Seminars in Pediatric Neurology
Volume 12, Issue 2 , Pages 119-131 , June 2005

The Hypothalamic Hamartoma: A Model of Subcortical Epileptogenesis and Encephalopathy

  • John F. Kerrigan, MD

      Affiliations

    • Division of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ.
    • Children’s Health Center, St. Joseph’s Hospital and Medical Center, Phoenix, AZ.
    • Corresponding Author InformationAddress reprint requests to John F. Kerrigan, MD, Division of Pediatric Neurology, Barrow Neurological Institute, 500 West Thomas Road, S-930, Phoenix, AZ 85013.
  • ,
  • Yu-tze Ng, MD

      Affiliations

    • Division of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ.
    • Children’s Health Center, St. Joseph’s Hospital and Medical Center, Phoenix, AZ.
  • ,
  • Steven Chung, MD

      Affiliations

    • Division of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ.
  • ,
  • Harold L. Rekate, MD

      Affiliations

    • Division of Neurosurgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ.

References 

  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. Trousseau A . De l’epilepsie . In:  Peter MM editors. Clinique Medicale de l’Hotel-Dieu de Paris . Paris: Librarie J. B. Bailliere; 1877;
  3. Dott NM . Surgical aspects of the hypothalamus . In:  Le Gros Clark WE ,  Beattie J ,  Riddoch G , et al. editor. The Hypothalamus (Morphological, Functional, Clinical and Surgical aspects) . Edinburgh: Oliver and Boyd; 1938;p. 131–185
  4. Martin JP . Fits of laughter (sham mirth) in organic cerebral disease . Brain . 1950;73:453–464
  5. Daly DD , Mulder DW . Gelastic epilepsy . Neurology . 1957;7:189–192
  6. List CF , Dowman CE , Bagchi BK , et al.   Posterior hypothalamic hamartomas and gangliogliomas causing precocious puberty . Neurology . 1958;8:164–174
  7. Berkovic SF , Andermann F , Melanson D , et al.   Hypothalamic hamartomas and ictal laughter (evolution of a characteristic epileptic syndrome and diagnostic value of magnetic resonance imaging) . Ann Neurol . 1988;23:429–439
  8. Nguyen D , Singh S , Zaatreh M , et al.   Hypothalamic hamartomas (seven cases and review of the literature) . Epilepsy Behav . 2003;4:246–258
  9. 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;25:450–462
  10. Boyko OB , Curnes JT , Oakes WJ , et al.   Hamartomas of the tuber cinereum (CT, MR, and pathologic findings) . AJNR Am J Neuroradiol . 1991;12:309–314
  11. Valdueza JM , Cristante L , Dammann O , et al.   Hypothalamic hamartomas (with special reference to gelastic epilepsy and surgery) . Neurosurgery . 1994;34:949–958
  12. Arita K , Ikawa F , Kurisu K , et al.   The relationship between magnetic resonance imaging findings and clinical manifestations of hypothalamic hamartoma . J Neurosurg . 1999;91:212–220
  13. Debeneix C , Bourgeois M , Trivin C , et al.   Hypothalamic hamartoma (comparison of clinical presentation and magnetic resonance images) . Horm Res . 2001;56:12–18
  14. Jung H , Probst EN , Hauffa BP , et al.   Association of morphological characteristics with precocious puberty and/or gelastic seizures in hypothalamic hamartoma . J Clin Endocrinol Metab . 2003;88:4590–4595
  15. Arzimanoglou AA , Hirsch E , Aicardi J . Hypothalamic hamartoma and epilepsy in children (illustrative cases of possible evolutions) . Epileptic Disord . 2003;5:187–199
  16. Harvey AS , Freeman JL , Berkovic SF , et al.   Transcallosal resection of hypothalamic hamartomas in patients with intractable epilepsy . Epileptic Disord . 2003;5:257–265
  17. Sturm JW , Andermann F , Berkovic SF . Pressure to laugh (an unusual epileptic syndrome associated with small hypothalamic hamartomas) . Neurology . 2000;54:971–973
  18. Iannetti P , Chessa L , Raucci U , et al.   Gelastic epilepsy (a clinical contribution) . Clin Pediatr . 1992;31:467–470
  19. Arroyo S , Lesser RP , Gordon B , et al.   Mirth, laughter and gelastic seizures . Brain . 1993;116:757–780
  20. Tassinari CA , Riguzzi P , Rizzi R , et al.   Gelastic seizures . In:  Tuxhorn I ,  Holthausen H ,  Boenigk K editor. Paediatric Epilepsy Syndromes and Their Surgical Treatment . London: John Libbey; 1977;p. 429–446
