Seizure outcome and prognostic factors for surgical management of hypothalamic hamartomas in children.

PURPOSE: Hypothalamic hamartomas (HH) are rare benign lesions frequently associated with gelastic seizures early in life. Epilepsy can progress to multiple seizure types with cognitive impairment and behavioural disturbance, leading in some cases to epileptic encephalopathy. METHODS: We reviewed a retrospective series of 112 children treated in a single center, between 1998 and 2017. RESULTS: According to Delalande's HH classification, type1 was found in 2 patients, type 2 in 67, type 3 in 31, and type 4 in 12 patients. Stereotactic endoscopic disconnection was performed in 92 % of the procedures. Median age at diagnosis was 40 months and 7.6 years at surgery. Median time between diagnosis and surgery was 31 months and median follow up 4.1 years. For all HH types, 77.6 % of the patients had a favourable outcome (Engel I + II outcome score) with 57.1 % seizure-free (Engel I). The best outcome was obtained in patients with type 2 HH, (68.7 % Engel I and 85.1 % Engel I + II). The overall complication rate was 8.3 %, which is in line with previous series. Patients with isolated gelastic seizures had a better outcome (Engel I + II in 90 %), as compared to those with other seizure types (p = 0.07). A short delay between hamartoma diagnosis and surgery was a statistically significant factor for a good outcome (p = 0.03). CONCLUSION: Patients with HH and drug-resistant epilepsy should be early identified in order to propose surgical treatment without delay. Endoscopic disconnection is a safe and efficacious surgical option with good seizure outcome and immediate treatment results.

Classification of hypothalamic hamartoma and prognostic factors for surgical outcome.

OBJECTIVES: The main aims of this study were to classify patients with hypothalamic hamartoma (HH) based on neuroimaging features and describe the clinical manifestations of HH. MATERIALS AND METHODS: A retrospective review of 214 consecutive patients with HH treated in Beijing Tiantan Hospital was performed. RESULTS: HH were diagnosed and divided into Types I-IV based on MRI. Types I and II were defined as the HH attached to the floor of the third ventricle with narrow (Type I) or broad (Type II) interfaces. Type III ('straddling') was defined by the HH extending into the third ventricle and interpeduncular cistern. Type IV was defined as the HH located totally within the third ventricle. The percent distribution of patients was 35.9% Type I, 12.1% Type II, 40.7% Type III, and 11.2% Type IV. The percentage of patients with precocious puberty was highest in Type I (81.8%). The percentage of patients with gelastic seizures was highest in Type IV (91.7%). After surgery, 20% (1/5) of patients with Type II HH, 48.8% (20/42) with Type III, and 91.7% (11/12) with Type IV were free of epileptic seizures. Significant prognostic factors for surgical outcome were HH size, surgical approach, and resection level. CONCLUSIONS: The clinical manifestations of HH are correlated with the topology of the HH in relation to the hypothalamus. Our results suggest that patients with Type IV HH have the best outcome from surgery and neurosurgeons should be cautious about performing surgery on patients with Type II and Type III HH.

Repeat surgery for hypothalamic hamartoma in refractory epilepsy.

OBJECT: Hypothalamic hamartomas (HHs) often cause pharmacoresistant epilepsy, incapacitating behavioral abnormalities, and cognitive decline. Surgical intervention offers the patient the best opportunity of seizure resolution, which occurs in approximately 50%­60% of patients, and improvement in both cognitive and behavioral difficulties. For those in whom the initial operation has failed, further medical treatment options remain quite limited, whereas, in some cases, a second surgery may improve seizure outcome. The authors retrospectively reviewed their surgical cases to document the success rate and complications of reoperations in patients with HHs. METHODS: Data were obtained from the HH epilepsy surgery database at the Barrow Neurological Institute between 2003 and 2010. Surgical treatment consisted of open and endoscopic procedures, as well as radiosurgery. Demographic details, seizure history, presurgical evaluation, and postoperative follow-up data were evaluated. RESULTS: In the last 7 years, 21 (13%) of 157 patients underwent reoperation after an initial epilepsy operation. The initial surgical approach in the 21 patients included: endoscopic (8 patients [38%]), transcallosal (8 patients [38%]), orbitozygomatic (3 patients [14%]), and radiosurgery (2 patients [10%]). Of the 8 patients who initially underwent endoscopic resection, repeat procedures included: radiosurgery in 4 (50%), an orbitozygomatic approach in 2 (25%), repeat endoscopy in 1 (12.5%), and a transcallosal approach in 1 (12.5%). Repeat procedures after an initial transcallosal resection included: endoscopic resection in 2 (25%); radiosurgery in 1 (12%); an orbitozygomatic approach in 2 (25%), and repeat transcallosal surgery in 3 (38%). Predominant seizure types that recurred after the first surgery were gelastic seizures, complex partial seizures, and tonic-clonic seizures. Magnetic resonance imaging in all patients prior to reoperation demonstrated either residual HH and/or connection with the mammillary bodies. Review of patients with more than 6 months of follow-up since the last surgery showed greater than 90% reduction in seizures in 4 patients (19%) and by 50%­90% in 10 patients (48%). Two patients were seizure free, and in 5 patients (24%) there was no change in seizure frequency. Following reoperation, none of the patients had any worsened behavioral issues such as increased rage attacks or disruptive violent behavior. New postoperative complications after reoperation included hemiparesis, thalamic stroke (asymptomatic and symptomatic), hyperphagia, and panhypopituitarism. CONCLUSIONS: Reoperation should be considered in selected patients with HH in whom initial epilepsy surgery fails because more than half the patients have significant reductions in seizure.

