ABSTRACT
Hypothalamic hamartoma (HH) can be associated with a wide spectrum of epileptic conditions, ranging from a mild form with seizures characterized by urge to laugh and no cognitive involvement up to a catastrophic encephalopathy with early onset gelastic seizures (GS), precocious puberty, and mental retardation. Moreover, a refractory, either focal or generalized, epilepsy develops during the clinical course in nearly all the cases. Neurophysiologic and neuroimaging studies have demonstrated that HH itself generates GS and starts a process of secondary epileptogenesis responsible for refractory focal or generalized epilepsy. The intrinsic epileptogenicity of HH may be explained by the neurophysiological properties of small GABAergic, spontaneously firing HH neurons. Surgical ablation of HH can reverse epilepsy and encephalopathy. Gamma-knife radiosurgery and image-guided robotic radiosurgery seem to be useful and safe approaches for treatment, in particular of small HH. Here, we review this topic, based on literature reports and our personal observations. In addition, we discuss pathogenetic hypotheses and suggest new approaches to this intriguing issue.
Subject(s)
Epilepsies, Partial/complications , Hamartoma/complications , Hypothalamic Diseases/complications , Adolescent , Adult , Electroencephalography , Epilepsies, Partial/radiotherapy , Epilepsies, Partial/surgery , Female , Hamartoma/radiotherapy , Hamartoma/surgery , Humans , Hypothalamic Diseases/radiotherapy , Hypothalamic Diseases/surgery , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Middle Aged , Radiosurgery , Radiotherapy , Young AdultABSTRACT
BACKGROUND: Gelastic epilepsy due to hypothalamic hamartomas is usually a severe condition encompassing both epileptic seizures and an epileptic encephalopathy associated with behavioral and cognitive impairments. Here we report the effects of interstitial radiosurgery in the treatment of this generally pharmacoresistant epilepsy syndrome. METHODS: Twenty-four consecutive patients (3-46 years of age, 7 women, mean age 21.9 years, mean duration of epilepsy 17.6 years) with gelastic epilepsy due to MR-ascertained hypothalamic hamartoma and a minimum follow-up period of 1 year were included in this evaluation. Treatment was performed by interstitial radiosurgery using stereotactically implanted (125)I seeds. Effects of treatment on seizure frequency and possible side effects were assessed prospectively. Factors influencing outcome and side effects were analyzed statistically. RESULTS: After a mean 24-month follow-up period following the last radiosurgical treatment, 11/24 patients were seizure free or had seizure reduction of at least 90% (Engel class I and II), in some cases only after repeated treatment. The duration of epilepsy prior to radiosurgery negatively influenced outcome. Treatment was well tolerated in most patients. Headache, fatigue, and lethargy were transient side effects associated with the development of brain edema extending from the implantation site in five patients. Four patients had a weight gain of more than 5 kg which was severe in two patients. The majority of those patients whose cognitive functions initially deteriorated showed subsequent recovery of cognitive functions, but episodic memory in two patients showed persistent decline at 1 year follow-up. Longer disease duration increased the risk for cognitive side effects, and larger hamartoma size and eccentric seed positioning increased the risk for radiogenic brain edema. Neither perioperative mortality nor neurologic impairments, visual field defects, or endocrinologic disturbances were encountered following treatment. CONCLUSION: Interstitial radiosurgery was efficacious in significantly improving gelastic epilepsy in about half of the patients treated in this series. Weight gain may occur as a side effect, whereas other severe side effects reported following microsurgical removal of the hamartoma were absent. The study results strongly suggest early causal treatment, as chances for seizure control are higher and the risk for cognitive side effects is lower in patients with shorter disease duration.
Subject(s)
Brachytherapy/methods , Brachytherapy/statistics & numerical data , Epilepsies, Partial/radiotherapy , Hamartoma/radiotherapy , Hypothalamic Diseases/radiotherapy , Adolescent , Adult , Brachytherapy/adverse effects , Brain Edema/etiology , Brain Edema/physiopathology , Child , Child, Preschool , Cognition Disorders/etiology , Cognition Disorders/physiopathology , Cognition Disorders/therapy , Cohort Studies , Epilepsies, Partial/etiology , Epilepsies, Partial/physiopathology , Female , Follow-Up Studies , Hamartoma/complications , Hamartoma/pathology , Headache/etiology , Headache/physiopathology , Humans , Hypothalamic Diseases/complications , Hypothalamic Diseases/pathology , Hypothalamus/pathology , Hypothalamus/physiopathology , Hypothalamus/radiation effects , Iodine Radioisotopes/therapeutic use , Lethargy/etiology , Lethargy/physiopathology , Magnetic Resonance Imaging , Male , Middle Aged , Recovery of Function/physiology , Recovery of Function/radiation effects , Stereotaxic Techniques , Treatment Outcome , Weight Gain/physiology , Weight Gain/radiation effectsABSTRACT
The authors evaluated a new stereotactic radiosurgical approach in seven patients with gelastic epilepsy due to hypothalamic hamartomas. Stereotactic implantation of 125I-seeds into the hamartoma was feasible in six patients. At follow-up at least 1 year after interstitial radiotherapy, two patients had become seizure-free within 2 months, and two others had only persisting auras. There were no major perioperative or postoperative side effects.
Subject(s)
Brachytherapy/methods , Epilepsies, Partial/surgery , Hamartoma/surgery , Hypothalamic Diseases/surgery , Iodine Radioisotopes/therapeutic use , Radiosurgery , Adolescent , Adult , Child , Drug Implants , Drug Resistance , Epilepsies, Partial/etiology , Epilepsies, Partial/radiotherapy , Female , Follow-Up Studies , Hamartoma/complications , Hamartoma/radiotherapy , Humans , Hypothalamic Diseases/complications , Hypothalamic Diseases/radiotherapy , Iodine Radioisotopes/administration & dosage , Male , Radiosurgery/methods , Treatment OutcomeSubject(s)
Epilepsies, Partial/radiotherapy , Epilepsy, Absence/radiotherapy , Epilepsy, Complex Partial/radiotherapy , Epilepsy, Tonic-Clonic/radiotherapy , Phosphorus Radioisotopes/administration & dosage , Adolescent , Adult , Chronic Disease , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Radiotherapy Dosage , Remission Induction , Time FactorsABSTRACT
Focal irradiation of epileptic foci has been performed in a group of 6 epileptic patients, of whom 2 presented with epilepsy and 4 with epileptic psychoses. The epileptic focus was localized by means of conventional scalp EEG, electrocorticography and stereoelectroencephalography. Radiosurgery was performed by coupling a stereoguide to a 60Co unit using a 10-mm diameter collimator. An estimated dose of 10 Gy was administered. Results are presented and the mechanism of action of radiation discussed.
Subject(s)
Epilepsies, Partial/radiotherapy , Adolescent , Adult , Cobalt Radioisotopes/therapeutic use , Electroencephalography , Evoked Potentials/radiation effects , Female , Humans , Male , Neurocognitive Disorders/therapy , Tomography, X-Ray ComputedABSTRACT
Reconciling the early promising results of radiation therapy in the treatment of epilepsy with the recent theory concerning the role of nonsynaptic mechanisms in focal epileptogenesis, it is suggested that the potential of irradiation as an alternative to temporal lobe resection in intractable epilepsy should be re-evaluated.
