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.

• Precocious Puberty

  Albright AL Lee PA : Neurosurgical treatment of hypothalamic hamartomas causing precocious puberty. J Neurosurg 78 : 77 – 82 1993 Albright AL Lee PA: Neurosurgical treatment of hypothalamic hamartomas causing precocious puberty. [thejns.org]

  To report a rare case of central precocious puberty attributable to hypothalamic hamartoma that was diagnosed in utero. [ncbi.nlm.nih.gov]

  Two thirds of patients with the latter experience developmental delays, and half also exhibit precocious puberty. Conclusions. [doi.org]

• Hypersomnia

  We report a patient with polysomnography findings related to hypersomnia, as a primary presenting symptom, who was shown to have stereotypical gelastic seizures. [ncbi.nlm.nih.gov]

• Poikilothermia

  Residual complications include diabetes insipidus (n   1), poikilothermia (n   1), visual field deficit (n   1), and hemiparesis (n   1). Eight families (80%) reported improved quality of life. [ncbi.nlm.nih.gov]

• Brachydactyly

  These are a group of inherited syndromes that have in common anomalies of the tongue (bifid or lobulated tongue with hamartomas), the face (median cleft lip) and the digits (brachydactyly, polydactyly, clinodactyly and/or syndactyly). [ncbi.nlm.nih.gov]

• Seizure

  Seizure outcome was scored according to Engel's classification. Two patients became free of gelastic and partial complex/generalized seizures seven and nine months after radiosurgery. [ncbi.nlm.nih.gov]

• Cranial Neuropathy

  No patient developed post-treatment cranial neuropathy or hypothalamic-pituitary suppression. [ncbi.nlm.nih.gov]

• Neglect

  The anxious and social features of the aggression suggest that psychiatric interventions, which have been neglected as the emphasis has been on seizure control, are worthwhile in the overall management of this difficult case. [ncbi.nlm.nih.gov]

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.

• Epileptiform Activity

  Ictal fluorodeoxyglucose-positron emission tomography demonstrated a large circumscribed hypermetabolic region within the location of the hypothalamic hamartoma, representing localized intense epileptiform activity. [ncbi.nlm.nih.gov]

  A few children with HH suffering from an epileptic progression usually show lateral focal slowing and epileptiform activity on the interictal EEG [ 44 ]. [cnjournal.biomedcentral.com]

  activity in this pathology, given the deep location of this lesion and the complex connections of the hamartoma. 16 During the early stages of the disease, intercritical EEG findings are usually normal and gelastic seizures show a diffuse depression [elsevier.es]

• Hypsarrhythmia

  These patients may have hypsarrhythmia on initial EEG, and may respond to ACTH treatment with improvement of IS. However, all became refractory with other seizure types, more commonly seen in HH patients. [ncbi.nlm.nih.gov]

• Neurofibrillary Tangle

  Herein, we report a case of hypothalamic hamartoma with neurofibrillary tangles. [ncbi.nlm.nih.gov]

No patient developed post-treatment cranial neuropathy or hypothalamic-pituitary suppression. [ncbi.nlm.nih.gov]

The duration of treatment varied from 2.66 to 8.41 years. [doi.org]

This technique may prove useful for diagnosis, prognosis and treatment planning, as well as to guide transendoscopic therapeutic interventions for HH. [ncbi.nlm.nih.gov]

Categorizing HHs by the degree of hypothalamic involvement has contributed to the accurate prediction of their prognosis and to improved treatment strategies. [jlc.jst.go.jp]

Only 1 patient was not effectively treated ( CONCLUSIONS: Patients with Lennox-Gastaut syndrome symptomatic to hypothalamic hamartomas have better postsurgical outcome due to other etiologies compared with cryptogenic and symptomatic Lennox-Gastaut syndrome [ncbi.nlm.nih.gov]

The etiology of this anomaly and the pathogenesis of its peculiar symptoms remain unclear, but recent electrophysiological, neuroimaging, and clinical studies have yielded important data. [jlc.jst.go.jp]

A genetic etiology has also been suggested. [14] Gelastic Seizure may also be observed in patients without MRI lesions and with normal neurologic status. [annalsofian.org]

[…] preBerger years 174 Chapter 22 History of neuroimaging in the presurgical evaluation 177 Chapter 23 Epilepsy surgery in literature and film 189 Chapter 24 The future of epilepsy surgery 197 Chapter 25 Medical intractability in epilepsy 203 Chapter 26 Epidemiology [books.google.de]

More recent epidemiologic studies have found these associations to be less consistent, with gelastic epilepsy predominant in the majority of patients regardless of morphology. [ipfs.io]

Results Epidemiological and perinatal data ( Table 1 ) Of the 10 patients in our series, 6 were male. Only one patient had a family history of epilepsy. [elsevier.es]

Epidemiology Incidence It is difficult to give an accurate assessment of incidence, as many skin lesions are simply ignored as 'birthmarks' and many internal lesions are incidental findings. [patient.info]

First, because of improved understanding of the anatomy and pathophysiology of these varied lesions.Second, due to advances in brain imaging and refinements in microsurgery, including the anterior transcallosal interforniceal approach, endoscopic, and [ncbi.nlm.nih.gov]

This review of hypothalamic hamartomas presents current classifications, pathophysiologies, and treatment modalities. [jlc.jst.go.jp]

By the nature and pathophysiology of HHs the complete disconnection from the surrounding structure and tracts which spread out its epileptogenic discharge to frontotemporal region will be enough to achieve the appropriate control of accompanying problems [wjgnet.com]

The accumulation of knowledge regarding the pathogenesis of symptoms and the development of safe, effective treatment modalities may lead to earlier intervention in young HH patients and prevent the decline in their cognitive abilities and quality of [jlc.jst.go.jp]

[…] prognosis is usually poor, the GS evolving into symptomatic generalized epilepsy and leading to cognitive deterioration, but early recognition and surgical ablation of the hamartoma may occasionally result in control of drug refractory seizures and prevention [pediatricneurologybriefs.com]

Generally, AEDs (Antiepileptic drugs) are ineffective for GSs associated with HH and rarely prevent cognitive and behavioral deterioration. [spandidos-publications.com]

Approximately 25% of optic nerve gliomas do not enhance, so a lack of enhancement should not prevent you from making the diagnosis. This is another example of a right-sided optic nerve glioma with enhancement after gadolinium. [radiologyassistant.nl]

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