Child's Nervous System

, Volume 22, Issue 8, pp 867–873 | Cite as

Hypothalamic hamartomas—clinical, neuropathological and surgical aspects

  • Wirginia MaixnerEmail author
Special Annual Issue



Hypothalamic hamartomas are rare congenital lesions of the tuber cinereum presenting with the classic triad of gelastic epilepsy, central precocious puberty and developmental delay. The clinical course in the majority is one of progression, commencing with gelastic seizures in infancy, deteriorating into more complex seizure disorders and resulting in a catastrophic epilepsy associated with a concomitant cognitive and behavioural decline.


Electrophysiological, radiological and pathophysiological studies have confirmed the intrinsic epileptogenicity of the hypothalamic hamartoma. Secondary generalised epilepsy seen in this condition is theorised to be through propagation via the mamillothalamic pathways with attachment to the mamillary bodies identified on MRI. Indications as to timing for surgery remain ill-defined although there is a theoretical argument to intervene before the development of secondary generalised epilepsy.

Surgical approach

Currently, the most effective surgical route appears to be the transcallosal anterior interforniceal approach although newer approaches of endoscopic disconnection and radiosurgery are being assessed.


Hypothalamic Hamartoma Epilepsy surgery Gelastic seizures 


  1. 1.
    Andermann F, Arzimanoglou A, Berkovic SF (2003) Hypothalamic hamartoma and epilepsy: the pathway of discovery. Epileptic Disord 5:173–175PubMedGoogle Scholar
  2. 2.
    Arita K, Ikawa F, Kurisu K, Sumida M, Harada K, Uozumi T, Monden S, Yoshida J, Nishi Y (1999) The relationship between magnetic resonance imaging findings and clinical manifestations of hypothalamic hamartoma. J Neurosurg 91:212–220PubMedCrossRefGoogle Scholar
  3. 3.
    Arroyo S, Lesser RP, Gordon B, Uematsu S, Hart J, Schwerdt P, Andreasson K, Fisher RS (1993) Mirth, laughter and gelastic seizures. Brain 116(Pt 4):757–780PubMedCrossRefGoogle Scholar
  4. 4.
    Arzimanoglou AA, Hirsch E, Aicardi J (2003) Hypothalamic hamartoma and epilepsy in children: illustrative cases of possible evolutions. Epileptic Disord 5:187–199PubMedGoogle Scholar
  5. 5.
    Berkovic SF, Andermann F, Melanson D, Ethier RE, Feindel W, Gloor P (1988) Hypothalamic hamartomas and ictal laughter: evolution of a characteristic epileptic syndrome and diagnostic value of magnetic resonance imaging. Ann Neurol 23:429–439PubMedCrossRefGoogle Scholar
  6. 6.
    Berkovic SF, Kuzniecky RI, Andermann F (1997) Human epileptogenesis and hypothalamic hamartomas: new lessons from an experiment of nature. Epilepsia 38:1–3PubMedCrossRefGoogle Scholar
  7. 7.
    Boudreau EA, Liow K, Frattali CM, Wiggs E, Turner JT, Feuillan P, Sato S, Patsalides A, Patronas N, Biesecker LG, Theodore WH (2005) Hypothalamic hamartomas and seizures: distinct natural history of isolated and Pallister-Hall syndrome cases. Epilepsia 46:42–47PubMedCrossRefGoogle Scholar
  8. 8.
    Cascino GD, Andermann F, Berkovic SF, Kuzniecky RI, Sharbrough FW, Keene DL, Bladin PF, Kelly PJ, Olivier A, Feindel W (1993) Gelastic seizures and hypothalamic hamartomas: evaluation of patients undergoing chronic intracranial EEG monitoring and outcome of surgical treatment. Neurology 43:747–750PubMedGoogle Scholar
  9. 9.
    Choi JU, Yang KH, Kim TG, Chang JH, Chang JW, Lee BI, Kim DS (2004) Endoscopic disconnection for hypothalamic hamartoma with intractable seizure. Report of four cases. J Neurosurg 100:506–511PubMedGoogle Scholar
