Childs Nerv Syst (2015) 31:1401–1406 DOI 10.1007/s00381-015-2727-1
CASE REPORT
Hamartoma of the optic nerve in a young child—case report and review of the literature Malte Ottenhausen 1 & Petra Bittigau 2 & Arend Koch 3 & Erwin Lankes 4 & Matthias Schulz 1 & Ulrich W. Thomale 1,5
Received: 8 March 2015 / Accepted: 20 April 2015 / Published online: 30 April 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Purpose Hamartomas are well described but yet incompletely understood sporadic benign lesions that can arise in various locations. Hypothalamic hamartomas of infancy are often associated with severe developmental disturbances. We present a case of an infant boy with a hamartoma that arises from the optic nerve and lead to progressive unspecific seizure activity, behavioral problems and precautious puberty. Methods A 1-year-old male patient was presented with horizontal nystagmus and developmental retardation. Magnetic resonance imaging (MRI) with contrast revealed an isointense mass ventral of the chiasm consistent with a hamartoma. Soon after the MRI, the mother of the patient reported gelastic-like seizures. The patient was evaluated by an interdisciplinary team, and surgery was recommended. Intraoperatively, a firm attachment to the optic nerve was recognized and a thin remnant layer of tissue was left behind. Results After an uncomplicated near total resection, the patient improved significantly. After 6 months, the frequency of seizures reoccurred, which were again unresponsive to antiepileptic medication. In a second operation, a complete resection
* Ulrich W. Thomale [email protected] 1
Pediatric Neurosurgery, Charité Campus Virchow, Berlin, Germany
2
Department of Neuropediatrics, Charité Campus Virchow, Berlin, Germany
3
Department of Neuropathology, Charité Campus Mitte, Berlin, Germany
4
Department of Pediatric Endocrinology, Charité Campus Virchow Klinikum, Berlin, Germany
5
Pediatric Neurosurgery, Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
of the remnants was performed, and the patient showed lasting clinical improvement. Conclusion We conclude that hamartomas mimicking hypothalamic symptoms can also arise from the optic pathway and that a reoperation, if feasible, of even small remnants is essential in order to achieve lasting symptom relieve. Keywords Hamartoma . Optic nerve . Gelastic seizures
Introduction Hypothalamic hamartomas (HH) are of focal growth with disorganized neuronal tissue [1] with gliosis. They can arise from several structures like the mammillary bodies or the tuber cinereum and tend to grow similar to normal tissue [2]. There are two anatomical subtypes of HH, sessile (intrahypothalamic) and pedunculated (parahypothalamic) correlate with specific locations [3]. Typical symptoms include central precocious puberty (more common in pedunculated HH), epilepsy (hallmark symptom, often with gelastic seizures, more common in sessile HH) alongside developmental and psychological disturbances [4]. Although hamartomas are usually non-progressive, the symptoms lead to a significant decreased quality of life in children [5]. Especially when presenting with gelastic seizures early in life, the seizures tend to evolve over time and the clinical course is often detrimental leading to severe epileptic encephalopathy [2]. The presence of multiple types of seizure is not uncommon and well described in the literature [4, 6]. The patients also suffer frequently from behavioral disturbances like aggression and hyperactivity. Psychiatric comorbidities are also frequent. HH can be associated with congenital malformation syndromes or are seen sporadically. Notable, the sporadic HH tend to represent a more aggressive phenotype [2]. A Swedish study reported a prevalence of 0.5 per 100.000 [7]. MRI is the diagnostic tool
1402
of choice for HH, in which they visualize iso- or hypointense in T1 sequence and does not enhance after contrast [8]. Therapeutic options were extensively reviewed by Mittal et al. and consist of microsurgical resection, endoscopic disconnection (without resection), stereotactic radiosurgery, stereotactic radiofrequency ablation, deep brain stimulation, vagal nerve stimulation, frontal or temporal cortectomy, corpus callosotomy, and combinations of those options [9]. Although discussed controversially, currently complete surgical resection seems to be the best option if the HH is approachable at reasonable risk [10]. Because of the heterogeneity of symptoms and the low prevalence, patients and relatives often struggle before being diagnosed.
