Hypothalamic hamartoma presenting as central precocious puberty: a rare case report

Precocious puberty is defined as children attaining puberty more than 2.5 to 3 standard deviations (SD) earlier than the median age, or before the age of eight years in girls and nine years in boys. Hypothalamic hamartoma (HH) are rare, non progressive tumor like malformation. Precocious puberty due to HH occurs particularly at early ages, even 2 or 3 years. Treatment options for isolated CPP due to HH include GnRH analogs agonists continuously stimulates pituitary gonadotrophs, which further help in decreasing and desensitizing the release of LH, and to a lesser extent, FSH till the time puberty naturally set in. We present a case of precocious puberty due to hypothalamic hamartoma in 3 years old girl. Treated with GnRH analog lupirode and responded well to treatment with cessation of menstruation and reduction in breast size.

Endoscopic Treatment of Hypothalamic Hamartomas

Hypothalamic hamartoma (HH) is a benign indolent lesion despite the presentation of refractory epilepsy. Behavioral disturbances and endocrine problems are additional critical symptoms that arise along with HHs. Due to its nature of generating epileptiform discharge and spreading to cortical region, various management strategies have been proposed and combined. Surgical approaches with open craniotomy or endoscopy, stereotactic approaches with radiosurgery and gamma knife surgery or radiofrequency thermos-coagulation, and laser ablation have been introduced. Topographical dimension and the surgeon’s preference are key factors for treatment modalities. Endoscopic disconnection has been one of the most favorable options performed in treating HHs. Here we discuss presurgical evaluation, patient selection, surgical procedures, and complications.

An 11-month-old girl with central precocious puberty caused by hypothalamic hamartoma

Central precocious puberty (CPP) is caused by premature activation of the hypothalamic-gonadal axis, and must be treated adequately. In particular, CPP that occurs at a relatively young age or in boys is likely to be caused by an organic lesion. Hypothalamic hamartoma (HH) is the most common organic cause of CPP. The present case report describes an 11-month-old female infant who presented with vaginal bleeding and rapidly progressive secondary sex characteristics from the age of 6 months. She was diagnosed with CPP following the detection of HH via magnetic resonance imaging. The infant girl was successfully treated with gonadotropin-releasing hormone agonist. After 6 months, her breast had regressed and clinical and radiological follow-up demonstrated stable findings with no evidence of tumor growth or secondary sexual characteristics until the fourth year after the initiation of treatment. This patient is the one of the youngest infants presenting with CPP and HH in Korea; treatment was successful over a relatively long follow-up period.

An 11-month-old girl with central precocious puberty caused by hypothalamic hamartoma

Central precocious puberty (CPP) is caused by premature activation of the hypothalamic-gonadal axis, and must be treated adequately. In particular, CPP that occurs at a relatively young age or in boys is likely to be caused by an organic lesion. Hypothalamic hamartoma (HH) is the most common organic cause of CPP. The present case report describes an 11-month-old female infant who presented with vaginal bleeding and rapidly progressive secondary sex characteristics from the age of 6 months. She was diagnosed with CPP following the detection of HH via magnetic resonance imaging. The infant girl was successfully treated with gonadotropin-releasing hormone agonist. After 6 months, her breast had regressed and clinical and radiological follow-up demonstrated stable findings with no evidence of tumor growth or secondary sexual characteristics until the fourth year after the initiation of treatment. This patient is the one of the youngest infants presenting with CPP and HH in Korea; treatment was successful over a relatively long follow-up period.

Rehabilitation for Cerebral Palsy Complicated with Hypothalamic Hamartoma: A Case Report / 中国康复理论与实践

@#Objective To study the rehabilitation for cerebral palsy combined with hypothalamic hamartoma. Methods A case accepting rehabilitation over 4 years was reviewed, especially the body length, body mass, bone age, hormone levels, the scores of Gross Motor Func-tion Measure (GMFM) and 0 to 6 Years Old Children's Neuropsychological Examination. Results After treatment of inhibitory precocious puberty and rehabilitation training, the body length, body mass, bone age, hormone levels, scores of GMFM and 0 to 6 Years Old Children's Neuropsychological Examination improved. Since epilepsy at the recent time, her motor, response and emotional control declined. Conclu-sion For similar cases, it is necessary to regularly review, to find problems and adjust the treatment and rehabilitation program in time.