Epilepsy related to hypothalamic hamartomas: surgical management with special reference to gamma knife surgery.

OBJECTIVE: A large spectrum of surgical techniques can be proposed to young patients presenting with hypothalamic hamartomas (HH) associated with severe epilepsy. The aim of this report is to point on some clinical and anatomical parameters supposed to influence the choice of the surgical approach and to emphasize the specific role of radiosurgery. MATERIALS AND METHODS: We reviewed both our experience and the recent literature based on a Pubmed search. Lateral pterional, midline frontal through the lamina terminalis, transcallosal interforniceal approaches, endoscopic treatment through the foramen of Monro, disconnecting surgery, radiofrequency ablation, brachytherapy and gamma knife surgery (GKS) were all considered. Mortality, morbidity, and efficacy of each of these techniques were compared. Specific limits, difficulties, and constraints were taken into account. Our experience of radiosurgery is based on a prospective trial which enrolled 60 patients with HH and associated severe epilepsy between October 1999 and December 2005. RESULTS: Several surgical techniques can lead to a real reversal of the epileptic encephalopathy. The main factors for the decision-making process are the age, the size of the lesion and its anatomical type (according to our original classification), the severity of the epilepsy, and the severity of the cognitive/psychiatric comorbidity. In our prospective trial (GKS), 27 patients have a follow-up superior to 3 years. Among those, 59.2% have an excellent result with a dramatic behavioral and cognitive improvement and are completely seizure-free (37%) or have only rare non-disabling seizures (22.2%). No permanent neurological complication has been observed so far; three patients have presented a transient poïkilothermia. GKS is clearly the safer approach for these difficult patients. Young patients with severe epilepsy and comorbidity must be operated on using a curative approach as early as possible. Very large type VI or mixed type with a large component above the floor of the third ventricle must be disconnected and then the upper remnant can be ideally treated by GKS (staged surgery). Type V (rarely epileptic) and IV are frequently operable by disconnection. Type I HH deeply embedded in the hypothalamus are operated on by GKS efficiently and safely. Type II HH can be operated on either endoscopically or transcallosally or by GKS depending on the parents' choice and severity of epilepsy. In small type III HH, GKS is a safer procedure, due to the very close relationship to the fornix and mammillary bodies. In very large type III HH, transcallosal interforniceal approach is proposed but with significant risks especially concerning short-term memory. When the lesion is sufficiently small, GKS is globally offering the patient a rate of seizure cessation comparable to microsurgery with, however, a much lower risk (no neurological deficit reported till now). CONCLUSION: Our first results indicate that GKS is as effective as microsurgical resection and very much safer. GKS also allows avoiding the vascular risk related to radiofrequency lesioning or stimulation. The disadvantage of radiosurgery is its delayed action. Longer follow-up is mandatory for a reliable evaluation of the role of GKS. The early effect on subclinical discharges turns out to play a major role in the dramatic improvement of sleep quality, behavior, and developmental learning acceleration at school.

The relationship between magnetic resonance imaging findings and clinical manifestations of hypothalamic hamartoma.

OBJECT: Hypothalamic hamartoma is generally diagnosed based on its magnetic resonance (MR) imaging characteristics and the patient's clinical symptoms, but the relationship between the neuroradiological findings and clinical presentation has never been fully investigated. In this retrospective study the authors sought to determine this relationship. METHODS: The authors classified 11 cases of hypothalamic hamartoma into two categories based on the MR findings. Seven cases were the "parahypothalamic type," in which the hamartoma is only attached to the floor of the third ventricle or suspended from the floor by a peduncle. Four cases were the "intrahypothalamic type," in which the hamartoma involved or was enveloped by the hypothalamus and the tumor distorted the third ventricle. Six patients with the parahypothalamic type exhibited precocious puberty, which was controlled by a luteinizing hormone-releasing hormone analog, and one patient was asymptomatic. No seizures or mental retardation were observed in this group. All patients with the intrahypothalamic type had medically intractable seizures, and precocious puberty was seen in one. Severe mental retardation and behavioral disorders including aggressiveness were seen in two patients. The seizures were controlled in only one patient, in whom stereotactically targeted irradiation of the lesion was performed. This topology/symptom relationship was reconfirmed in a review of 61 reported cases of hamartoma, in which the MR findings were clearly described. The parahypothalamic type is generally associated with precocious puberty but is unaccompanied by seizures or developmental delay, whereas the intrahypothalamic type is generally associated with seizures. Two thirds of patients with the latter experience developmental delays, and half also exhibit precocious puberty. CONCLUSIONS: Classification of hypothalamic hamartomas into these two categories based on MR findings resulted in a clear correlation between symptoms and the subsequent clinical course.