Case report Presentation A 1-year-old twin child was delivered via cesarean section in the 36th week of gestation (body weight 1630 g, APGAR: 9/8/9). He was now presented by his mother because of developmental delay as compared to his brother. She also described short episodes with gaze deviation and absence behavior that occurred multiple times daily. On initial examination a horizontal nystagmus, severe behavioral
Fig. 1 MRI-scans showing nonenhancing mass ventrobasal of the chiasm (arrows). a Axial T1weighted MRI with contrast. b Axial T2-weighted MRI. c Coronal T1-weighted MRI with contrast. d Sagittal T2-weighted MRI
Childs Nerv Syst (2015) 31:1401–1406
disturbances and an oversized phallus was noticed. Blood samples revealed elevated testosterone (4.72 nmol/l; normal range: 0.38–2.26), alpha-fetoprotein levels (60.7 μg/l; normal: 50 % significant reduction of seizures after reoperation Surgery Gamma knife radiosurgery Gamma knife radiosurgery Stereotactic radiosurgery Surgery and radiosurgery Retrospective study Prospective study Case report Case report Retrospective study Jayalakshmi et al. [13] Mathieu et al. [14] Unger et al. [15] Susheela et al. [17] Pati et al. [18]
6 4 2 1 21
Surgery Surgery and other N/A N/A Vagal nerve stimulation and surgery N/A Surgery Surgery Case series Cohort analysis Retrospective analysis Retrospective study Retrospective study Retrospective study Prospective study Case series Ng et al. [10] Park et al. [5] Coons et al. [1] Parvizi et al. [6] Brandberg et al. [7] Freeman et al. [8] Abla et al. [11] Li et al. [12]
4 21 57 100 12 72 10 3
Format Source
Number of cases Recent studies on hypothalamic hamartomas Table 1
progressive clinical course of these symptoms challenges the medical team to offer effective treatment options. The case presented here is a hamartoma arising from the optic nerve presenting with the classical symptoms of a peduncular HH. Because of the severe and fast progressing symptoms, we favored microsurgical resection due to a good approachable localization of the mass lesion. Several cohort studies were published presenting a positive effect of seizure control and with reasonable complication rates using open surgical approaches within recent years. Abla et al. reported a positive effect in 80 % (n=8) of treated patients with one half had 50 % seizure reduction rate and the other half was seizure free. The results correlated with the extent of resection [11]. Li et al. presented a long-term follow up (9–11 years) of three successfully operated cases without symptom recurrence [12]. Jayalakshmi et al. reported a favorable long-term outcome in 50 % (n=6) of their cases [13]. As alternative radiosurgery could have been applied with its limits to have long time neurocognitive side effects especially in the infant age group and it is known to have its therapeutic effect only with a delay of some months after treatment [14–16]. One recent study by Susheela et al. presented a case in which a decrease in seizure frequency was noticeable within days after treatment, with the patient further improving and being seizure free after 12 month [17]. Trials comparing radiosurgery and open surgical procedures have not been published yet. Table 1. provides an overview of similar publications.
