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.     

Cognitive deficits in children with gelastic seizures and hypothalamic hamartoma.

OBJECTIVE: To characterize the cognitive deficits in children with gelastic seizures and hypothalamic hamartoma and investigate the relationship of seizure severity to cognitive abilities. METHODS: Eight children with gelastic seizures and hypothalamic hamartoma completed a neuropsychological battery of standardized and age-normed tests, including the Woodcock-Johnson Psycho-Educational Battery-Revised: Tests of Cognitive Ability, Peabody Picture Vocabulary Test-III, and initial-letter word fluency measure. RESULTS: All children displayed cognitive deficits, ranging from mild to severe. Gelastic/complex partial seizure severity was correlated with broad cognitive ability standard scores (r = -0.79; r2 = 0.63; (F[1,6] = 10.28; p = 0.018]. Frequency of gelastic/complex partial seizures was also correlated with broad cognitive ability standard scores (r = -0.72; r2 = 0.52; F[1,6] = 6.44; p = 0.044). Significant intracognitive standard score differences were found, with relative weaknesses in long-term retrieval (mean = 64.1; SD = 13.3) and processing speed (mean = 67.7; SD = 21.6) and a relative strength in visual processing (mean = 97.6; SD = 12.8). Performance in visual processing differed from performance in long-term retrieval (p = 0.009) and processing speed (p = 0.029). CONCLUSION: These findings are consistent with cognitive functions and affective/emotional states associated with conduction pathways of the hypothalamus involving cortical association areas and amygdala and hippocampal formation. These abnormalities can account for the prominent deficit found in integrating information in the processing of memories.     

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.     

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]     

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.     

Gelastic seizures treated by resection of a hypothalamic hamartoma

A 7-year-old girl presented for evaluation of a peculiar kind of epilepsy. Her seizures began before 1 year of age and consisted of episodes of brief, uncontrolled and unprovoked laughter than with time progressed to include cursive, complex partial and generalized tonic-clonic seizures. Progressive impairment of cognitive functions was noted as well as precocious puberty. Neuroimaging examination disclosed a hypothalamic hamartoma. It was excised by a pterional approach, and no further seizures were noted. The authors propose direct surgery for the hypothalamic hamartoma as a treatment for this progressive syndrome.     

Surgical treatment of extra‐hypothalamic epilepsies presenting with gelastic seizures

We provide an overview of the surgical outcome of extra‐hypothalamic epilepsies with gelastic seizures based on an original case report and a summary of the literature. Twenty‐two articles providing information on the outcome of resective surgery in 39 patients with extra‐hypothalamic gelastic seizures from the temporal (19 patients) or frontal lobe (20 patients) were selected. We add another case of temporal lobe gelastic seizures to the literature with a video demonstrating the mirthful component of this patient's laughing seizures. Drug‐refractory cases of gelastic seizures from the temporal or frontal lobes are amenable to surgical treatment following thorough investigation with imaging, as well as scalp and intracranial EEG.     

Treatment options for gelastic epilepsy due to hypothalamic hamartoma: interstitial radiosurgery

Surgical treatment of hypothalamic hamartomas (HHs) as the underlying etiology of gelastic epilepsy is associated with a high risk of complications because of the close vicinity of adjacent structures such as the optic tracts and mammillary bodies. Treatment with interstitial radiosurgery uses stereotactically implanted (125)I seeds emitting gamma radiation from the center of the lesion, with a steep spatial gradient, over a period of about 3 weeks. This form of HH therapy offers particular advantages regarding the risk for major side effects. In a series of 15 children and adolescents treated in Freiburg, Germany, 53% of patients achieved significant improvement in seizure frequency (Engel class I or II outcome). Transient side effects were related to the development of local edema, resulting in headache and mental slowing. A persistent weight gain was noted in 3 patients, which was severe in 1 (20 kg). There were no other neurologic, neuropsychologic, or neuropsychiatric side effects, which compares favorably with most surgical series.     

Giant hypothalamic hamartoma and dacrystic seizures.

Ictal crying is a rare type of epileptic seizure associated with hypothalamic hamartoma and with other lesions such as tumours, vascular malformations, hippocampal sclerosis, or cerebral infarction. We describe the case of an infant with gelastic, dacrystic and other types of seizures associated with a giant hypothalamic hamartoma, and present a video sequence of dacrystic seizures. Dacrystic episodes presented in clusters at sleep onset, initially in the form of moaning followed by face-flushing that rapidly evolved to crying, associated with a lateral and upper deviation of both eyeballs, along with clonic aspects of the eyelids. After a few seconds, the crying became less intense, she stared, and oro-alimentary automatisms became prominent along with some slow horizontal movements of the eyes and the head. Following surgery, at the age of nine months, the gelastic seizures stopped, but dacrystic seizures persisted. [Published with video sequences].     

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.     

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.     

Gelastic seizures: not always hypothalamic hamartoma.

Gelastic seizures are often associated with hypothalamic hamartomas. However, focal cortical dysplasias can also cause "laughing seizures", and such cases can be difficult to localize with EEG. This case report presents a 29-year-old woman who was successfully rendered free of gelastic seizures after resection of a frontal cortical dysplasia, localized through MRI and SPECT imaging.[Published with video sequences].     

The syndrome gelastic seizures–hypothalamic hamartoma: Severe, potentially reversible encephalopathy

Hypothalamic hamartoma (HH) is the pathologic hallmark of a spectrum of epileptic conditions, ranging from a mild form of epilepsy, whose seizures are an urge to laugh without cognitive defects, to the fully developed syndrome of early onset gelastic seizures (GS) associated with precocious puberty and the evolution to a catastrophic epilepsy syndrome. However, a refractory focal or generalized epilepsy develops during the clinical course in nearly all cases. Neurophysiologic and neuroimaging studies have assessed the role of HH in the generation of the GS as well as in the process of secondary epileptogenesis. Electrophysiologic properties of small γ-aminobutyric acid (GABA)ergic, spontaneously firing neurons might explain the intrinsic epileptogenicity of HH. Surgical ablation of the HH can reverse both epilepsy and encephalopathy. Gamma-knife radiosurgery and image-guided robotic radiosurgery can be useful and safe approaches for treatment, in particular of small HH.     

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.     

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.