  21. Mullati N , Selway R , Nashef L , et al.   The clinical spectrum of epilepsy in children and adults with hypothalamic hamartoma . Epilepsia . 2003;44:1310–1319
  22. Frattali CM , Liow K , Craig GH , et al.   Cognitive deficits in children with gelastic seizures and hypothalamic hamartoma . Neurology . 2001;57:43–46
  23. Leal AJR , Moreira A , Robalo C , et al.   Different electroclinical manifestations of the epilepsy associated with hamartomas connecting to the middle or posterior hypothalamus . Epilepsia . 2003;44:1191–1195
  24. Berkovic SF , Arzimanoglou A , Kuzniecky R , et al.   Hypothalamic hamartoma and seizures (a treatable epileptic encephalopathy) . Epilepsia . 2003;44:969–973
  25. Freeman JL , Harvey AS , Rosenfeld JV , et al.   Generalized epilepsy in hypothalamic hamartoma (evolution and postoperative resolution) . Neurology . 2003;60:762–767
  26. Machado HR , Hoffman HJ , Hwang PA . Gelastic seizures treated by resection of a hypothalamic hamartoma . Childs Nerv Syst . 1991;7:462–465
  27. Berkovic SF , Kuzniecky RI , Andermann F . Human epileptogenesis and hypothalamic hamartomas (new lessons from an experiment of nature) . Epilepsia . 1997;38:1–3
  28. Deonna T , Ziegler AL . Hypothalamic hamartoma, precocious puberty and gelastic seizures (a special model of “epileptic” developmental disorder) . Epileptic Disord . 2000;2:33–37
  29. Savard G , Bhanji NH , Dubeau F , et al.   Psychiatric aspects of patients with hypothalamic hamartoma and epilepsy . Epileptic Disord . 2003;5:229–234
  30. Palmini A , Chandler C , Andermann F , et al.   Resection of the lesion in patients with hypothalamic hamartoma and catastrophic epilepsy . Neurology . 2002;58:1338–1347
  31. Andermann F , Arzimanoglou A , Berkovic SF . Hypothalamic hamartoma and epilepsy (the pathway of discovery) . Epileptic Disord . 2003;5:173–175
  32. Palmini A , Paglioli-Neto E , Montes J , et al.   The treatment of patients with hypothalamic hamartomas, epilepsy and behavioural abnormalities (facts and hypotheses) . Epileptic Disord . 2003;5:249–255
  33. Hall JG , Pallister PD , Clarren SK , et al.   Congenital hypothalamic hamartoblastoma, hypopituitarism, imperforate anus and postaxial polydactyly—a new syndrome? Part I: clinical, causal, and pathogenetic considerations . Am J Med Genet . 1980;7:47–74
  34. Kang S , Allen J , Graham JM , et al.   Linkage mapping and phenotypic analysis of autosomal dominant Pallister-Hall syndrome . J Med Genet . 1997;34:441–446
  35. Kang S , Graham JM , Olney AH , et al.   Gli3 frameshift mutations cause autosomal dominant Pallister-Hall syndrome . Nat Genet . 1997;15:266–268
  36. Freeman JL, Wallace RH, Izzillo PA, et al: Hypothalamic hamartoma due to a somatic mutation in transcription factor gene Gli3. Epilepsia 44:68–69 (suppl 9)
  37. Cascino GD , Andermann F , Berkovic SF , et al.   Gelastic seizures and hypothalamic hamartomas (evaluation of patients undergoing chronic intracranial EEG monitoring and outcome of surgical treatment) . Neurology . 1993;43:747–750
  38. Munari C , Kahane P , Francione S , et al.   Role of the hypothalamic hamartoma in the genesis of gelastic fits (a video-stereo-EEG study) . Electroencephalogr Clin Neurophysiol . 1995;95:154–160
  39. Kuzniecky R , Guthrie B , Mountz J , et al.   Intrinsic epileptogenesis of hypothalamic hamartomas in gelastic epilepsy . Ann Neurol . 1997;42:60–67
  40. Tasch E , Cendes F , Li LM , et al.   Hypothalamic hamartomas and gelastic epilepsy (a spectroscopic study) . Neurology . 1998;51:1046–1050
  41. Fukuda M , Kaeyama S , Wachi M , et al.   Stereotaxy for hypothalamic hamartoma with intractable gelastic seizures. Technical case report . Neurosurgery . 1999;44:1347–1350
  42. Kahane P , Ryvlin P , Hoffmann D , et al.   From hypothalamic hamartoma to cortex (what can be learnt (sic) from depth recordings and stimulation) . Epileptic Disord . 2003;5:205–217
  43. Leal AJ , Passao V , Calado E , et al.   Interictal spike EEG source analysis in hypothalamic hamartoma epilepsy . Clin Neurophysiol . 2002;113:1961–1969
  44. Arroyo S , Santamaria J , Sanmarti F , et al.   Ictal laughter associated with paroxysmal hypothalamopituitary dysfunction . Epilepsia . 1997;38:114–117