Etiology and clinical characteristics of 30 children with tumor-associated precocity / 中华实用儿科临床杂志

Objective To analyze the etiology and clinical characteristics of children with tumor-associated precocity.Methods Thirty children with tumor-associated precocity hospitalized in Department of Surgery of Beijing Children's Hospital Affiliated to Capital Medical University from Jan.2006 to Mar.2012 were selected as research subjects.The causes,clinical characteristics and treatment situation of the patients were retrospectively studied.Results The group of patients included 14 boys and 16 girls,with average age of (3.74 ± 2.44) years.Twenty-two patients (73.3％) were younger than 5 years old,and their etiological distributions listed as follows:8 cases were hypothalamic hamartoma(HH),2 cases were hypothalamic germinoma,1 case was arachnoid cyst,7 cases were adrenocortical tumor (in which 1 case was adenoma and 6 cases were adenocacinoma respectively),5 cases were ovarian cyst,2 cases were ovarian tumor (in which 1 case was endodermal sinus tumor and 1 case was sex cord-stromal tumor respectively),2 cases were MuCune-Albright syndrome,and 1 case was mediastinal teratoma,1 case was penis primitive neuroectoderm tumor,and 1 case was Leydig cell proliferation accompanied with neoplasma.Eleven patients(36.7％) suffered central precocious puberty,with HH (n =8) being the most common causes.Four patients with HH presented with gelastic epilepsy.Precocious puberty caused by HH patients could be safely controlled by gonadotropin-releasing hormone agonists.Nineteen patients(63.3％) suffered peripheral precocious puberty,with adrenocortical tumor being the most common cause for the boys and ovarian cyst being the most common cause for the girls.Besides that,the onset symptom of a patient with adenocacinoma was facial acne accompanied with hypertrichiasis and another patient with ovarian tumor had intermittent abdominal pain,and the onset symptoms of all the boys were external genital development and those of the girls were mammary development or colporrhagia,respectively.Conclusions Tumors are one of the most causes of precocious puberty in children.During the process of diagnosis and treatment of precocious puberty,imaging examinations on pituitary,gonad and adrenal gland should be paid great attention to and seldom occurred tumors should also be considered.For ovarian cyst patients with precocious puberty attention shall be paid attention to the differentiation from MuCune-Albright syndrome.

Clinical Manifestations and Treatment of Hypothalamic Hamartoma

PURPOSE: The aim of this study was to describe the clinical manifestations and radiologic characteristics of patients with hypothalamic hamartoma (HH) and to delineate various treatment modalities.METHODS: We retrospectively reviewed the medical records of 11 patients with HH at Samsung Seoul Hospital between 1997 and 2013.RESULTS: Mean age of diagnosis was 2.7 years. Seven patients had intractable epilepsy, seven exhibited precocious puberty, and four had both. Gelastic seizure was the most common seizure and was intractable to medications. The patients with the intrahypothalamic type (18.2%) had no precocious puberty, while those with the parahypothalamic type (36.4%) didn't have seizures. Patients (n=6) with intractable epilepsy underwent gamma-knife radiosurgery (GKS); five of these patients responded to this treatment.CONCLUSIONS: The most frequent presenting symptoms of HH were gelastic seizure and precocious puberty. The location and size of tumor defined by brain magnetic resonance imaging affected presenting symptoms and the selection of surgical treatment. GKS can be considered if the patients showed intractable epilepsy and the size of tumor is less than 2 cm in diameter.

Clinical Manifestations and Treatment of Hypothalamic Hamartoma / 대한간질학회지

PURPOSE: The aim of this study was to describe the clinical manifestations and radiologic characteristics of patients with hypothalamic hamartoma (HH) and to delineate various treatment modalities. METHODS: We retrospectively reviewed the medical records of 11 patients with HH at Samsung Seoul Hospital between 1997 and 2013. RESULTS: Mean age of diagnosis was 2.7 years. Seven patients had intractable epilepsy, seven exhibited precocious puberty, and four had both. Gelastic seizure was the most common seizure and was intractable to medications. The patients with the intrahypothalamic type (18.2%) had no precocious puberty, while those with the parahypothalamic type (36.4%) didn't have seizures. Patients (n=6) with intractable epilepsy underwent gamma-knife radiosurgery (GKS); five of these patients responded to this treatment. CONCLUSIONS: The most frequent presenting symptoms of HH were gelastic seizure and precocious puberty. The location and size of tumor defined by brain magnetic resonance imaging affected presenting symptoms and the selection of surgical treatment. GKS can be considered if the patients showed intractable epilepsy and the size of tumor is less than 2 cm in diameter.

