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]

  Two thirds of patients with the latter experience developmental delays, and half also exhibit precocious puberty. [ncbi.nlm.nih.gov]

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

• Accelerated Growth

  The girls sought care at ages 2 years (patient 1) and 4 years (patient 2) due to thelarche and accelerated growth rate. Physical examination revealed the patients were at the Tanner II stage. Hormone testing was performed. [analesdepediatria.org]

• Sneezing

  All older patients reported feelings of embarrassment, and attempts to conceal the seizure (eg. by feigning a sneeze); no feeling of amusement accompanied the laughter. [pediatricneurologybriefs.com]

• 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]

  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. [symptoma.com]

• Focal Neurological Deficit

  No focal neurological deficit was elicited. Computed Tomography scan of brain revealed subependymal tubers in right parietal region [Figure - 1]. [annalsofian.org]

• Frontal Headache

  He also gave history of frontal headache, fatigue, anorexia and irritability since one year. Neurological examination was normal. The bone age was approximately 14 years. [jpgmonline.com]

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.

• 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]

• Abnormal Spikes

  Electroencephalogram recordings suggested abnormal spike and sharp wave discharges localized to left temporal region. Patient was put on carbamazepine, which was build up to 800 mg/day for control of seizures and he responded to treatment. [annalsofian.org]

• Generalized Spike-and-Slow-Waves

  Electroencephalogram showed abnormal generalized spike and slow wave discharges. A neurosurgical opinion was advised which the parents refused and patient was put on carbamazepine. The dose of carbamazepine was gradually built up to 400 mg/day. [annalsofian.org]

• 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]

Consequently, consultation at a referral center that specializes in the treatment of HH is highly recommended. A brief discussion of each of these treatment modalities follows. [rarediseases.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]

The 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 [pediatricneurologybriefs.com]

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]

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

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]

Multiple osteochondromas have a relatively high (1-25%) incidence of malignant transformation. [5] There are many theories regarding the pathophysiology of epiphyseal osteochondromas. [emedicine.medscape.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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