Hypothalamic Hamartoma

Hypothalamic hamartoma (HH), or tuber cinereum hamartoma is a congenital malformation with an incidence of 1-2 per 100,000 [1]. This tumor-like lesion is situated in the tuber cinereum of the hypothalamus in the region of the optic chiasma and mammillary bodies. Usually, HH is observed as an isolated lesion, although cases in association with Pallister-Hall syndrome have also been reported [2].

The clinical presentation of HH is variable but is associated with gelastic seizures, visual dysfunction, early onset puberty and neuropsychiatric impairment [3]. The onset of symptoms is as early as the 2nd or 3rd year of life and progresses over the years.

Gelastic seizures occur in neonates and children, last for 2 to 30 seconds and are characterized by uncontrollable laughter with recurrent seizures without loss of consciousness. The prevalence of these seizures is 1 in 200,000 [4]. Rarely, status gelasticus can also occur [5]. Subsequently, the patients may develop other types of seizures like myoclonic, tonic or generalized [6]. Cognitive and neuropsychiatric symptoms are seen only in cases of HH with epilepsy [7] [8]. These include delayed development, cognitive dysfunction, and rage.

Early onset puberty is a typical clinical feature of large, pedunculated HH [9] [10] and can be observed even in children under the age of 3 years. It is seen in 40% of HH patients with seizures.

The workup in HH depends on neuroimaging with magnetic resonance imaging (MRI) being the gold standard for confirming or excluding the diagnosis. However, it is difficult to perform due to interference with motion artifacts and also because it could be normal in some of the patients. Computed tomograms are associated with radiation exposure (especially important in small children) and are also unable to detect small HH.

History and physical examination, especially by an endocrinologist are essential in children with early onset puberty. Laboratory tests for reproductive hormone levels along with levels of adrenal, growth hormone and thyroid hormone are indicated in these children.

An electroencephalogram (EEG) is performed in all HH patients with seizures. It may be normal in very young children with gelastic seizures but is usually abnormal in older HH patients who develop other types of seizures. A lateral slowing and epileptiform features in interictal EEG can be observed in progressive epilepsy [11] followed by seizure specific features like bilateral synchronous or generalized activity when other types of epilepsy develop [12].

Findings of HH on MRI are non-enhancing lesions with 93% being hyperintense on T2 and 74% being hypointense on T1 weighted images [13]. Morphologically, HH can be classified as sessile, broad-based or pedunculated [2] [3]. Sessile HH is connected to the mammillary bodies, causing their distortion and displacement, if large [2] Pedunculated HH extend into the suprasellar space and are attached to the tuber cinereum.

Neuropsychological tests help to evaluate the memory, language skills and ability of the patients to solve problems as HH patients with epilepsy often suffer from progressive developmental and cognitive deficits. The tests also are useful to plan treatment and record improvement (after therapy and surgery) or deterioration over time.

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