Treatment
Fig. 5 Intraoperative picture (OPMI Pentero, Carl Zeiss Meditec AG, Germany) from the second surgery showing remnant tumor (arrow) attached to the optic nerve
Improvement in behavioral functioning Effective surgery results in favorable health-related quality of life Histopathological evaluation Neuroanatomical evaluation No therapeutic effect of vagal nerve stimulation Neuroimaging study Study on various surgical approaches. Seizure control correlates with GTR Surgical therapy can result in good long-term outcome of precocious puberty
1405
Results
Childs Nerv Syst (2015) 31:1401–1406
1406
Childs Nerv Syst (2015) 31:1401–1406
The first surgery was successful in terms of subtotal resection of the lesion as well as transient clinical improvement of the patient. However, after 6 months, the patient presented again with unspecific seizure activity and showed declining neurological status. Our decision to operate for the second time was based on the fact that the patient was in clear worsening condition and some minor remnant of the hamartoma was still present as seen in the MRI. Due to the fact that HH have intrinsic epileptogenicity, meaning epileptic seizures arise from the HH itself and that there may be some relation between the size of the HH and the severity of the seizures, we assumed that further reduction of the hamartoma could result in a reduction of the present seizure activity. Thereby taking the risk for the optic nerve was only secondary since no developmental improvement could be seen since the re-onset of the seizures. Our decision is supported by the promising results of second surgeries reported by Pati et al. in 2011 [18], who showed a reduction of seizures greater than 50 % in 67 % of their patients treated with repeated surgery.
2.
3.
4.
5.
6.
7.
8.
9.
Conclusion Although HH are benign lesions, their intrinsic epileptogenic activity and occurrence at the first stages of life causes treatment resistant forms of seizures alongside with endocrinological and psychiatric problems which can result in low quality of life for patients and their relatives. Therefore, unlike any other low-grade pediatric brain mass, early treatment should be performed if feasible at reasonable risks. As shown in the present case, hamartomas can arise from the optic nerve itself and cause the same symptoms as HH. When residual hamartoma is detected and symptoms are either remaining or even progressing, patients might benefit from a second operation.
10.
11.
12.
13.
14.
Conflict of interest The authors have no conflict of interest concerning the materials or methods used inthis report or the subsequent findings specified in the paper.
15.
16.
References 1.
Coons SW, Rekate HL, Prenger EC, Wang N, Drees C, Ng YT, Chung SS, Kerrigan JF (2007) The histopathology of hypothalamic hamartomas: study of 57 cases. J Neuropathol Exp Neurol 66: 131–141
17.
18.
Mittal S, Mittal M, Montes JL, Farmer JP, Andermann F (2013) Hypothalamic hamartomas. Part 1. Clinical, neuroimaging, and neurophysiological characteristics. Neurosurg Focus 34, E6 Kerrigan JF, Ng YT, Chung S, Rekate HL (2005) The hypothalamic hamartoma: a model of subcortical epileptogenesis and encephalopathy. Semin Pediatr Neurol 12:119–131 Pati S, Sollman M, Fife TD, Ng YT (2013) Diagnosis and management of epilepsy associated with hypothalamic hamartoma: an evidence-based systematic review. J Child Neurol 28:909–916 Park C, Wethe JV, Kerrigan JF (2013) Decreased quality of life in children with hypothalamic hamartoma and treatment-resistant epilepsy. J Child Neurol 28:50–55 Parvizi J, Le S, Foster BL, Bourgeois B, Riviello JJ, Prenger E, Saper C, Kerrigan JF (2011) Gelastic epilepsy and hypothalamic hamartomas: neuroanatomical analysis of brain lesions in 100 patients. Brain J Neurol 134:2960–2968 Brandberg G, Raininko R, Eeg-Olofsson O (2004) Hypothalamic hamartoma with gelastic seizures in Swedish children and adolescents. Eur J Paediatr Neurol EJPN Off J Eur Paediatr Neurol Soc 8: 35–44 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 25:450–462 Mittal S, Mittal M, Montes JL, Farmer JP, Andermann F (2013) Hypothalamic hamartomas. Part 2. Surgical