Recent advance in mechanism of epilepsy induced by hypothalamic hamartoma / 中华神经医学杂志

Hypothalamic hamartoma is a rare congenital malformation that can cause precocious puberty, epilepsy, cognitive behavior and mental disorders. Hypothalamic hamartoma is the best in vivo model for studying subcortical epilepsy in human. The eplieptogenesis of hypothalamic hamartoma has already been highlight in epilepotology. With deeply exploring and revealing its intrinsic eplieptogenesis of hypothalamic hamartoma, it can expand our research views and ultimately bring new therapies to patients. The latest research progress on epilepotology induced by hypothalamic hamartoma is reviewed as follows.

Clinical Manifestations and Treatment of Hypothalamic Hamartoma

PURPOSE: The aim of this study was to describe the clinical manifestations and radiologic characteristics of patients with hypothalamic hamartoma (HH) and to delineate various treatment modalities.METHODS: We retrospectively reviewed the medical records of 11 patients with HH at Samsung Seoul Hospital between 1997 and 2013.RESULTS: Mean age of diagnosis was 2.7 years. Seven patients had intractable epilepsy, seven exhibited precocious puberty, and four had both. Gelastic seizure was the most common seizure and was intractable to medications. The patients with the intrahypothalamic type (18.2%) had no precocious puberty, while those with the parahypothalamic type (36.4%) didn't have seizures. Patients (n=6) with intractable epilepsy underwent gamma-knife radiosurgery (GKS); five of these patients responded to this treatment.CONCLUSIONS: The most frequent presenting symptoms of HH were gelastic seizure and precocious puberty. The location and size of tumor defined by brain magnetic resonance imaging affected presenting symptoms and the selection of surgical treatment. GKS can be considered if the patients showed intractable epilepsy and the size of tumor is less than 2 cm in diameter.

Clinical Manifestations and Treatment of Hypothalamic Hamartoma / 대한간질학회지

PURPOSE: The aim of this study was to describe the clinical manifestations and radiologic characteristics of patients with hypothalamic hamartoma (HH) and to delineate various treatment modalities. METHODS: We retrospectively reviewed the medical records of 11 patients with HH at Samsung Seoul Hospital between 1997 and 2013. RESULTS: Mean age of diagnosis was 2.7 years. Seven patients had intractable epilepsy, seven exhibited precocious puberty, and four had both. Gelastic seizure was the most common seizure and was intractable to medications. The patients with the intrahypothalamic type (18.2%) had no precocious puberty, while those with the parahypothalamic type (36.4%) didn't have seizures. Patients (n=6) with intractable epilepsy underwent gamma-knife radiosurgery (GKS); five of these patients responded to this treatment. CONCLUSIONS: The most frequent presenting symptoms of HH were gelastic seizure and precocious puberty. The location and size of tumor defined by brain magnetic resonance imaging affected presenting symptoms and the selection of surgical treatment. GKS can be considered if the patients showed intractable epilepsy and the size of tumor is less than 2 cm in diameter.

Current Source Analysis of Interictal Spikes in Two Patients With Gelastic Epilepsy-Hypothalamic Hamartoma Syndrome

BACKGROUND: Interictal spikes in gelastic epilepsy-hypothalamic hamartoma syndrome are mainly in the fronto-temporal area. Current source analysis of the interictal spikes has not been done enough. We tried the current source analysis in 2 patients with gelastic epilepsy-hypothalamic hamartoma syndrome using both of the discrete and distributed models. METHODS: Twenty 1 sec epochs including the negative peak of the spikes, were selected from one or two electroencephalographic recordings respectively in each patient. These 20 epochs were averaged into a single spike. The current dipole sources of the averaged spike were analyzed and located on a spherical head model. The current source density of the negative peak point of the averaged spike was located on the Talairach human brain map. RESULTS: The current dipole sources were in the right subcallosal gyrus, or the right or left anterior cingulate gyri. The current source density was distributed in the bilateral medial frontal area including the anterior cingulate gyri. CONCLUSIONS: The interictal spikes of patients with gelastic epilepsy-hypothalamic hamartoma syndrome may be generated by the current sources located in the bilateral medial frontal area.

Gamma Knife Radiosurgery in Patients with a Hypothalamic Hamartoma Associated with Intractable Gelastic Epilepsy: Report of Three Cases

Hypothalamic hamartoma(HH) is an unusual nonneoplastic developmental lesion associated with gelastic epilepsy and precocious puberty, mostly found in children. Although open surgery has been attempted when antiepileptic medication failed to control seizures, its deep location and surrounding vital structures often rendered surgery unsuccessful. We describe the outcome of gamma knife radiosurgery in three children with a HH associated with gelastic epilepsy and reviewed the literature for a possible therapeutic mechanism.

Gelastic Seizure with Ataxic Hemiparesis Following Aseptic Meningitis / 대한소아신경학회지

Gelastic seizure(ictal laughter) is quite rare and associated with variable etiologies. The relationship between infection and gelastic seizure is not clear. The seizure usually begins in infancy or childhood and may be accompanied with precocious puberty and cognitive decline. It is known to be poorly responded to medical or surgical treatments. A 5-year-old boy diagnosed and aseptic meningitis visited our hospital again twenty days later because of paroxysmal and frequent involuntary laughing regardless of emotional changes, left side dominant muscle weakness and ataxia with gait disturbance for 5 days. Initial brain magnetic resonance image(MRI) showed no abnormalities but follow-up MRI taken twenty days later showed high signal intensity on right thalamus. The interictal electroencephalogram(EEG) revealed multiple polyspikes over the frontal area. Other etiologies could not be documented. It was suspected that previous aseptic meningitis resulted in gelastic seizure with ataxic hemiparesis. After medical treatment, he acquired good outcomes with a seizure free state.

