14 Hypothalamic Hamartomas
14.1 Introduction
Hypothalamic hamartomas (HH) are non-neoplastic gray matter lesions, generally occurring within or below the third ventricle. Patients most commonly present with gelastic seizures and precocious puberty. There has been some correlation between lesion location and presenting symptoms, as lesions within the third ventricle are more likely to cause epilepsy.1 The majority of cases are identified in childhood. Careful history often reveals that the symptoms have been present since an early age, sometimes since birth. Lesions are infrequently large enough to cause mass effect on adjacent structures or cerebrospinal fluid obstruction. Since they are hamartomas, they do not grow disproportionately to the brain over time.
14.2 Pathophysiology
Hypothalamic hamartoma tissue is inherently epileptogenic. Intraoperative recordings as well as single-cell in vitro recordings have demonstrated spontaneous firing from hamartoma neurons.2 The particular type of seizures generated by this tissue are called gelastic, and they respond poorly to medical therapy. The location of the attachment of the HH will determine symptomatology. They have been found within the third ventricle, occupying the floor of the third ventricle, and attached along the hypothalamic infundibulum. In large lesions, it may be difficult to determine the site of attachment, or they may appear attached to multiple regions. Lesions with purely infundibular attachments are more likely to result in precocious puberty than epilepsy. The particular interaction between hamartoma cells and cells of the hypophyseal system is not well understood.
14.3 Clinical Features
Gelastic epilepsy is the most common presenting symptom. The semiology most often involves laughter that is inappropriate, uncontrollable, and not provoked by the environment. Gelastic seizures can number in the hundreds per day, and frequently last for only a few seconds. However, a constant state of seizing, or status gelasticus, has been described.3 Many HH patients present with other seizure types and exhibit presumed secondary epileptogenesis as well. Complex partial seizures are the second most common type. The other seizure types tend to be more responsive to medication than the gelastic seizures.
The second category of presenting symptoms for HH is endocrine disturbance. While precocious puberty is the most common, other endocrinopathies have been seen. Many patients with precocious puberty may be managed on a gonadotropin-releasing–hormone agonist until puberty is appropriate or surgical resection is pursued.
Due to the frequent involvement of the mammillary bodies, patients will often exhibit memory deficits, and may experience declines in school function as they age. This has been considered an indication for treatment as well, as there is potential for improvement subsequently.4 Patients who exhibited the greatest degree of impairment but had the shortest duration of seizures enjoyed the most improvement.
Finally, aggressive behavior and rage attacks are common. Younger patients may require restraints to maintain their safety, while older patients have been institutionalized due to injury to themselves and others. Fortunately, this symptom invariably improves with resection.
14.4 Diagnosis and Neuroimaging
The diagnosis of HH is typically made with magnetic resonance imaging (MRI), as HH have a characteristic appearance on MRI. They are usually hyperintense on T2-weighted and isointense on T1-weighted scans (Fig. 14.1 and Fig. 14.2, Video 14.1). Associated cysts are not uncommon, but there is rarely contrast enhancement. The following are the recommended sequences for optimal diagnosis:
3D T1-weighted MRI, 1-mm isotropic voxels
Sagittal T1-weighted MRI—minimum TE; 3-mm slice, 0.5-mm gap; field of view (FOV) 20 cm
Sagittal T2-weighted MRI (fast spin-echo [FSE])—2-mm slice, no gap; FOV 20 cm
Coronal T2-weighted MRI (FSE)—2-mm slice, no gap; FOV 16 cm
Coronal T1-weighted MRI—3D spoiled gradient echo (SPGR); 2-mm slice; FOV 24 cm—recon for axial
Axial T2 weighted MRI (FSE)—routine brain
The coronal T2-weighted MRI sequence is best for identifying the lesion.
