Stereotactic Laser Ablation for Hypothalamic Hamartoma

Stereotactic laser ablation (SLA) is a minimally invasive approach to the treatment of medication-resistant epilepsy that accomplishes ablation of the seizure focus with real-time magnetic resonance thermal mapping. Rates of seizure freedom in early series suggest that SLA approaches and perhaps surpasses the effectiveness of open resection. SLA minimizes the neurocognitive and endocrine adverse effects of open surgery. Secondary benefits of SLA include decreased length of stay, elimination of intensive care unit stay, reduced procedure-related discomfort, and improved access to surgical treatment for patients less likely to consider an open resective procedure.

Key points

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Stereotactic laser ablation (SLA) is a minimally invasive approach to the treatment of medication-resistant epilepsy that accomplishes ablation of the seizure focus with real-time magnetic resonance thermal mapping.
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Rates of seizure freedom in early series suggest that SLA approaches and perhaps surpasses the effectiveness of open resection.
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SLA minimizes the neurocognitive and endocrine adverse effects of open surgery.
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Secondary benefits of SLA include decreased length of stay, elimination of intensive care unit stay, reduced procedure-related discomfort, and improved access to surgical treatment for patients less likely to consider an open resective procedure.

Introduction

Hypothalamic hamartomas (HHs) are non-neoplastic developmental malformations centered around the tuber cinereum. They are associated with medically refractory epilepsy, developmental delays, and often precocious puberty (up to 40% of cases). Pathologically, HHs are characterized by disorganized glioneuronal tissue, and can be readily divided into 2 types: sessile and pedunculated, with many other specific classifications also proposed, such as that by Delalande and Fohlen, which divides HHs into type I (within the tuber cinereum, usually eccentric to one side), type II (intraventricular), type III (mixed), and type IV (giant, >2 cm in diameter).

Gelastic seizures (GSs) are the first and most specific type of seizure experienced by patients with HHs. GSs vary from feeling a mild “pressure to laugh,” to uncontrollable outbursts of laughter, during which consciousness is usually maintained. These mechanical bursts of laughter are not experienced as mirthful, and are often associated with concomitant autonomic signs, such as mydriasis and facial flushing.

Up to 75% of patients with GSs go on to develop other types of intractable seizures, ranging from partial motor to generalized tonic-clonic. This secondary epileptogenesis is presumed due to the HH and resultant GSs, akin to a kindling effect. This same process also appears to drive the resultant encephalopathy responsible for behavioral, cognitive, and psychiatric impairments in patients with HH. Importantly, surgical ablation of the HH can reverse this encephalopathy, reducing the frequency of seizures and improving cognitive and behavioral functioning.

Many techniques have been used to remove and disconnect HHs, including open surgery, endoscopic approaches, stereotactic radiofrequency (RF) ablation, and stereotactic radiosurgery. Open surgical approaches include transcallosal (primarily for Delalande types II, III, and IV) and skull base approaches, such as orbitozygomatic or pterional craniotomies (primarily for types I, III, and IV). These procedures lead to seizure freedom in approximately 50% of patients, but have a high rate of complications, including transient memory disturbances in roughly half of the transcallosal patients and sporadic diabetes insipidus, poikilothermia, visual field deficits, and hemiparesis in the skull base patients.

Complete endoscopic resection of HHs is technically difficult: for example, Rekate and colleagues report a series of 44 patients, of whom they achieved total resection in just 14 (32%). The complication rate in this series was 25%, although most were transient. When resection fails, disconnection of the HH using endoscopic surgery is another option, and again leads to a roughly 50% rate of seizure freedom.

MRI-guided stereotactic RF ablation, although a more recent development, is a technically less-invasive technique than open surgery, with rates of seizure freedom approaching 75%, although it nevertheless harbors similar complications to open surgical procedures (memory loss, brainstem infarctions, and cranial nerve palsies).

Several methods of stereotactic radiosurgery have been used for HHs. Gamma Knife radiosurgery has been the most studied modality, and showed a 37% seizure freedom rate without permanent complications in the largest series to date (27 patients with adequate follow-up). Linear accelerators have shown less success, with 2 small reports showing no improvement, and 1 showing seizure freedom in 2 of 3 patients. All radiosurgery modalities take a substantial time period for effects to manifest, usually on the course of 1 to 2 years.

A more recent approach to the treatment of HHs is MRI-guided laser ablation. There has been only one study published to date using laser ablation, but the results were favorable, with 86% of 14 patients achieving complete seizure freedom, and an absence of any permanent side effects ( Table 1 ).

Table 1

Approaches to hypothalamic hamartoma

Technique	Pros	Cons
Open surgery • Endoscopic • Craniotomy	Direct visualization	• High risk for morbidity ○ Memory impairments ○ Endocrine dysfunction ○ General surgical (eg, infection, stroke)
Stereotactic radiosurgery (SRS)	Noninvasive	• Delayed benefit after initial increase in seizures (risk of sudden unexpected death in epilepsy with continued seizures) • Potential radiation injury, dose limitations • High cost
Laser interstitial thermal therapy (LITT)	Minimal collateral damage Immediate benefit Near real-time MR thermography guides therapy and confirms ablation zone	• High cost/disposables • Must be cleared for MRI (excluding patients with implantable devices)

Laser Interstitial Thermal Therapy

During laser interstitial thermal therapy (LITT), laser light is delivered fiberoptically into tissue (interstitial) via a stereotactic approach. Unlike RF ablation, LITT uses photonic energy for thermocoagulation. Several critical advances have made modern LITT platforms into elegant and powerful neurosurgical tools ( Box 1 ). The most critical advance is the ability to use MRI thermometry to measure not only the temperature at the device tip (the only temperature monitored in RF ablation), but also the temperature of tissue any distance from the tip during heating, thus providing near real-time confirmation of the ablation zone relative to off-target structures.

Box 1

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Optical fiber with diffusing tip (10 or 3 mm)
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Cooling cannula to control thermal spread within tissue and protect device tip
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984-nm diode laser causes rapid heating of water within tissue
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Magnetic resonance thermography reads temperature change in all voxels
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6 safety points to automatically shut off laser if temperature limits exceeded
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Irreversible damage zone estimate at each voxel based on Arrhenius equation

Laser interstitial thermal therapy

The photonic mechanism of heating is different from RF ablation, but the effects of temperature on tissue are the same. Although, again, thermometry allows monitoring of distal effects of heating, as compared with only tip measurements with radiofrequency probes. This technology allows protection of off-target tissue at risk in a way that is not possible with standard use of RF ablation. At present, 2 LITT devices are available in the United States that offer overlapping but distinctive features. Our study has used only the Visualase (Medtronic, Minneapolis, MN; Fig. 1 ).