10例发笑癫痫发作患者的临床特点,包括发作的特点、影像学的特征以及手术治疗结果等.结果 10例患者均接受手术治疗,其中8例完成分期颅内电极埋置.术后8例达到Engle Ⅰ级缓解,1为Ⅱ级,另外1例术后发作无明显改变.结论 非下丘脑病损所致发笑样癫痫发作者若不伴有情感症状出现,病灶多在额叶,并以辅助运动区为常见,伴有情感症状者多定位于颞叶.同时,发笑症状在发作过程的早期或者单独出现者定位很可能位于右侧大脑半球,反之,在晚期出现应考虑在左侧大脑半球的定位.     

Contralateral smile and laughter, but no mirth, induced by electrical stimulation of the cingulate cortex

The cerebral representation of laughter is dissociated. The emotional aspects seem to be processed in the temporal lobe; whereas the motor features apparently rely on the frontal cortex. In a few prior studies of patients in whom laughter was elicited by electrical stimulation (ES), it always was associated with mirth. We report a patient in whom ES in the right cingulate gyrus elicited smile and laughter, but no mirth. At low voltages, smiling was seen first contralaterally and became bilateral with increasing currents. Our observation supports the concept of the motor representation of laughter in the mesial frontal cortex.     

Gelastic seizures with dancing arising from the anterior prefrontal cortex

Aim. This case report provides insight into the function of the anterior prefrontal cortex (aPFC), specifically Brodmann Area 10 (BA10), and its interconnectivity. Method. We present a 10‐year‐old patient with lesional epilepsy and ictal onset, localised to BA10 in the aPFC. Results. Thirty‐four seizures were recorded. All seizures involved a demonstration of elation with laughter that was associated with a variety of different patterns of complex motor behaviour that included performing specific celebratory movements and acting out a Michael Jackson dance move. Electrographically, the seizures were all stereotyped and arose from the right frontal region, followed by a distinct left temporal ictal rhythm that corresponded with the onset of the behaviours. The lesion in the right aPFC was identified as a mixed lesion with both dysembryoplastic neuroepithelial tumour cells and type II cortical dysplasia. Conclusion. The electrographic analysis and unique seizure semiology suggest a connection between the aPFC and the contralateral temporal lobe. This neural pathway appears to be involved in the activation of previously formed procedural memories, creating an intensely positive emotional experience.     

Late-onset isolated gelastic epilepsy secondary to entrapment of the right temporal horn

The case is reported of a 70 year-old woman with isolated gelastic seizures (GS) secondary to a rare form of focal obstructive hydrocephalus, called entrapment of the lateral horn. Laughing attacks started five years after conservative intracranial surgery for a giant basilar aneurysm. Serial neuro-imaging studies revealed a progressive cystic enlargement of the right temporal horn, damaging the baso-lateral temporal cortex. An ictal EEG recording confirmed the epileptic nature of laughing attacks, and showed that the epileptiform activity originated in the right temporal lobe. Complete seizure control was achieved with current doses of diphenilhydantoin. Analysis of this and other previously reported cases, indicate that symptomatic GS may originate in multiple sites of both cerebral hemispheres, although related to the limbic system. The fact that this case exhibited isolated GS stresses the importance of the baso-lateral temporal cortex in the genesis of this type of seizures.     

Epilepsy in hypothalamic hamartoma: clinical and EEG features

Hypothalamic hamartoma (HH) is a congenital malformation of the hypothalamus that may be asymptomatic or manifest with precocious puberty or seizures. Gelastic seizures often begin early in life, even in the newborn period, being manifest by frequent attacks of inappropriate laughter resulting from seizure activity in the HH. The scalp electroencephalogram (EEG) is often normal in children with gelastic seizures, such that the diagnosis of epilepsy and the finding of a HH are often delayed. In a proportion of children with HH, there is an epileptic progression, in which complex partial seizures with frontal, temporal, and lateralized clinical features appear, usually with the appearance of focal slowing and epileptiform activity on the interictal EEG. Further progression may ensue with the appearance of tonic or atonic drop attacks, generalized tonic-clonic seizures, and epileptic spasms; rarely, infantile spasms may be the presenting seizure type. With the appearance of generalized seizures, the interictal EEG shows bilaterally synchronous and generalized epileptiform activity, often in abundance. The mechanism of this evolution is incompletely understood but neocortical seizure propagation and secondary epileptogenesis are believed to be important. Paralleling the development of the focal and generalized electroclinical manifestations in children with HH is usually slowing of development and the appearance of behavioral problems. Fortunately, many of these neurologic manifestations can be arrested, or reversed, with effective surgical treatment directed at the HH.     