HH have been classified according to the DeLalande classification,5 which is based on location of attachment (Fig. 14.3). Neither functional MRI, diffusion tensor imaging, or PET scan have provided information that has changed diagnosis or management at this time. A correlation between the glial/neuronal fraction has been found with MR spectroscopy. Lesions with a larger glial component tended to be more hyper-intense on T2.6 Although many lesions appear to be attached bilaterally, we frequently find a true attachment only on one side, with the lesion abutting the contralateral side. This detail is not always distinguishable radiographically.
14.5 Treatment
The decision to intervene on a hypothalamic hamartoma is individual, and team-guided. Patients with many gelastic events per day, or in whom the frequency of seizures has progressed, are generally considered for surgery. Similarly, precocious puberty and other endocrine disturbances that are not responsive to medical treatment are also indications for intervention. Finally, there is clear evidence that patients with severe behavioral problems often improve significantly after HH resection. A series of 4 patients treated solely for unmanageable behavior problems (paroxysms of rage, behavior threatening to others) showed dramatic improvement after surgery.7 There are no clear contraindications at this time. As always, the risk of surgical intervention is carefully weighed with the family and care team.
14.5.1 Endoscopic Tumor Resection
With recent improvements in optics, lighting, and resection techniques, small HH lesions or lesions with small attachments are amenable to endoscopic resection. Lesions that are entirely within the third ventricle, or make up the floor, are most amenable to endoscopic resection. If a lesion extends laterally within the suprasellar cistern, it will not be reachable from a single transventricular endoscopic approach. Size remains a significant limitation to neuroendoscopy. We do not recommend attempted resection of lesions over 1.5 cm in size. However, neuroendoscopy can be useful as a second stage approach in resecting large lesions that have been incompletely resected via another approach (Video 14.1 and Video 14.2).
In an endoscopic approach to a hypothalamic hamartoma, the patient is positioned supine with the head in the neutral position. Stereotactic guidance is used to determine the optimal trajectory through the foramen of Monro to the base of the lesion. The ventricle contralateral to the attachment of the lesion is entered using a bur hole and endoscopic sheath. Traversing the foramen of Monro, the lesion is visualized along the contralateral wall (Fig. 14.4). Operating from the ipsilateral side is not recommended due to difficulty achieving the angle necessary to detach the lesion. Initial resection should be aimed at the base of the lesion so as to disconnect it from the hypothalamus (Video 14.1). If this attachment is left for the end of the resection, it can be difficult to achieve a satisfying resection. Hamartomas are favorable because they are hypovascular (Video 14.1 and Video 14.2) and of a consistency that is easily removed with endoscopic pituitary rongeurs. The rongeurs are positioned parallel to the wall of attachment and gently pressed into the lesion while closing. Gentle twisting will then remove the specimen within the rongeur from the surrounding tissue, and the rongeur is then withdrawn. After the specimen is collected, the rongeur is advanced again. The use of two rongeurs in an alternating fashion saves time. Once disconnection has been performed across the base, the lesion is removed, often in one or a few large pieces. The advent of suction and/or cutting devices that fit through an endoscope has improved efficiency, and laser coagulation (thulium) can be used in the place of rongeurs. Similarly, once the gross bulk of the lesion has been removed, an aspiration device or laser can be used to shave the wall if there is suspected residual. External pneumatic, or locking, arms and scope micromanipulators facilitate the tumor resection and reduce the human error inherent with holding a scope for a prolonged period of time. Although this approach should afford a much lower rate of memory loss in theory, the rate of permanent memory loss is ~ 8% in both open and endoscopic series.8
Advantages of the neuroendoscopic approach over the transcranial approach include a faster recovery, shorter hospital stay, and lower surgical complication rate. The main disadvantage is the size restriction. Until endoscopic aspirating devices are more readily available, it is impractical and therefore inadvisable to approach a lesion greater than 1.5 cm. The majority of the resection is performed with micro–pituitary rongeurs, thereby only removing a fraction of a millimeter with each bite (Video 14.1 and Video 14.2). In addition, lesions located more posteriorly in the third ventricle can be more difficult to visualize through the foramen and so place the fornix at greater risk.
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