Challenges in the surgical treatment of epilepsy: hypothalamic hamartoma in infancy - case report / Desafios no tratamento cirúrgico das epilepsias: hamartoma hipotalâmico na infância - relato de caso

INTRODUCTION: Hypothalamic hamartoma is a rare congenital malformation, characterized by epilepsy, especially gelastic seizures, psychomotor developmental delay, mental retardation, behavioral disorders and precocious puberty. Epilepsy has early onset and is usually medically refractory. Etiology and pathophysiological mechanisms are unclear. The EEG can present disorganization and slowing of background activity and multifocal and/or generalized epileptogenic discharges. OBJECTIVE: To report the difficulties and challenges of neurosurgical treatment of a hypothalamic hamartoma in an infant. CASE REPORT: Infant with seizures since eight months old of age. The neurological investigation revealed a lesion in tuber cinereum suggestive of hamartoma. The epilepsy evolved with resistance to antiepileptic drugs, requiring neurosurgical procedure. The endoscopic resection could not be performed because the hamartoma was firmly attached to the hypothalamus. Currently, the child remains with tonic, clonic and atonic seizures. DISCUSSION: Lesionectomy performed by microsurgery or radiosurgery seems to be the most effective treatment for seizure control in patients with hypothalamic hamartomas who do not respond to clinical treatment. Callosotomy may be effective in selected cases, and lobectomy/cortical resections are not related to seizure control. In some patients, particularly in infants, lesionectomy and radiosurgery may be technically unfeasible.

INTRODUÇÃO: hamartoma hipotalâmico é uma malformação congênita rara, que pode se manifestar através de crises epilépticas, principalmente as gelásticas, atraso do desenvolvimento neuropsicomotor, retardo mental, distúrbios comportamentais e puberdade precoce. As crises têm início precoce e são clinicamente refratárias. A etiologia e os mecanismos fisiopatogênicos não são totalmente conhecidos. O eletrencefalograma pode apresentar desde desorganização e alentecimento da atividade de base até paroxismos epileptogênicos multifocais e/ou generalizados. OBJETIVO: relatar as dificuldades e desafios do tratamento neurocirúrgico em um caso de hamartoma hipotalâmico em um lactente. RELATO DO CASO: lactente com crises epilépticas desde oito meses de idade. A investigação revelou a presença de uma lesão em túber cinerium sugestiva de hamartoma. As crises tornaram-se refratárias, sendo indicado procedimento cirúrgico. A ressecção endoscópica não pôde ser realizada, pois o hamartoma encontrava-se totalmente aderido ao hipotálamo. Atualmente, a criança mantém crises tônicas, clônicas e atônicas. DISCUSSÃO: a lesionectomia realizada por microcirurgia ou radiocirurgia parece ser o tratamento mais efetivo para o controle das crises em pacientes com hamartoma hipotalâmico. Calosotomia pode ser eficaz em casos selecionados e lobectomias/ressecções corticais não tem efetividade no controle das crises. Em alguns pacientes, particularmente nos lactentes, lesionectomia e radiocirurgia podem ser tecnicamente inviáveis. Quando o tratamento neurocirúrgico não é possível a epilepsia deve ser classificada como intratável.

Estudo dos genes TTF-1 e EAP1 em pacientes com distúrbios puberais centrais e avaliação neurológica e neurocognitiva de pacientes com hamartoma hipotalâmico / Analysis of TTF-1 and EAP1 genes in patients with central pubertal disorders and neurologic and neurocognitive evaluation of patients with hypothalamic hamartoma

