White matter density is increased in patients with hypothalamic hamartoma and multiple seizure types

Many patients with hypothalamic hamartomas present in infancy with gelastic seizures of subcortical origin, but later develop additional seizure types, including complex partial, tonic, and generalized tonic-clonic seizures. The basic cellular mechanisms responsible for this evolution in seizure types are unknown. Using voxel-based morphometry of T1 weighted MRI scans we compared eight patients with only gelastic seizures with 16 age-matched patients with multiple seizure types and found significantly greater white matter density in the temporal lobes and cerebellum in those with multiple seizure types. This suggests that increased white matter density, perhaps resulting from maturational changes and resulting in increased brain connectivity, is associated with a higher likelihood of cortical involvement in epilepsy resulting from hypothalamic hamartoma.     

Gelastic seizures associated with hypothalamic hamartomas. An update in the clinical presentation,diagnosis and treatment

Gelastic seizures are epileptic events characterized by bouts of laughter. Laughter-like vocalization is usually combined with facial contraction in the form of a smile. Autonomic features such as flushing, tachycardia, and altered respiration are widely recognized. Conscious state may not be impaired, although this is often difficult to asses particularly in young children. Gelastic seizures have been associated classically to hypothalamic hamartomas, although different extrahypothalamic localizations have been described. Hypothalamic hamartomas are rare congenital lesions presenting with the classic triad of gelastic epilepsy, precocious puberty and developmental delay. The clinical course of patients with gelastic seizures associated with hypothalamic hamartomas is progressive, commencing with gelastic seizures in infancy, deteriorating into more complex seizure disorder resulting in intractable epilepsy. Electrophysiological, radiological, and pathophysiological studies have confirmed the intrinsic epileptogenicity of the hypothalamic hamartoma. Currently the most effective surgical approach is the trancallosal anterior interforniceal approach, however newer approaches including the endoscopic and other treatment such as radiosurgery and gamma knife have been used with success. This review focuses on the syndrome of gelastic seizures associated with hypothalamic hamartomas, but it also reviews other concepts such as status gelasticus and some aspects of gelastic seizures in other locations.     

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.     

Analysis of the EEG dynamics of epileptic activity in gelastic seizures using decomposition in independent components.

OBJECTIVE: Gelastic seizures are a frequent and well established manifestation of the epilepsy associated with hypothalamic hamartomas. The scalp EEG recordings very seldom demonstrate clear spike activity and the information about the ictal epilepsy dynamics is limited. In this work, we try to isolate epileptic rhythms in gelastic seizures and study their generators. METHODS: We extracted rhythmic activity from EEG scalp recordings of gelastic seizures using decomposition in independent components (ICA) in three patients, two with hypothalamic hamartomas and one with no hypothalamic lesion. Time analysis of these rhythms and inverse source analysis was done to recover their foci of origin and temporal dynamics. RESULTS: In the two patients with hypothalamic hamartomas consistent ictal delta (2-3 Hz) rhythms were present, with subcortical generators in both and a superficial one in a single patient. The latter pattern was observed in the patient with no hypothalamic hamartoma visible in MRI. The deep generators activated earlier than the superficial ones, suggesting a consistent sub-cortical origin of the rhythmical activity. CONCLUSIONS: Our data is compatible with early and brief epileptic generators in deep sub-cortical regions and more superficial ones activating later. SIGNIFICANCE: Gelastic seizures express rhythms on scalp EEG compatible with epileptic activity originating in sub-cortical generators and secondarily involving cortical ones.     

Hypothalamic hamartoma and seizures: a treatable epileptic encephalopathy

Hypothalamic hamartomas may be associated with gelastic seizures, focal seizures, and a generalized epileptic encephalopathy, with severe seizures and cognitive and behavior decline. Despite earlier views to the contrary, good evidence now exists that all these clinical features are caused, directly or indirectly, by the hamartoma. Resection of these lesions was long regarded as too hazardous and unlikely to benefit seizure control. It is now clear that hypothalamic hamartomas can be effectively treated with a variety of surgical approaches with sustained seizure control and often seizure freedom. Qualitative observations suggest that behavior and cognition also improve with treatment, but quantitative validation is required. The specific approach should be tailored according to the surgical anatomy of the lesion and the experience of the surgeon. Choices include a transcallosal approach (good for intraventricular lesions), a pterional approach (useful for interpeduncular lesions), a transventricular endoscopic approach, or destruction of the lesion with radiofrequency probes or gamma knife radiosurgery. The previously dismal outlook for children with severe seizures associated with this lesion has now dramatically changed. These insights may have implications for other epileptic encephalopathies of childhood.     