Magnetoencephalography and diffusion tensor imaging in gelastic seizures secondary to a cingulate gyrus lesion

Gelastic seizures are relatively uncommon and rarely observed secondary to frontal lobe lesions. This report presents magnetoencephalography (MEG) and diffusion tensor imaging (DTI) findings in an adolescent with gelastic seizures secondary to a left anterior cingulate gyrus lesion. Ictal scalp video EEG showed bilateral frontal 4 Hz theta discharges. Interictal EEG showed left fronto-temporal spikes or sharp waves. Interictal MEG showed spike sources over bilateral temporal regions. DTI and tractography delineated slightly shifted corpus callosum posterior to the lesion, unaffected uncinate and inferior longitudinal fasciculi. The patient became seizure free for 12 months after surgical excision of a pleomorphic xanthoastrocytoma in the left anterior cingulate region. In our patient, MEG and EEG did not localize the deep-seated epileptogenic zone. The combination of DTI and neurophysiologic studies, however, possibly disclosed neuronal connections within the epileptic network and indicated that epileptic discharges propagated via the uncinate fibers from the primary epileptogenic zone in the anterior cingulate region to the mesial temporal region in this case with gelastic seizures secondary to a cingulate lesion.     

Gelastic epilepsy without hypothalamic hamartoma: Three additional cases

We describe three children with gelastic seizures without hypothalamic hamartoma whose seizures were characterized by typical laughing attacks associated or not with other seizure types. Ictal/interictal EEG and magnetic resonance imaging were performed. All three subjects showed a good response to carbamazepine therapy with complete seizure control in addition to a benign clinical and cognitive outcome. These three cases confirm that gelastic epilepsy without hypothalamic hamartoma, both in cryptogenic or symptomatic patients (one child showed a dysplastic right parietotemporal lesion), usually has a more benign natural history, and carbamazepine seems to be the most efficacious therapy to obtain both immediate and long-term seizure control. These findings need to be confirmed in a larger sample of children affected by gelastic epilepsy without hypothalamic hamartoma.     

Dacrystic seizures: Demographic,semiologic, and etiologic insights from a multicenter study in long‐term video‐EEG monitoring units

Purpose: To provide an estimate of the frequency of dacrystic seizures in video‐electroencephalography (EEG) long‐term monitoring units of tertiary referral epilepsy centers and to describe the clinical presentation of dacrystic seizures in relationship to the underlying etiology. Methods: We screened clinical records and video‐EEG reports for the diagnosis of dacrystic seizures of all patients admitted for video‐EEG long‐term monitoring at five epilepsy referral centers in the United States and Germany. Patients with a potential diagnosis of dacrystic seizures were identified, and their clinical charts and video‐EEG recordings were reviewed. We included only patients with: (1) stereotyped lacrimation, sobbing, grimacing, yelling, or sad facial expression; (2) long‐term video‐EEG recordings (at least 12 h); and (3) at least one brain magnetic resonance imaging (MRI) study. Key Findings: Nine patients (four female) with dacrystic seizures were identified. Dacrystic seizures were identified in 0.06–0.53% of the patients admitted for long‐term video‐EEG monitoring depending on the specific center. Considering our study population as a whole, the frequency was 0.13%. The presence of dacrystic seizures without other accompanying clinical features was found in only one patient. Gelastic seizures accompanied dacrystic seizures in five cases, and a hypothalamic hamartoma was found in all of these five patients. The underlying etiology in the four patients with dacrystic seizures without gelastic seizures was left mesial temporal sclerosis (three patients) and a frontal glioblastoma (one patient). All patients had a difficult‐to‐control epilepsy as demonstrated by the following: (1) at least three different antiepileptic drugs were tried in each patient, (2) epilepsy was well controlled with antiepileptic drugs in only two patients, (3) six patients were considered for epilepsy surgery and three of them underwent a surgical/radiosurgical or radioablative procedure. Regarding outcome, antiepileptic drugs alone achieved seizure freedom in two patients and did not change seizure frequency in another patient. Radiosurgery led to moderately good seizure control in one patient and did not improve seizure control in another patient. Three patients were or are being considered for epilepsy surgery on last follow‐up. One patient remains seizure free 3 years after epilepsy surgery. Significance: Dacrystic seizures are a rare but clinically relevant finding during video‐EEG monitoring. Our data show that when the patient has dacrystic and gelastic seizures, the cause is a hypothalamic hamartoma. In contrast, when dacrystic seizures are not accompanied by gelastic seizures the underlying lesion is most commonly located in the temporal cortex.     