  10. 10.
    Coulter D (1997) Thalamocortical anatomy and physiology. In: Engel J, Pedley T (eds) Epilepsy: a comprehensive textbook. Lippincott-Raven, Philadelphia, pp 341–351Google Scholar
  11. 11.
    Delalande O, Fohlen M (2003) Disconnecting surgical treatment of hypothalamic hamartoma in children and adults with refractory epilepsy and proposal of a new classification. Neurol Med Chir (Tokyo) 43:61–68CrossRefGoogle Scholar
  12. 12.
    DiFazio MP, Davis RG (2000) Utility of early single photon emission computed tomography (SPECT) in neonatal gelastic epilepsy associated with hypothalamic hamartoma. J Child Neurol 15:414–417PubMedCrossRefGoogle Scholar
  13. 13.
    Fohlen M, Lellouch A, Delalande O (2003) Hypothalamic hamartoma with refractory epilepsy: surgical procedures and results in 18 patients. Epileptic Disord 5:267–273PubMedGoogle Scholar
  14. 14.
    Frattali CM, Liow K, Craig GH, Korenman LM, Makhlouf F, Sato S, Biesecker LG, Theodore WH (2001) Cognitive deficits in children with gelastic seizures and hypothalamic hamartoma. Neurology 57:43–46PubMedGoogle Scholar
  15. 15.
    Freeman JL, Harvey AS, Rosenfeld JV, Wrennall JA, Bailey CA, Berkovic SF (2003) Generalized epilepsy in hypothalamic hamartoma: evolution and postoperative resolution. Neurology 60:762–767PubMedGoogle Scholar
  16. 16.
    Freeman JL, Coleman LT, Wellard RM, Kean MJ, Rosenfeld JV, Jackson GD, Berkovic SF, Harvey AS (2004) MR imaging and spectroscopic study of epileptogenic hypothalamic hamartomas: analysis of 72 cases. AJNR Am J Neuroradiol 25:450–462PubMedGoogle Scholar
  17. 17.
    Harvey AS, Freeman JL, Berkovic SF, Rosenfeld JV (2003) Transcallosal resection of hypothalamic hamartomas in patients with intractable epilepsy. Epileptic Disord 5:257–265PubMedGoogle Scholar
  18. 18.
    Iannetti P, Chessa L, Raucci U, Basile LA, Fantozzi LM, Bozzao L (1992) Gelastic epilepsy. A clinical contribution. Clin Pediatr (Phila) 31:467–470CrossRefGoogle Scholar
  19. 19.
    Kahane P, Munari C, Minotti L (1997) The role of the hypothalamic hamartoma in the genesis of gelastic and dacrystic seizures. In: Tuxhorn I, Hothausen H, Boenigk K (eds) Paediatric epilepsy syndromes and their surgical treatment. John Libbey, London, pp 447–461Google Scholar
  20. 20.
    Kerrigan JF, Ng YT, Chung S, Rekate HL (2005) The hypothalamic hamartoma: a model of subcortical epileptogenesis and encephalopathy. Semin Pediatr Neurol 12:119–131PubMedCrossRefGoogle Scholar
  21. 21.
    Kuzniecky R, Guthrie B, Mountz J, Bebin M, Faught E, Gilliam F, Liu HG (1997) Intrinsic epileptogenesis of hypothalamic hamartomas in gelastic epilepsy. Ann Neurol 42:60–67PubMedCrossRefGoogle Scholar
  22. 22.
    Leal AJ, Moreira A, Robalo C, Ribeiro C (2003) Different electroclinical manifestations of the epilepsy associated with hamartomas connecting to the middle or posterior hypothalamus. Epilepsia 44:1191–1195PubMedCrossRefGoogle Scholar
  23. 23.
    Machado HR, Hoffman HJ, Hwang PA (1991) Gelastic seizures treated by resection of a hypothalamic hamartoma. Childs Nerv Syst 7:462–465PubMedCrossRefGoogle Scholar
  24. 24.
    Morrell F (1989) Varieties of human secondary epileptogenesis. J Clin Neurophysiol 6:227–275PubMedCrossRefGoogle Scholar
  25. 25.
    Mullatti N (2003) Hypothalamic hamartoma in adults. Epileptic Disord 5:201–204PubMedGoogle Scholar
  26. 26.
    Mullatti N, Selway R, Nashef L, Elwes R, Honavar M, Chandler C, Morris R, Jarosz J, Buchanan C, Polkey C (2003) The clinical spectrum of epilepsy in children and adults with hypothalamic hamartoma. Epilepsia 44:1310–1319PubMedCrossRefGoogle Scholar