considerations and outcome. Neurosurg Focus 34, E7 Ng YT, Hastriter EV, Wethe J, Chapman KE, Prenger EC, Prigatano GP, Oppenheim T, Varland M, Rekate HL, Kerrigan JF (2011) Surgical resection of hypothalamic hamartomas for severe behavioral symptoms. Epilepsy Behav E&B 20:75–78 Abla AA, Rekate HL, Wilson DA, Wait SD, Uschold TD, Prenger E, Ng YT, Nakaji P, Kerrigan JF (2011) Orbitozygomatic resection for hypothalamic hamartoma and epilepsy: patient selection and outcome. Childs Nerv Syst ChNS Off J Int Soc Pediatr Neurosurg 27:265–277 Li CD, Luo SQ, Gong J, Ma ZY, Jia G, Zhang YQ, Li JF (2013) Surgical treatment of hypothalamic hamartoma causing central precocious puberty: long-term follow-up. J Neurosurg Pediatr 12: 151–154 Jayalakshmi S, Panigrahi M, Reddy R, Somayajula S (2014) Clinical characteristics and long-term outcome of surgery for hypothalamic hamartoma in children with refractory epilepsy. Ann Indian Acad Neurol 17:43–47 Mathieu D, Kondziolka D, Niranjan A, Flickinger J, Lunsford LD (2006) Gamma knife radiosurgery for refractory epilepsy caused by hypothalamic hamartomas. Stereotact Funct Neurosurg 84:82–87 Unger F, Schrottner O, Haselsberger K, Korner E, Ploier R, Pendl G (2000) Gamma knife radiosurgery for hypothalamic hamartomas in patients with medically intractable epilepsy and precocious puberty. Report of two cases. J Neurosurg 92:726–731 Romanelli P, Muacevic A, Striano S (2008) Radiosurgery for hypothalamic hamartomas. Neurosurg Focus 24, E9 Susheela SP, Revannasiddaiah S, Mallarajapatna GJ, Basavalingaiah A (2013) Robotic-arm stereotactic radiosurgery as a definitive treatment for gelastic epilepsy associated with hypothalamic hamartoma. BMJ Case Rep 2013 Pati S, Abla AA, Rekate HL, Ng YT (2011) Repeat surgery for hypothalamic hamartoma in refractory epilepsy. Neurosurg Focus 30, E3
CASE REPORT
Hamartoma of the optic nerve in a young child—case report and review of the literature Malte Ottenhausen 1 & Petra Bittigau 2 & Arend Koch 3 & Erwin Lankes 4 & Matthias Schulz 1 & Ulrich W. Thomale 1,5
Received: 8 March 2015 / Accepted: 20 April 2015 / Published online: 30 April 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Purpose Hamartomas are well described but yet incompletely understood sporadic benign lesions that can arise in various locations. Hypothalamic hamartomas of infancy are often associated with severe developmental disturbances. We present a case of an infant boy with a hamartoma that arises from the optic nerve and lead to progressive unspecific seizure activity, behavioral problems and precautious puberty. Methods A 1-year-old male patient was presented with horizontal nystagmus and developmental retardation. Magnetic resonance imaging (MRI) with contrast revealed an isointense mass ventral of the chiasm consistent with a hamartoma. Soon after the MRI, the mother of the patient reported gelastic-like seizures. The patient was evaluated by an interdisciplinary team, and surgery was recommended. Intraoperatively, a firm attachment to the optic nerve was recognized and a thin remnant layer of tissue was left behind. Results After an uncomplicated near total resection, the patient improved significantly. After 6 months, the frequency of seizures reoccurred, which were again unresponsive to antiepileptic medication. In a second operation, a complete resection
* Ulrich W. Thomale [email protected] 1
Pediatric Neurosurgery, Charité Campus Virchow, Berlin, Germany
2
Department of Neuropediatrics, Charité Campus Virchow, Berlin, Germany
3
Department of Neuropathology, Charité Campus Mitte, Berlin, Germany
4
Department of Pediatric Endocrinology, Charité Campus Virchow Klinikum, Berlin, Germany
5
Pediatric Neurosurgery, Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
of the remnants was performed, and the patient showed lasting clinical improvement. Conclusion We conclude that hamartomas mimicking hypothalamic symptoms can also arise from the optic pathway and that a reoperation, if feasible, of even small remnants is essential in order to achieve lasting symptom relieve. Keywords Hamartoma . Optic nerve . Gelastic seizures