Pediatric-onset gelastic seizures: clinical data and outcome

Gelastic seizures are an extremely rare form of epilepsy defined as automatic bouts of laughter without mirth commonly associated with a hypothalamic hamartoma. The objective was to survey all Israeli children found to develop recurrent gelastic seizures and report presenting symptoms, electroencephalographic and radiologic data, and response to either antiepileptic drugs or surgery. Ten children who developed gelastic seizures at the age of 1 week to 6.5 years (mean, 25 months) at a frequency from 3 bouts per week to >10 prolonged bouts per day were followed for a period of 1.3-12 years (mean, 6 years). Seven cases were defined as symptomatic: cortical magnetic resonance imaging revealed a hypothalamic hamartoma in four patients and cortical abnormalities in three others. Seizure control was achieved in four patients, including a neonate with status gelasticus and hypothalamic hamartoma, and partial control in one more. Five children remained resistant to polytherapy, including three with hypothalamic hamartoma even after two of them underwent hemartoma excision. Thus, children with gelastic seizures may respond relatively well to drug therapy. Four of the 10 patients became seizure free with drug therapy; in three intractable symptomatic cases, surgery was tried but failed in two of the three.     

Gelastic seizures and the anteromesial frontal lobe: A case report and review of intracranial EEG recording and electrocortical stimulation case studies

Symptomatogenic areas for ictal laughter have been described in the frontal and temporal lobes. Within the frontal lobe, gelastic seizures have been recorded from the cingulate gyrus. Electrocortical stimulation of the cingulate gyrus as well as the superior frontal gyrus induced laughter. We describe a patient whose gelastic seizures were associated with electrographic ictal activity in the mesial aspect of the right anterior frontal gyrus. The symptomatogenic area for ictal laughter in the frontal lobe may reside in the superior frontal gyrus.     

表现有立毛运动的复杂部分性癫痫(附3例报告及文献复习)

目的了解立毛运动性发作的病理生理、病因及临床特点。方法结合3例立毛运动性发作病例及文献复习(已报过21例)，探讨立毛运动性发作的特点。结果立毛运动性发作的最重要临床表现是反复的立毛运动，可能与右颞叶额叶(眶面皮层，运动前区)下丘脑和边缘系统学结构有关，脑电图(EEG)表现为非特异性异常，但是大多数病例有发作期发放或癫痫样波，视频监测脑电图(Video—EEG)对于评价其分型及发作期、发作间期变化有帮助。结论立毛运动性发作极罕见。但是注意结合病史，体检和EEG检查还是可以发现的。     

Gelastic seizure with tectal tumor, lobar holoprosencephaly, and subependymal nodules: clinical report

Gelastic seizures are characterized by inappropriate, stereotyped laughter and are often first recognized when other epileptic manifestations occur. They are frequently associated with hypothalamic hamartomas. Central nervous system developmental abnormalities are rarely reported with gelastic seizures. There is only one case report of gelastic seizure caused by holoprosencephaly. We report a 2-year-old girl with multiple brain structural abnormalities including tectal tumor (possibly hamartoma), multiple subependymal nodules, and holoprosencephaly. She developed seizures during the newborn period and presented with gelastic seizure and simple partial seizure at 3 months of age.     

