Hypothalamic Hamartomas: Evolving Understanding and Management

Abstract

Hypothalamic hamartomas (HH) are rare, basilar developmental lesions with widespread comorbidities often associated with refractory epilepsy and encephalopathy. Imaging advances allow for early, even prenatal, detection. Genetic studies suggest mutations in GLI3 and other patterning genes are involved in HH pathogenesis. About 50%-80% of children with HH have severe rage and aggression and a majority of patients exhibit externalizing disorders. Behavioral disruption and intellectual disability may predate epilepsy. Neuropsychological, sleep, and endocrine disorders are typical. The purpose of this article is to provide a summary of the current understanding of HH and to highlight opportunities for future research.

Figure 1. Delalande Classification of Hypothalamic Hamartomas

Type I lesions have horizontal attachment inferior to floor of the third ventricle. Type II lesions have vertical attachment to the wall of third ventricle and are above the floor of the third ventricle. Type III lesions have horizontal and vertical attachments above and below the floor of the third ventricle. Type IV lesions are considered “giant” with volume 8 cm³ or larger (used with permission from Barrow Neurologic Institute, Phoenix, AZ).

Figure 2. MRI Examples of Delalande Classification of Hypothalamic Hamartoma (HH)

All panels show coronal T2-weighted MRI. HH lesion type is designated according to the proposed classification system of Delalande and Fohlen. (A) Type I HH: 2-year-old boy with mild developmental delay but otherwise asymptomatic. Note attachment of the HH lesion entirely below the floor of the third ventricle. (B) Type II HH: 5-year-old boy with a history of gelastic seizures since 12 months of age. Note attachment to the left side of the hypothalamus, entirely above the floor of the third ventricle. (C) Type III HH: 31-year-old woman with refractory epilepsy, including gelastic seizures since infancy. Note attachment of the HH lesion to the right side of the hypothalamus both above and below the floor of the third ventricle. (D) Type IV HH: 3-year-old girl with severe developmental delay, history of precocious puberty, and multiple daily gelastic seizures. Type IV is designated by Delalande and Fohlen as a “giant” HH, but criteria to distinguish between types III and IV were not offered. We (Barrow Neurologic Institute) currently use a volume measurement over 8 cm³ to designate type IV, measuring the maximal length of the lesion in the 3 major axes, then utilizing the formula for determining the volume of an ellipsoid (courtesy of John F. Kerrigan, MD, Barrow Neurologic Institute).