14.1 Introduction

Hypothalamic hamartoma (HH) is a gray matter lesion that is nonneoplastic and generally occurs within or below the third ventricle. The most common presentations are gelastic seizures and precocious puberty. There has been some correlation between location and presenting symptoms, as lesions within the third ventricle are more likely to cause epilepsy. ¹ Infrequently, lesions are large enough to cause mass effect on adjacent structures or cerebrospinal fluid (CSF) obstruction. The majority of cases are identified in childhood and careful history often reveals that the symptoms have been present since an early age, sometimes since birth. HHs have been classified according to the DeLalande classification, ² which is based on location of attachment (▶Fig. 14.1). Since they are hamartomas, they do not grow disproportionately to 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. ³ The particular types of seizures generated by this tissue are called “gelastic” and are poorly responsive to medical therapy. The morphology and attachment are variable and 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 or attached along the hypothalamic infundibulum. Some lesions have cysts. 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. ⁴ Many HH patients present with other seizure types and exhibit presumed secondary epileptogenesis as well. Complex partial is the most common second type of seizure.

The second category of presenting symptoms for HH is endocrine disturbance. While precocious puberty is the most common, other endocrinopathies have been seen. Diabetes insipidus has been noted before and after surgery, as well as growth hormone deficiency. 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 if they become seizure free. ⁵ 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 also a common presenting symptom. 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 too is very likely to improve with resection.

14.4 Diagnosis and Neuroimaging

The diagnosis of HH is typically made with magnetic resonance imaging (MRI) as HH has a characteristic imaging appearance. They are usually hyperintense on T2 and iso- to hypointense on T1 (▶Fig. 14.2 and ▶Fig. 14.3). Associated cysts are not uncommon, and there is rarely contrast enhancement. The following are the recommended MRI sequences for optimal diagnosis:

1. 
   

   3D T1—1-mm isotropic voxels.

   
   
2. 
   

   Sag T1—min TE; 3 mm slice, 0.5 mm gap; FOV 20 cm.

   
   
3. 
   

   Sag T2 (FSE)—2 mm slice, no gap; FOV 20 cm.

   
   
4. 
   

   Cor T2 (FSE)—2 mm slice, no gap; FOV 16 cm

   
   
5. 
   

   Cor T1—3D SPGR; 2 mm slice; FOV 24 cm, recon for axial.

   
   
6. 
   

   Axial T2 (FSE)—routine brain.

The coronal T2 sequence is best for identifying the lesion.

As mentioned, HH has been classified according to the DeLalande classification, ² which is based on location of attachment. A correlation between the glial/neuronal fraction has been found with MR spectroscopy. Lesions with a larger glial component tended to be more hyperintense 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 on MRI. Unfortunately, standard functional MRI, diffusion tensor imaging, or PET scan have not provided any additional information that has changed diagnosis or management currently. Resting state MRI has more recently been useful in narrowing down the most likely site of attachment and improper signaling. ⁷

14.5 Indications for Intervention

The decision to intervene on a HH is individual, and team guided. Since gelastic epilepsy is poorly responsive to medical therapy, surgical resection is the best option for seizure cessation. However, many HH patients also develop other types of seizures and these other seizure types tend to be more responsive to medication than the gelastic seizures. 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. Many patients with precocious puberty can be managed on Lupron for extended periods of time, although tolerance does occur. Finally, there is emerging evidence that patients with severe behavioral problems may improve significantly after HH resection. A series of four patients treated solely for unmanageable behavior problems (paroxysms of rage, behavior threatening others) showed dramatic improvement after surgery. ⁸ There are no specific contraindications to HH surgery at this time. As always, the risk of surgical intervention is carefully weighed with the family and care team.

There are a number of options for surgical intervention. These include (1) open surgery with craniotomy (interhemispheric or orbitozygomatic), (2) endoscopic resection, (3) stereotactic laser ablation (SLA), and (4) stereotactic radiosurgery. Each has their unique features and indications for use. While stereotactic radiosurgery provides a more minimally invasive treatment option, we have found that efficacy frequently requires 12 to 18 months, even up to 24 months, and some literature encourages waiting up to 3 years. ⁹ As a result, this modality is reserved for patients with milder or less frequent symptoms, or those who are stable with conservative therapy. As with the endoscopic approach, there is a size limitation for radiosurgery. Lesions over 3 cm are not considered suitable for treatment. Lesions that are immediately adjacent to the optic tracts or chiasm are also excluded. As a result, we will focus on open and more minimally invasive surgical techniques.