Restricted frontomesial epileptogenic focus generating dyskinetic behavior and laughter

PURPOSE: Substantial data are missing about the anatomic location of frontal regions supporting gelastic seizures. METHODS: We report the results of stereo-electro-encephalographic recordings performed over several distinct functional premotor and executive fields in a patient whose seizures were characterized by dyskinetic behavior and ictal laughter, in the absence of cerebral MRI abnormalities. RESULTS: The epileptogenic zone was circumscribed in the anterior and ventral part of the supplementary motor area and the underlying dorsal cingulate cortex. There were no or little spreading to cortical neighboring areas. The patient is seizure-free (follow-up of 27 months) after a stereotactic electric radiofrequency lesion of the epileptogenic focus. CONCLUSION: The present data suggest that pericingulate premotor areas are involved in the triggering of the motor component of laughter. In this case, the coexistence of paroxysmal dyskinesias during laughter might reflect the involvement of specific compartment(s) of the basal ganglia.     

An unusual case of epilepsy exhibiting gelastic seizure, simple visual hallucination, and transient swelling of the left parieto-occipital region]

We report a 74-year-old man with gelastic seizure, simple visual hallucination, and adversive seizure. The patient described his visual hallucinations as "rotating light like a firefly" and "mimicking a stream". Brain CT scan showed a transient swelling as well as low density of a left parieto-occipital region. Electroencephalographic study revealed spikes and fast waves beginning at left occipital region. Although temporal lobe and hypothalamic lesions (especially hypothalamic hamartomas) are well known as origins of gelastic seizures, we could not find any report that described a series of occurrence of gelastic seizure and simple visual hallucination. Usually, simple visual hallucination is thought to occur in occipital lesion. In our case, it is possible that gelastic seizure and simple visual hallucination are related to the epileptic discharge from occipital lesion directly or indirectly. The reversible brain swelling with low density seen in the present case might be caused by cytotoxic edema due to status epilepticus.     

Cursive and gelastic manifestations of epilepsies

Seven cases of cursive and two cases of gelastic manifestations of epileptic seizures are presented. The cases were documented with computerized tomography and electroencephalography (EEG). Most of patients with cursive seizures showed temporal lobe epileptiform discharge in EEG. The authors discuss the theme in relation to pathophysiology and conclude that they are not a homogeneous group according to prognosis and nosology. Every case presented complex partial seizures with or without tonic-clonic seizures.     

A case of parietal lobe epilepsy with ictal laughter

We report here about an 8-year-old boy with parietal lobe epilepsy (PLE) and ictal laughter. At the age of 6, he began to experience drop seizures, followed by sensory fits. Interictal EEG showed frequent spikes at C3, C4, P3 and Cz. Despite treatment with antiepileptic drugs, he often fell down in seizures after feeling abnormal sensations in the right shoulder. On ictal video EEG at the age of 7 years, (1) he became motionless and complained of fear and pain in the right hand, (2) he had clonic seizures of the right upper limb and fell down to his left, (3) he laughed though he did not feel funny. Ictal EEG showed spikes which originated in Pz and then were generalized. In many of the previously reported cases, ictal laughter is associated with hypothalamic hamartomas, infantile spasms,. complex partial seizures of frontal, temporal, or parietal origin. We diagnosed the present case as having PLE. However, other localization could not be roled out because the spikes were generalized quickly. To date, there are two reported cases of ictal laughter with PLE, but ictal EEG is lacking in these patients. Ictal laughter is rare in non-lesional cryptogenic PLE, but it may imply PLE's pathogenesis.     

A note on gelastic epilepsy

Laughter epilepsy or gelastic seizures have been described in various epilepsies arising from the temporal or frontal lobes, but most commonly from hypothalamic hamartomata. Gelastic seizures also arise from temporal and frontal lobe tumours and atrophic lesions. The essential clinical features are: stereotyped recurrence; absence of external precipitants; concomitance of other manifestations generally accepted as epileptic; presence of interictal or interictal EEG epileptiform discharges, and absence of conditions in which pathological laughter might occur. The history and clinical significance are discussed.     

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.     

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.