Introduction Hypothalamic hamartomas (HH) are of focal growth with disorganized neuronal tissue [1] with gliosis. They can arise from several structures like the mammillary bodies or the tuber cinereum and tend to grow similar to normal tissue [2]. There are two anatomical subtypes of HH, sessile (intrahypothalamic) and pedunculated (parahypothalamic) correlate with specific locations [3]. Typical symptoms include central precocious puberty (more common in pedunculated HH), epilepsy (hallmark symptom, often with gelastic seizures, more common in sessile HH) alongside developmental and psychological disturbances [4]. Although hamartomas are usually non-progressive, the symptoms lead to a significant decreased quality of life in children [5]. Especially when presenting with gelastic seizures early in life, the seizures tend to evolve over time and the clinical course is often detrimental leading to severe epileptic encephalopathy [2]. The presence of multiple types of seizure is not uncommon and well described in the literature [4, 6]. The patients also suffer frequently from behavioral disturbances like aggression and hyperactivity. Psychiatric comorbidities are also frequent. HH can be associated with congenital malformation syndromes or are seen sporadically. Notable, the sporadic HH tend to represent a more aggressive phenotype [2]. A Swedish study reported a prevalence of 0.5 per 100.000 [7]. MRI is the diagnostic tool
1402
of choice for HH, in which they visualize iso- or hypointense in T1 sequence and does not enhance after contrast [8]. Therapeutic options were extensively reviewed by Mittal et al. and consist of microsurgical resection, endoscopic disconnection (without resection), stereotactic radiosurgery, stereotactic radiofrequency ablation, deep brain stimulation, vagal nerve stimulation, frontal or temporal cortectomy, corpus callosotomy, and combinations of those options [9]. Although discussed controversially, currently complete surgical resection seems to be the best option if the HH is approachable at reasonable risk [10]. Because of the heterogeneity of symptoms and the low prevalence, patients and relatives often struggle before being diagnosed.
Case report Presentation A 1-year-old twin child was delivered via cesarean section in the 36th week of gestation (body weight 1630 g, APGAR: 9/8/9). He was now presented by his mother because of developmental delay as compared to his brother. She also described short episodes with gaze deviation and absence behavior that occurred multiple times daily. On initial examination a horizontal nystagmus, severe behavioral
Fig. 1 MRI-scans showing nonenhancing mass ventrobasal of the chiasm (arrows). a Axial T1weighted MRI with contrast. b Axial T2-weighted MRI. c Coronal T1-weighted MRI with contrast. d Sagittal T2-weighted MRI
Childs Nerv Syst (2015) 31:1401–1406
disturbances and an oversized phallus was noticed. Blood samples revealed elevated testosterone (4.72 nmol/l; normal range: 0.38–2.26), alpha-fetoprotein levels (60.7 μg/l; normal: 50 % significant reduction of seizures after reoperation Surgery Gamma knife radiosurgery Gamma knife radiosurgery Stereotactic radiosurgery Surgery and radiosurgery Retrospective study Prospective study Case report Case report Retrospective study Jayalakshmi et al. [13] Mathieu et al. [14] Unger et al. [15] Susheela et al. [17] Pati et al. [18]
6 4 2 1 21
Surgery Surgery and other N/A N/A Vagal nerve stimulation and surgery N/A Surgery Surgery Case series Cohort analysis Retrospective analysis Retrospective study Retrospective study Retrospective study Prospective study Case series Ng et al. [10] Park et al. [5] Coons et al. [1] Parvizi et al. [6] Brandberg et al. [7] Freeman et al. [8] Abla et al. [11] Li et al. [12]
4 21 57 100 12 72 10 3
Format Source
Number of cases Recent studies on hypothalamic hamartomas Table 1