Gamma knife radiosurgery for hypothalamic hamartomas / 第三军医大学学报

Objective To investigate the treatment effect of gamma knife radiosurgery for hypothalamic hamartomas. Methods Gamma knife radiosurgery was performed in 9 patients with gelastic seizures. Collimator helmets (4 and 8 mm) were used and a radiosurgery plan was designed to cover 90% of the hamartoma at the 40%~55% isodose curve with the center dose of 28~40 Gy and the margin dose of 12~18 Gy. The clinical outcome was evaluated with the Tan’s scale. Results No complications due to gamma knife radiosurgery occurred. A follow-up from 24 to 54 months showed effectiveness in 7 patients, disappearance of seizure in 1 patient, rare occurrence in 3 patients, significantly reduced occurrence in 2 patients, improvement in seizure control in 1 patient, but ineffectiveness in 2 patients. Conclusion As an approach to the treatment of hypothalamic hamartomas, gamma knife is a safe and cost-effective therapy with rare side effects for hypothalamic harmatomas.

An Experience of Gamma Knife Radiosurgery for Hypothalamic Hamartoma with Gelastic Seizure / 대한간질학회지

We report a 12 year-old girl patient with hypothalmic hamartoma presented a gelastic seizure for 11 years. On magnetic resonance images, a 10.5 mm-sized mass was detected that was originated from the tuber cinereum into the third ventricle. This mass was isosignal intensity on T1WI, slightly high signal intensity on T2WI and not enhanced with Gadolinium. On interictal EEG, the frequent spike or polyspike dischage was recorded from the left fronto-central area. On ictal EEG, the suspicious polyspike dischages followed by spike and wave discharge were recorded from the left or both fronto-central or fronto-centro-temporal area. On 18-FDG PET (18-fluorodeoxyglucose positron emission tomography), the glucose metabolism was decresed on the mass. We treated this lesion using gamma knife radiosurgery (18 Gy at 50% margin, 508.2 mm3 volume). After 6 months, the frequency of gelastic seizure was decreased.

A Case of Spinal Epidural Hematoma due to Arteriovenous Malformation

Spinal epidural hematoma results from various causes such as use of anticoagulants, hemorrhagic diathesis, pregnancy, labor, arteriovenous malformation and spinal anesthesia as well as idiopathic orgin. We report a 3-year-old boy who was found to have spinal epidural hematoma and presented with lower back pain and fever. He developed paraplegia of lower legs after two consecutive lumbar punctures during two days. The lesion of spinal epidural hematoma was not found with lumbar spinal MRI but with cervico-thorasic one, because the lesion was at the C7-T6 level. Laminectomy was done to evacuate the hematoma and some specimen was obtained, of which pathologic finding was arteriovenous malformation. The boy is receiving physical therapy continuously due to unsatisfactory results with hematoma aspiration procedure and laminectomy treatment.

Treatment of Hypothalamic Hamartoma

This study presents seven patients with hypothalamic hamartomas diagnosed on the basis of MRI. Histological confirmation was performed in one patient who underwent surgery. Four patients presented with epilepsy, including gelastic seizures. Other symptoms were behavior abnormalities in 3 patients and precocious puberty in 4 patients. We classify hypothalamic hamartomas into four subgroups according to MRI finding: Types la lesions were less than 100mm in lesions less than 10mm and mammillary body. Type lla lesions were more than 100mm in diamenter and sessilely attached to hypothalamus with slight hypothalmic displacement and Type llb lesions more than 10mm and with marked displacement of hypothalamus. We could achieve good result with surgical resection in one patient with Type llb hamartoma associated with gelastic seizure that was unresponsive to medical treatment. We performed gamma knife radiosurgery in three patients with gelastic seizue(2 patients with Type lla and 1 patient with Type llb) and three patients with precocious puberty(2 patients with Type la and 1 patient with Type lla 1 patient with Type llb) and three patients with precocious puberty(2 patients with Type la and 1 patient with type lb). The authors propose direct surgery as a treatment for this progressive syndrome and gamma knife radiourgery is alternative treatment for high risk patients.

Hypothalamic Tumors Causing Precocious Puberty

Various types CNS lesions bring about precocious puberty and mostly these lesions involve the hypothalamus. We experienced two cases of hypothalamic hamartomas and a case of hypothalamic astrocytoma, presenting sexual precocity as the initial symptom. Other clinical findings included gelastic seizure, behavioral disturbance, accelerated bony growth. MRI of the hamartoma showed high signal intensities on T2 weighted spin echo image. The two hypothalamic hamartomas were partially removed and the patients showed some improvements endocrinologically and clinically one month after the operation. Literatures about the hypothalamic hemartoma were reviewed and the problems especially in the extent of surgical removal in the hypothalamic hamartomas were discussed.