  45. Norden AD , Blumenfeld H . The role of subcortical structures in human epilepsy . Epilepsy Behavior . 2002;3:219–231
  46. Tuxhorn I , Holthausen H , Boenigk H . Paediatric Epilepsy Syndromes and Their Surgical Treatment . London: John Libbey; 1997;
  47. Cibula JE , Gilmore RL . Secondary epileptogenesis in humans . J Clin Neurophysiol . 1997;14:111–127
  48. Wilder BJ . The mirror focus and secondary epileptogenesis . Int Rev Neurobiol . 2001;45:435–446
  49. Dudek FE , Spitz M . Hypothetical mechanisms for the cellular and neurophysiologic basis of secondary epileptogenesis (proposed role of synaptic reorganization) . J Clin Neurophysiol . 1997;14:90–101
  50. Papez JW . Visceral brain, its component parts and their connections . J Nerv Ment Dis . 1958;126:40–56
  51. Mirski MA , Rossell LA , Terry JB , et al.   Anticonvulsant effect of anterior thalamic high frequency electrical stimulation in the rat . Epilepsy Res . 1997;28:89–100
  52. Mirski MA , Fisher RS . Electrical stimulation of the mamillary nuclei increases seizure threshold to pentylenetetrazol in rats . Epilepsia . 1994;35:1309–1316
  53. Mirski MA , McKeon AC , Ferrendelli JA . Anterior thalamus and substantia nigra (two distinct structures mediating experimental generalized seizures) . Brain Res . 1986;397:377–380
  54. Hodaie M , Wennberg RA , Dostrovsky JO , et al.   Chronic anterior thalamus stimulation for intractable epilepsy . Epilepsia . 2002;43:603–608
  55. Kerrigan JF , Litt B , Fisher RS , et al.   Electrical stimulation of the anterior nucleus of the thalamus for the treatment of intractable epilepsy . Epilepsia . 2004;45:346–354
  56. Nolte J . The Human Brain (An Introduction to Its Functional Anatomy) . (ed 4). St. Louis, MO: Mosby; 1999;
  57. Saper CB . Hypothalamus . In:  Paxinos G editors. The Human Nervous System . San Diego, CA: Academic Press; 1990;p. 389–413
  58. Kahane P , Tassi L , Hoffmann D , et al.   Crises dacrystiques et hamartome hypothalamique. A propos d’une observation video-stereo-EEG . Epilepsies . 1994;6:259–279
  59. Sisodiya SM , Free SL , Stevens JM , et al.   Widespread cerebral structural changes in two patients with gelastic seizures and hypothalamic hamartomata . Epilepsia . 1997;38:1008–1010
  60. Morrell F . Secondary epileptogenesis in man . Arch Neurol . 1985;42:318–335
  61. Rosenfeld JV , Harvey AS , Wrennall J , et al.   Transcallosal resection of hypothalamic hamartomas, with control of seizures, in children with gelastic epilepsy . Neurosurgery . 2001;48:108–118
  62. Fohlen M , Lellouch A , Delalande O . Hypothalamic hamartoma with refractory epilepsy (surgical procedures and results in 18 patients) . Epileptic Disord . 2003;5:267–273
  63. Regis J , Bartolomei F , de Toffol B , et al.   Gamma knife surgery for epilepsy related to hypothalamic hamartomas . Neurosurgery . 2000;47:1343–1352
  64. Kuzniecky RI , Guthrie BL . Stereotactic surgical approach to hypothalamic hamartomas . Epileptic Disord . 2003;5:275–280
  65. Murphy JV , Wheless JW , Schmoll CM . Left vagal nerve stimulation in six patients with hypothalamic hamartomas . Pediatr Neurol . 2000;23:167–168
  66. Kammer KS , Perlman K , Humphreys RP , et al.   Clinical and surgical aspects of hypothalamic hamartoma associated with precocious puberty in a 15-month-old boy . Childs Brain . 1980;7:150–157
  67. Price RA , Lee PA , Albright AL , et al.   Treatment of sexual precocity by removal of a luteinizing hormone releasing hormone secreting hamartoma . JAMA . 1984;251:2247–2249
  68. Mahachoklertwattana P , Kaplan SL , Grumbach MM . The luteinizing hormone-releasing hormone-secreting hypothalamic hamartoma is a congenital malformation (natural history) . J Clin Endocrinol Metab . 1993;77:118–124
  69. Breningstall GN . Gelastic seizures, precocious puberty, and hypothalamic hamartoma . Neurology . 1985;35:1180–1183
  70. Breningstall GN . Gelastic seizures, precocious puberty, and hypothalamic hamartoma . Reply to letter Neurology . 1986;36:444