progressive clinical course of these symptoms challenges the medical team to offer effective treatment options. The case presented here is a hamartoma arising from the optic nerve presenting with the classical symptoms of a peduncular HH. Because of the severe and fast progressing symptoms, we favored microsurgical resection due to a good approachable localization of the mass lesion. Several cohort studies were published presenting a positive effect of seizure control and with reasonable complication rates using open surgical approaches within recent years. Abla et al. reported a positive effect in 80 % (n=8) of treated patients with one half had 50 % seizure reduction rate and the other half was seizure free. The results correlated with the extent of resection [11]. Li et al. presented a long-term follow up (9–11 years) of three successfully operated cases without symptom recurrence [12]. Jayalakshmi et al. reported a favorable long-term outcome in 50 % (n=6) of their cases [13]. As alternative radiosurgery could have been applied with its limits to have long time neurocognitive side effects especially in the infant age group and it is known to have its therapeutic effect only with a delay of some months after treatment [14–16]. One recent study by Susheela et al. presented a case in which a decrease in seizure frequency was noticeable within days after treatment, with the patient further improving and being seizure free after 12 month [17]. Trials comparing radiosurgery and open surgical procedures have not been published yet. Table 1. provides an overview of similar publications.
Treatment
Fig. 5 Intraoperative picture (OPMI Pentero, Carl Zeiss Meditec AG, Germany) from the second surgery showing remnant tumor (arrow) attached to the optic nerve
Improvement in behavioral functioning Effective surgery results in favorable health-related quality of life Histopathological evaluation Neuroanatomical evaluation No therapeutic effect of vagal nerve stimulation Neuroimaging study Study on various surgical approaches. Seizure control correlates with GTR Surgical therapy can result in good long-term outcome of precocious puberty
1405
Results
Childs Nerv Syst (2015) 31:1401–1406
1406
Childs Nerv Syst (2015) 31:1401–1406
The first surgery was successful in terms of subtotal resection of the lesion as well as transient clinical improvement of the patient. However, after 6 months, the patient presented again with unspecific seizure activity and showed declining neurological status. Our decision to operate for the second time was based on the fact that the patient was in clear worsening condition and some minor remnant of the hamartoma was still present as seen in the MRI. Due to the fact that HH have intrinsic epileptogenicity, meaning epileptic seizures arise from the HH itself and that there may be some relation between the size of the HH and the severity of the seizures, we assumed that further reduction of the hamartoma could result in a reduction of the present seizure activity. Thereby taking the risk for the optic nerve was only secondary since no developmental improvement could be seen since the re-onset of the seizures. Our decision is supported by the promising results of second surgeries reported by Pati et al. in 2011 [18], who showed a reduction of seizures greater than 50 % in 67 % of their patients treated with repeated surgery.
2.
3.
4.
5.
6.
7.
8.
9.
Conclusion Although HH are benign lesions, their intrinsic epileptogenic activity and occurrence at the first stages of life causes treatment resistant forms of seizures alongside with endocrinological and psychiatric problems which can result in low quality of life for patients and their relatives. Therefore, unlike any other low-grade pediatric brain mass, early treatment should be performed if feasible at reasonable risks. As shown in the present case, hamartomas can arise from the optic nerve itself and cause the same symptoms as HH. When residual hamartoma is detected and symptoms are either remaining or even progressing, patients might benefit from a second operation.
10.
11.
12.
13.
14.
Conflict of interest The authors have no conflict of interest concerning the materials or methods used inthis report or the subsequent findings specified in the paper.
15.
16.
References 1.
Coons SW, Rekate HL, Prenger EC, Wang N, Drees C, Ng YT, Chung SS, Kerrigan JF (2007) The histopathology of hypothalamic hamartomas: study of 57 cases. J Neuropathol Exp Neurol 66: 131–141
17.
18.