O mecanismo de controle da secreção de GnRH inclui diversas vias neuronais. Estudos em modelos animais identificaram genes que codificam fatores de transcrição, tais como TTF-1 (thyroid transcription factor 1) e EAP1 (enhanced at puberty), que atuam no controle transcricional de genes codificadores de fatores excitatórios (KiSS1 e GnRH) e inibitórios (preproencefalinas) regulando a secreção de GnRH. Em primatas, a expressão de EAP1 e TTF-1 aumenta, no início da puberdade, nas regiões hipotalâmicas envolvidas na secreção de GnRH. Nos modelos animais, a deleção pós-natal de TTF-1 e o silenciamento do EAP1 provocam atraso puberal e prejuízo na função reprodutiva. TTF-1 também está envolvido na morfogênese diencefálica, por meio da via de sinalização da família Sonic-Hedgehog. Anormalidades na secreção de GnRH resultam em distúrbios puberais, que variam de puberdade precoce central (PPC) a hipogonadismo hipogonadotrófico. Hipotetizamos que anormalidades genéticas no TTF-1 e EAP1 estejam envolvidas na patogênese dos distúrbios puberais centrais. A PPC pode ser idiopática ou devido a causas orgânicas, sendo o hamartoma hipotalâmico, uma malformação congênita não neoplásica, a mais conhecida. Os pacientes com PPC devido a hamartoma hipotalâmico podem cursar com alterações neurológicas e cognitivas. Nossos objetivos foram: estudar as regiões codificadora do TTF-1 e do EAP1 e a região promotora do TTF-1 em pacientes com distúrbios puberais centrais; estabelecer a prevalência, taxa de penetrância e modo de herança da forma familial de PPC e caracterizar as manifestações neurológicas e neurocognitivas de pacientes com PPC devido a hamartoma hipotalâmico. Foram selecionados 133 pacientes com distúrbios puberais centrais - PPC idiopática (n=71), PPC devido a hamartoma hipotalâmico (n=15) e hipogonadismo hipogonadotrópico isolado normósmico (HHIn) (n=47) - e controles (n=53). Os genes TTF-1 e EAP1 foram amplificados e submetidos a sequenciamento automático. Os tratos...

GnRH secretion control involves multiple neuronal pathways. Animal studies have identified genes which codifies transcription factors, such as TTF-1 (thyroid transcription factor 1) and EAP1 (enhanced at puberty), that act in the transcriptional control of genes that codifies excitatory (KiSS1 and GnRH) and inhibitory factors (preproenkephalines) regulating GnRH secretion. In nonhuman primates, expression of EAP1 and TTF-1 are increased at the hypothalamic regions involved in GnRH secretion, at the beginning of puberty. In animal models, post-natal TTF-1 deletion and silencing of EAP1 lead to pubertal delay and damage of reproductive function. TTF-1 is also involved in diencephalic morphogenesis, through signalization via Sonic-Hedgehog family. Abnormalities in GnRH secretion are responsible for pubertal disorders, varying from central precocious puberty (CPP) to hypogonadotropic hypogonadism. We hypothesized that genetic anomalies at TTF-1 and EAP1 are involved in the pathogenesis of central pubertal disorders. CPP may be idiopathic or due to organic alterations and hypothalamic hamartoma, a non-neoplasic congenital malformation, is the most frequent known organic cause. Patients with CPP due to hypothalamic hamartoma may have neurological and cognitive disfunctions. Our aims were: to evaluated the codifying region of TTF-1 and EAP1 and the promoter region of TTF-1 in patients with central pubertal disorders; to establish the prevalence, penetrance rate and inheritance mode of familial CPP and to characterize neurologic and neurocognitive aspects of patients with CPP due to hypothalamic hamartoma. We selected 133 patients with central pubertal disorders idiopathic CPP (n=71), CPP due to hypothalamic hamartoma (n=15) and normosmic isolated hypogonadropic hypogonadism (nIHH) (n=47) - and controls (n=53). TTF-1 and EAP1 genes were amplified and sequenced. Polyglutamine and polyalanine tracts of EAP1 were studied by a fragment size analyser software...