Emergency transcallosal resection of hypothalamic hamartoma for "status gelasticus"

Hypothalamic hamartomas are rare developmental malformations of the inferior hypothalamus. Typically they result in symptomatic, refractory mixed seizure disorder with trademark gelastic or laughing seizures. We present a 30-month-old boy with a hypothalamic hamartoma and a nearly 2-month history of near-continuous gelastic seizures, which we have labeled "status gelasticus." The seizures were refractory to multiple antiepileptic drugs (AEDs), and emergency transcallosal resection of the hypothalamic hamartoma was performed with resultant near-immediate cessation of the seizures. At 12-month follow-up, the patient was averaging one brief gelastic seizure every 2 weeks, with a longest seizure-free period of 2 months.     

立体定向射频毁损治疗表现为痴笑性癫癎的下丘脑错构瘤

目的总结采用立体定向热凝毁损手术方法治疗引起痴笑性癫癎的下丘脑微小错构瘤的经验。方法报告1例病人,男性,22岁,表现为痴笑性癫癎21年,继发复杂部分性发作7年,发作3～4次/d,药物治疗无效。MRI诊断为第三脑室内错构瘤,大小6mm×6mm×7mm。局麻下采用有框架立体定向技术,在病变内插入深部电极,记录并刺激后行射频毁损,制作4个靶点。结果深部电极在病灶内记录到棘波和慢波,刺激未诱发出痴笑性癫癎。术中行可逆毁损（45℃）和毁损（70℃）时,病人出现一过性中枢性高热、高血压和心动过速。术后随访6个月,痴笑性癫癎和复杂部分性发作完全消失,无手术并发症发生。结论下丘脑受到直接热刺激时可产生中枢性高热。对于较小的下丘脑错构瘤,立体定向热凝毁损术是一种安全有效的手术方法。     

立体定向射频毁损治疗下丘脑错构瘤伴癫痫病例报导并文献复习

目的 总结立体定向射频毁损手术方法,治疗下丘脑错构瘤伴癫痫的临床疗效,并分析毁损靶点位置的选择.方法 回顾性分析1例下丘脑错构瘤伴癫痫患者临床资料,并复习文献.患者女性,9岁,痴笑癫痫8年,继发复杂部分性发作3年,MRI提示下丘脑错构瘤.局麻下行立体定向射频毁损手术.结果 术后一周有尿量增多,无其它手术并发症.术后痴笑发作消失,复杂部分性发作减少.结论 立体定向射频毁损手术对于下丘脑错构瘤伴癫痫是一种安全有效的治疗方法,毁损靶点定位应包括错构瘤中心及错构瘤边缘乳头体丘脑束部位.     

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.     

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.     

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.     

The hypothalamic hamartoma: a model of subcortical epileptogenesis and encephalopathy

Although uncommon, the hypothalamic hamartoma (HH) is often associated with a devastating clinical syndrome, which may include refractory epilepsy, progressive cognitive decline, and deterioration in behavioral and psychiatric functioning. Contrary to conventional thinking which attributed seizure origin to cortical structures, the hamartoma itself has now been firmly established as the site of intrinsic epileptogenesis for the gelastic seizures (i.e., characterized by unusual mirth) peculiar to this disorder. It also appears that the HH contributes to a process of secondary epileptogenesis, with eventual cortical seizure onset of multiple types in some patients. Anticonvulsant medications are known to be poorly effective in this disorder. Treatment, including some innovative approaches to surgical resection, is now targeted directly at the HH itself, with impressive results. Younger patients, in particular, may avoid the deteriorating course described earlier. Access to tissue from larger numbers of patients at single or collaborating centers specializing in HH surgery will allow for research into the fundamental mechanisms producing this little understood disorder. Refractory epilepsy associated with HH is the premier human model for subcortical epilepsy and an excellent model for secondary epileptogenesis and epileptic encephalopathy.     

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。     

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.     

