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Hypothalamic Hamartoma

Congenital Hypothalamic Hamartoma Syndrome

Hypothalamic hamartoma is a rare developmental malformation occurring in young children and adults. It neither expands nor metastasizes but instead grows proportionately with the individual's brain. Clinical manifestations include seizures, cognitive impairment, and precocious puberty. The evaluation of endocrinology system along with imaging studies, electroencephalogram and neuropsychiatric tests form the mainstay of diagnosis.


Presentation

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.[ncbi.nlm.nih.gov]
  • Hypothalamic hamartomas (HHs) are benign lesions that are often associated with central precocious puberty and may present with gelastic seizures.[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]
Suicidal Ideation
  • She had a significant psychiatric history including attention deficit hyperactivity disorder, depressed mood, impulsivity, threatening behavior, and suicidal ideation requiring management with dexmethylphenidate, bupropion, and aripiprazole.[ncbi.nlm.nih.gov]
Seizure
  • RESULTS: According to patient history, gelastic seizures had occurred in all patients, in 74% as the initial seizure type at epilepsy onset.[ncbi.nlm.nih.gov]
  • 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]
  • Hypothalamic hamartomas (HH) are typically associated with gelastic seizures but also implicated in the genesis of other seizure types.[ncbi.nlm.nih.gov]
  • Nine patients underwent resective epilepsy surgery for their seizures. Six patients (67%) were seizure-free after surgery. CONCLUSION: In adult patients, gelastic seizures can be seen in patients with focal epilepsy without hypothalamic hamartoma.[ncbi.nlm.nih.gov]
  • […] a reduced frequency of seizures but persistence of some generalized seizures.[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]
Cranial Neuropathy
  • No patient developed post-treatment cranial neuropathy or hypothalamic-pituitary suppression.[ncbi.nlm.nih.gov]

Workup

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]
  • We describe a male infant with Pallister-Hall syndrome who had a large HH presenting with infantile spasms without hypsarrhythmia. [(18)F]fluoro-deoxyglucose positron emission tomography scan performed during the period of epileptic spasms demonstrated[ncbi.nlm.nih.gov]
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]
  • We describe a male infant with Pallister-Hall syndrome who had a large HH presenting with infantile spasms without hypsarrhythmia. [(18)F]fluoro-deoxyglucose positron emission tomography scan performed during the period of epileptic spasms demonstrated[ncbi.nlm.nih.gov]
Neurofibrillary Tangle
  • Herein, we report a case of hypothalamic hamartoma with neurofibrillary tangles.[ncbi.nlm.nih.gov]

Treatment

  • The duration of treatment varied from 2.66 to 8.41 years.[doi.org]
  • No patient developed post-treatment cranial neuropathy or hypothalamic-pituitary suppression.[ncbi.nlm.nih.gov]
  • GnRH analogue treatment was discontinued for 8 months from 9 years and 4 months of age due to his mother's illness. During this period sexual urges were observed. Treatment with daily methylphenidate markedly improved his behavioral problems.[ncbi.nlm.nih.gov]
  • Pretreatment evaluation, patient selection, surgical techniques, complications, and possible selection of treatment are discussed in this chapter.[ncbi.nlm.nih.gov]
  • Successful treatment of hypothalamic hamartoma (HH) can result in the resolution of its sequelae including epilepsy and rage attacks.[ncbi.nlm.nih.gov]

Prognosis

  • 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]
  • Abstract The prognosis for patients with hypothalamic hamartoma has improved dramatically over the last 20 years, for 3 main reasons.[ncbi.nlm.nih.gov]
  • This case illustrates that, despite its immature and proliferative histological appearance, this rare neonatal mass can be regarded as a "differentiating" hypothalamic hamartoma and can have a favorable prognosis.[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]

Etiology

  • More than 50% of boys with CPP have an identifiable etiology. Hypothalamic hamartoma (HH), hydrocephalus, tumors, infections, congenital defects, ischemia, radiation, or injury of the brain are the most common causes of secondary CPP.[ncbi.nlm.nih.gov]
  • 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]
  • In needle biopsy specimens of HH tissue, field potential recordings demonstrated spontaneous epileptiform activities similar to those observed in other etiologically distinct epileptogenic tissues.[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]

Epidemiology

  • […] 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]
Sex distribution
Age distribution

Pathophysiology

  • 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]
  • […] suggesting the possibility that symptoms related to HH are directly associated with the region of anatomic attachment of the HH to the hypothalamus, which determines functional network connections, rather than to differences in HH tissue expression or pathophysiology[ncbi.nlm.nih.gov]
  • Yet the role of the hypothalamic lesion in the pathophysiology of the syndrome remains debatable. In the Strasbourg-Kork series, the best outcomes were obtained when the duration of epilepsy before endoscopic HH surgery did not exceed 10 years.[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]

Prevention

  • 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]

References

Article

  1. Weissenberger AA, Dell ML, Liow K, et al. Aggression and psychiatric comorbidity in children with hypothalamic hamartomas and their unaffected siblings. J Am Acad Child Adolesc Psychiatry. 2001;40:696–703.
  2. Tonn J, Westphal M, Rutka JT. Oncology of CNS Tumors. Springer-Verlag; 2009
  3. Amstutz DR, Coons SW, Kerrigan JF, et al. Hypothalamic hamartomas: Correlation of MR imaging and spectroscopic findings with tumor glial content. AJNR Am J Neuroradiol. 2006;27 (4): 794-8.
  4. Shahar E, Kramer U. MahajnahM, et al. Pediatric-onset gelastic seizures: clinical data and outcome. Pediatr Neurol. 2007;37:29–34.
  5. Engel J, Pedley TA, Aicardi J. Epilepsy: A Comprehensive Textbook. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, c2008; 2007
  6. Valentin A, Lazaro M, Mullatti N, et al. Cingulate epileptogenesis in hypothalamic hamartoma. Epilepsia. 2011;52(5):e35–9.
  7. Arroyo S, Lesser RP, Gordon B, et al. Mirth, laughter and gelastic seizures. Brain. 1993;116(Pt 4):757–8.
  8. Stewart L, Steinbok P, Daaboul J. Role of surgical resection in the treatment of hypothalamic hamartomas causing precocious puberty. Report of six cases. J Neurosurg. 1998;88(2):340–5.
  9. Jung H, Carmel P, Schwartz MS, et al. Some hypothalamic hamartomas contain transforming growth factor alpha, a puberty-inducing growth factor, but not luteinizing hormone-releasing hormone neurons. J Clin Endocrinol Metab. 1999;84:4695–701.
  10. Arita K, Ikawa F, Kurisu K, et al. The relationship between magnetic resonance imaging findings and clinical manifestations of hypothalamic hamartoma. J Neurosurg. 1999;91(2):212–20.
  11. Simon Harvey A, Freeman JL. Epilepsy in Hypothalamic Hamartoma: Clinical and EEG Features. Semin Pediatr Neurol. 2007;14(2):60–4.
  12. Wang B, Ma J. The diagnosis, and management of hypothalamic hamartomas in children.Chinese Neurosurgical Journal. 2016;2:29
  13. Freeman JL, Coleman LT, Wellard RM, et al. MR Imaging and Spectroscopic Study of Epileptogenic Hypothalamic Hamartomas: Analysis of 72 Cases. AJNR Am J Neuroradiol. 2004;25:450–62.

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Last updated: 2019-06-28 10:37