  27. 27.
    Munari C, Kahane P, Francione S, Hoffmann D, Tassi L, Cusmai R, Vigevano F, Pasquier B, Betti OO (1995) Role of the hypothalamic hamartoma in the genesis of gelastic fits (a video-stereo-EEG study). Electroencephalogr Clin Neurophysiol 95:154–160PubMedCrossRefGoogle Scholar
  28. 28.
    Murphy JV, Wheless JW, Schmoll CM (2000) Left vagal nerve stimulation in six patients with hypothalamic hamartomas. Pediatr Neurol 23:167–168PubMedCrossRefGoogle Scholar
  29. 29.
    Ng YT, Kerrigan JF, Prenger EC, White WL, Rekate HL (2005) Successful resection of a hypothalamic hamartoma and a Rathke cleft cyst. Case report. J Neurosurg 102:78–80PubMedGoogle Scholar
  30. 30.
    Nishio S, Morioka T, Fukui M, Goto Y (1994) Surgical treatment of intractable seizures due to hypothalamic hamartoma. Epilepsia 35:514–519PubMedCrossRefGoogle Scholar
  31. 31.
    Northfield DW, Russell DS (1967) Pubertas praecox due to hypothalamic hamartoma: report of two cases surviving surgical removal of the tumour. J Neurol Neurosurg Psychiatry 30:166–173PubMedCrossRefGoogle Scholar
  32. 32.
    Paillas J, Roger J, Toga M (1969) Hamartoma of the hypothalamus. Clinical, radiological and histological study. Results of excision. Rev Neurol 120:177–194PubMedGoogle Scholar
  33. 33.
    Palmini A, Chandler C, Andermann F, Costa Da Costa J, Paglioli-Neto E, Polkey C, Rosenblatt B, Montes J, Martinez JV, Farmer JP, Sinclair B, Aronyk K, Paglioli E, Coutinho L, Raupp S, Portuguez M (2002) Resection of the lesion in patients with hypothalamic hamartomas and catastrophic epilepsy. Neurology 58:1338–1347PubMedGoogle Scholar
  34. 34.
    Palmini A, Paglioli-Neto E, Montes J, Farmer JP (2003) The treatment of patients with hypothalamic hamartomas, epilepsy and behavioural abnormalities: facts and hypotheses. Epileptic Disord 5:249–255PubMedGoogle Scholar
  35. 35.
    Palmini A, Van Paesschen W, Dupont P, Van Laere K, Van Driel G (2005) Status gelasticus after temporal lobectomy: ictal FDG–PET findings and the question of dual pathology involving hypothalamic hamartomas. Epilepsia 46:1313–1316PubMedCrossRefGoogle Scholar
  36. 36.
    Polkey CE (2003) Resective surgery for hypothalamic hamartoma. Epileptic Disord 5:281–286PubMedGoogle Scholar
  37. 37.
    Sato M, Ushio Y, Arita N, Mogami H (1985) Hypothalamic hamartoma: report of two cases. Neurosurgery 16:198–206PubMedCrossRefGoogle Scholar
  38. 38.
    Striano S, Meo R, Bilo L, Cirillo S, Nocerino C, Ruosi P, Striano P, Estraneo A (1999) Gelastic epilepsy: symptomatic and cryptogenic cases. Epilepsia 40:294–302PubMedCrossRefGoogle Scholar
  39. 39.
    Tassinari C, Riguzzi P, Rizzi R (1997) Gelastic seizures. In: Tuxhorn I, Holthausen H, Boenigk K (eds) Paediatric epilepsy syndromes and their surgical management. John Libbey, London, pp 429–446Google Scholar
  40. 40.
    Weissenberger AA, Dell ML, Liow K, Theodore W, Frattali CM, Hernandez D, Zametkin AJ (2001) Aggression and psychiatric comorbidity in children with hypothalamic hamartomas and their unaffected siblings. J Am Acad Child Adolesc Psychiatry 40:696–703PubMedCrossRefGoogle Scholar
  41. 41.
    Wu J, Xu L, Kim do Y, Rho JM, St John PA, Lue LF, Coons S, Ellsworth K, Nowak L, Johnson E, Rekate H, Kerrigan JF (2005) Electrophysiological properties of human hypothalamic hamartomas. Ann Neurol 58:371–382PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Department of Neurosurgery, Children’s Neuroscience CentreRoyal Children’s HospitalVictoriaAustralia

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