  71. Northfield DW , Russell DS . Pubertas praecox due to hypothalamic hamartoma (report of two cases surviving surgical removal of the tumour) . J Neurol Neurosurg Psychiatry . 1967;30:166–173
  72. Takeuchi J , Handa H , Miki Y , et al.   Precocious puberty due to a hypothalamic hamartoma . Surg Neurol . 1979;11:456–460
  73. Sato M , Ushio Y , Arita N , et al.   Hypothalamic hamartoma (report of two cases) . Neurosurgery . 1985;16:198–206
  74. Nishio S , Morioko T , Fukui M , et al.   Surgical treatment of intractable seizures due to hypothalamic hamartoma . Epilepsia . 1994;35:514–519
  75. Ponsot G , Diebler C , Plouin P , et al.   Hamartomes hypothalamiques et crises de rire. A propos de 7 observations . Arch Fr Pediatr . 1983;40:757–761
  76. Delalande O , Fohlen M . Disconnecting surgical treatment of hypothalamic hamartoma in children and adults with refractory epilepsy and proposal of a new classification . Neurol Med Chir (Tokyo) . 2003;43:61–68
  77. Polkey CE . Resective surgery for hypothalamic hamartoma . Epileptic Disord . 2003;5:281–286
  78. Rosenfeld JV , Freeman JL , Harvey AS . Operative technique (the anterior transcallosal transeptal interforniceal approach to the third ventricle and resection of hypothalamic hamartomas) . J Clin Neurosci . 2004;11:738–744
  79. Feiz-Erfan I, Horn EM, Rekate HL, et al: Surgical strategies to approach hypothalamic hamartomas causing gelastic seizures in the pediatric population: transventricular versus skull base approaches. J Neurosurg (Pediatrics) (in press)
  80. Nishio S , Fujiwara S , Aiko Y , et al.   Hypothalamic hamartoma. Report of two cases . J Neurosurg . 1989;70:640–645
  81. Polkey CE , Chandler C , Doshi P , et al.   Resection of hypothalamic hamartoma for intractable epilepsy . Epilepsia . 1997;38:77; (abstr)
  82. Watanabe T , Enomoto T , Uemura K , et al.   [Gelastic seizures treated by partial resection of a hypothalamic hamartoma] . No Shinkei Geka . 1998;26:923–928
  83. Mottolese C , Stan H , Bret P , et al.   Hypothalamic hamartoma (the role of surgery in a series of eight patients) . Childs Nerv Syst . 2001;17:229–236
  84. Likavec AM , Dickerman RD , Heiss JD , et al.   Retrospective analysis of surgical treatment outcomes for gelastic seizures (a review of the literature) . Seizure . 2000;9:204–207
  85. Freeman JL , Zacharin M , Rosenfeld JV , et al.   The endocrinology of hypothalamic hamartoma surgery for intractable epilepsy . Epileptic Disord . 2003;5:239–247
  86. Ng Y-t , Kerrigan JF , Prenger EC , et al.   Successful resection of a hypothalamic hamartoma and a Rathke cleft cyst . J Neurosurg (Pediatrics) . 2005;102:78–80
  87. Akai T , Okamoto K , Iizuka H , et al.   Treatments of hamartoma with neuroendoscopic surgery and stereotactic radiosurgery (a case report) . Minim Invasive Neurosurg . 2002;45:235–239
  88. Ng YT , Chung SS , Kerrigan JF , et al.   Endoscopic resection of hypothalamic hamartoma . Ann Neurol . 2004;56(suppl 8):S117; abstr
  89. Arita K , Kurisu K , Iida K , et al.   Subsidence of seizure induced by stereotactic radiation in a patient with hypothalamic hamartoma. Case report . J Neurosurg . 1998;89:645–648
  90. Unger F , Schrottner O , Haselberger K , et al.   Gamma knife radiosurgery for hypothalamic hamartomas in patients with medically intractable epilepsy and precocious puberty. Report of two cases . J Neurosurg . 2000;92:726–731
  91. Dunoyer C , Ragheb J , Resnick T , et al.   The use of radiosurgery to treat intractable childhood partial epilepsy . Epilepsia . 2002;43:292–300
  92. Parrent AG . Stereotactic radiofrequency ablation for the treatment of gelastic seizures associated with hypothalamic hamartoma. Case report . J Neurosurg . 1999;91:881–884
  93. Fujimoto Y , Kato A , Saitoh Y , et al.   Stereotactic radiofrequency ablation for sessile hypothalamic hamartoma with an image fusion technique . Acta Neurochir (Wien) . 2003;145:697–701
  94. Schulze-Bonhage A , Homberg V , Trippel M , et al.   Interstitial radiosurgery in the treatment of gelastic epilepsy due to hypothalamic hamartomas . Neurology . 2004;62:644–647

PII: S1071-9091(05)00052-5

doi: 10.1016/j.spen.2005.04.002

Seminars in Pediatric Neurology
Volume 12, Issue 2 , Pages 119-131 , June 2005