Stereotactic radiofrequency thermocoagulation for hypothalamic hamartoma with intractable gelastic seizures

Management of hypothalamic hamartoma with intractable gelastic epilepsy remains controversial. We have used stereotactic thermocoagulation for treatment of hypothalamic hamartoma with intractable gelastic epilepsy since 1997. Herein, we review our experience in five cases to clarify the usefulness of this treatment. A total of five patients with hypothalamic hamartoma were treated by stereotactic thermocoagulation at our hospital during the period October 1997 through February 2004. In all patients, the hamartoma was less than 10mm in diameter and was located on the floor of the third ventricle with sessile attachment to the wall. To identify ictal onset, chronic intracranial electroencephalography was performed in three patients with the use of a depth electrode implanted in the hamartoma. Attempts were made to induce gelastic seizure by electrical stimulation of the hamartoma in three patients. After magnetic resonance imaging-guided targeting, radiofrequency thermocoagulation of the boundary between the hamartoma and normal hypothalamus was performed to achieve disconnection effects. Marked reductions in seizure frequency were obtained in all cases, with three patients becoming seizure-free after the procedure. No intraoperative complications occurred except in one patient who experienced acute and transient panidrosis with hot flushes during coagulation. Our results suggest that stereotactic thermocoagulation of hypothalamic hamartoma is an acceptable treatment option for patients with intractable gelastic seizures.     

Positron emission tomography with glucose hypermetabolism of a hypothalamic hamartoma in infantile spasms associated with Pallister–Hall syndrome

Although hypothalamic hamartomas (HHs) have been shown to be intrinsically epileptogenic and to participate in the generation of gelastic seizures, no evidence has been reported regarding its contribution to the pathogenesis of infantile spasms. We describe a male infant with Pallister–Hall syndrome who had a large HH presenting with infantile spasms without hypsarrhythmia. [¹⁸F]fluoro-deoxyglucose positron emission tomography scan performed during the period of epileptic spasms demonstrated glucose hypermetabolism of the HH, which resolved after cessation of the spasms with adrenocorticotropin hormone treatment. No concurrent increased metabolic activity in the lenticular nuclei or brainstem was observed in the ictal or interictal states. The present case suggests that HHs may be involved in the pathogenesis of infantile spasms, possibly with propagation of epileptic discharges from the hamartoma to the descending spinal pathway.     

Psychogenic gelastic seizures in a patient with hypothalamic hamartoma

Gelastic seizures are classically associated with hypothalamic hamartoma. The most effective treatment for gelastic epilepsy is surgery, although confirming that a hypothalamic hamartoma is an epileptic lesion prior to surgical intervention is challenging. Here, we report the case of a patient with a hypothalamic hamartoma who was diagnosed with psychogenic non-epileptic gelastic seizures using video-EEG monitoring. [Published with video sequences].     

A case of hypothalamic hamartoma with refractory seizures: successful treatment with gamma knife surgery

Hypothalamic hamartomas are associated with precocious puberty and gelastic epilepsy. The seizures are often refractory to antiepileptic medications. The treatment of hamartoma is not well established. We report a 3-year-6-month-old boy was admitted because of intractable seizures occurring several times a day. The findings on magnetic resonance imaging and his characteristic seizure led to the diagnosis of hypothalamic hamartoma. The seizures were resistant to multiple antiepileptic drugs, and persisted for about 3 years, during which his cognition deteriorated. Focal radiosurgery by a gamma knife of the hamartoma successfully controlled the seizures with no neurological complications, and his mental function improved.     

Gelastic seizures involving the right parietal lobe.

Gelastic seizures have been described in various epilepsies arising from the temporal or frontal lobes, although the most commonly encountered form is related to the presence of an hypothalamic hamartoma. We report a patient with gelastic seizures involving the right parietal lobe. Our patient, a 32-year-old man, underwent video-EEG monitoring, interictal and ictal brain SPECTs during gelastic seizures. Subtraction ictal SPECT co-registered to MRI (SISCOM), was performed to localize any ictal hyperperfusion during these gelastic seizures. The seizures consisted of brief staring followed by smiling and laughing. Electroencephalography during the gelastic seizures showed rhythmic sharp waves in the right parietal lobe. SISCOM showed ictal hyperperfusion in the right parietal lobe and medial portions of right cerebellum. Our findings suggest that the right parietal lobe may actively participate in the particular epileptogenic network generating gelastic seizures.     

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.