Mittal S, Mittal M, Montes JL, Farmer JP, Andermann F (2013) Hypothalamic hamartomas. Part 1. Clinical, neuroimaging, and neurophysiological characteristics. Neurosurg Focus 34, E6 Kerrigan JF, Ng YT, Chung S, Rekate HL (2005) The hypothalamic hamartoma: a model of subcortical epileptogenesis and encephalopathy. Semin Pediatr Neurol 12:119–131 Pati S, Sollman M, Fife TD, Ng YT (2013) Diagnosis and management of epilepsy associated with hypothalamic hamartoma: an evidence-based systematic review. J Child Neurol 28:909–916 Park C, Wethe JV, Kerrigan JF (2013) Decreased quality of life in children with hypothalamic hamartoma and treatment-resistant epilepsy. J Child Neurol 28:50–55 Parvizi J, Le S, Foster BL, Bourgeois B, Riviello JJ, Prenger E, Saper C, Kerrigan JF (2011) Gelastic epilepsy and hypothalamic hamartomas: neuroanatomical analysis of brain lesions in 100 patients. Brain J Neurol 134:2960–2968 Brandberg G, Raininko R, Eeg-Olofsson O (2004) Hypothalamic hamartoma with gelastic seizures in Swedish children and adolescents. Eur J Paediatr Neurol EJPN Off J Eur Paediatr Neurol Soc 8: 35–44 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 25:450–462 Mittal S, Mittal M, Montes JL, Farmer JP, Andermann F (2013) Hypothalamic hamartomas. Part 2. Surgical considerations and outcome. Neurosurg Focus 34, E7 Ng YT, Hastriter EV, Wethe J, Chapman KE, Prenger EC, Prigatano GP, Oppenheim T, Varland M, Rekate HL, Kerrigan JF (2011) Surgical resection of hypothalamic hamartomas for severe behavioral symptoms. Epilepsy Behav E&B 20:75–78 Abla AA, Rekate HL, Wilson DA, Wait SD, Uschold TD, Prenger E, Ng YT, Nakaji P, Kerrigan JF (2011) Orbitozygomatic resection for hypothalamic hamartoma and epilepsy: patient selection and outcome. Childs Nerv Syst ChNS Off J Int Soc Pediatr Neurosurg 27:265–277 Li CD, Luo SQ, Gong J, Ma ZY, Jia G, Zhang YQ, Li JF (2013) Surgical treatment of hypothalamic hamartoma causing central precocious puberty: long-term follow-up. J Neurosurg Pediatr 12: 151–154 Jayalakshmi S, Panigrahi M, Reddy R, Somayajula S (2014) Clinical characteristics and long-term outcome of surgery for hypothalamic hamartoma in children with refractory epilepsy. Ann Indian Acad Neurol 17:43–47 Mathieu D, Kondziolka D, Niranjan A, Flickinger J, Lunsford LD (2006) Gamma knife radiosurgery for refractory epilepsy caused by hypothalamic hamartomas. Stereotact Funct Neurosurg 84:82–87 Unger F, Schrottner O, Haselsberger K, Korner E, Ploier R, Pendl G (2000) Gamma knife radiosurgery for hypothalamic hamartomas in patients with medically intractable epilepsy and precocious puberty. Report of two cases. J Neurosurg 92:726–731 Romanelli P, Muacevic A, Striano S (2008) Radiosurgery for hypothalamic hamartomas. Neurosurg Focus 24, E9 Susheela SP, Revannasiddaiah S, Mallarajapatna GJ, Basavalingaiah A (2013) Robotic-arm stereotactic radiosurgery as a definitive treatment for gelastic epilepsy associated with hypothalamic hamartoma. BMJ Case Rep 2013 Pati S, Abla AA, Rekate HL, Ng YT (2011) Repeat surgery for hypothalamic hamartoma in refractory epilepsy. Neurosurg Focus 30, E3