Current Source Analysis of Interictal Spikes in Two Patients With Gelastic Epilepsy-Hypothalamic Hamartoma Syndrome

BACKGROUND: Interictal spikes in gelastic epilepsy-hypothalamic hamartoma syndrome are mainly in the fronto-temporal area. Current source analysis of the interictal spikes has not been done enough. We tried the current source analysis in 2 patients with gelastic epilepsy-hypothalamic hamartoma syndrome using both of the discrete and distributed models. METHODS: Twenty 1 sec epochs including the negative peak of the spikes, were selected from one or two electroencephalographic recordings respectively in each patient. These 20 epochs were averaged into a single spike. The current dipole sources of the averaged spike were analyzed and located on a spherical head model. The current source density of the negative peak point of the averaged spike was located on the Talairach human brain map. RESULTS: The current dipole sources were in the right subcallosal gyrus, or the right or left anterior cingulate gyri. The current source density was distributed in the bilateral medial frontal area including the anterior cingulate gyri. CONCLUSIONS: The interictal spikes of patients with gelastic epilepsy-hypothalamic hamartoma syndrome may be generated by the current sources located in the bilateral medial frontal area.

Gamma Knife Radiosurgery in Patients with a Hypothalamic Hamartoma Associated with Intractable Gelastic Epilepsy: Report of Three Cases

Hypothalamic hamartoma(HH) is an unusual nonneoplastic developmental lesion associated with gelastic epilepsy and precocious puberty, mostly found in children. Although open surgery has been attempted when antiepileptic medication failed to control seizures, its deep location and surrounding vital structures often rendered surgery unsuccessful. We describe the outcome of gamma knife radiosurgery in three children with a HH associated with gelastic epilepsy and reviewed the literature for a possible therapeutic mechanism.

An Experience of Gamma Knife Radiosurgery for Hypothalamic Hamartoma with Gelastic Seizure / 대한간질학회지

We report a 12 year-old girl patient with hypothalmic hamartoma presented a gelastic seizure for 11 years. On magnetic resonance images, a 10.5 mm-sized mass was detected that was originated from the tuber cinereum into the third ventricle. This mass was isosignal intensity on T1WI, slightly high signal intensity on T2WI and not enhanced with Gadolinium. On interictal EEG, the frequent spike or polyspike dischage was recorded from the left fronto-central area. On ictal EEG, the suspicious polyspike dischages followed by spike and wave discharge were recorded from the left or both fronto-central or fronto-centro-temporal area. On 18-FDG PET (18-fluorodeoxyglucose positron emission tomography), the glucose metabolism was decresed on the mass. We treated this lesion using gamma knife radiosurgery (18 Gy at 50% margin, 508.2 mm3 volume). After 6 months, the frequency of gelastic seizure was decreased.

Gamma knife radiosurgery for hypothalamic hamartomas / 第三军医大学学报

Objective To investigate the treatment effect of gamma knife radiosurgery for hypothalamic hamartomas. Methods Gamma knife radiosurgery was performed in 9 patients with gelastic seizures. Collimator helmets (4 and 8 mm) were used and a radiosurgery plan was designed to cover 90% of the hamartoma at the 40%~55% isodose curve with the center dose of 28~40 Gy and the margin dose of 12~18 Gy. The clinical outcome was evaluated with the Tan’s scale. Results No complications due to gamma knife radiosurgery occurred. A follow-up from 24 to 54 months showed effectiveness in 7 patients, disappearance of seizure in 1 patient, rare occurrence in 3 patients, significantly reduced occurrence in 2 patients, improvement in seizure control in 1 patient, but ineffectiveness in 2 patients. Conclusion As an approach to the treatment of hypothalamic hamartomas, gamma knife is a safe and cost-effective therapy with rare side effects for hypothalamic harmatomas.

Treatment of Hypothalamic Hamartoma

This study presents seven patients with hypothalamic hamartomas diagnosed on the basis of MRI. Histological confirmation was performed in one patient who underwent surgery. Four patients presented with epilepsy, including gelastic seizures. Other symptoms were behavior abnormalities in 3 patients and precocious puberty in 4 patients. We classify hypothalamic hamartomas into four subgroups according to MRI finding: Types la lesions were less than 100mm in lesions less than 10mm and mammillary body. Type lla lesions were more than 100mm in diamenter and sessilely attached to hypothalamus with slight hypothalmic displacement and Type llb lesions more than 10mm and with marked displacement of hypothalamus. We could achieve good result with surgical resection in one patient with Type llb hamartoma associated with gelastic seizure that was unresponsive to medical treatment. We performed gamma knife radiosurgery in three patients with gelastic seizue(2 patients with Type lla and 1 patient with Type llb) and three patients with precocious puberty(2 patients with Type la and 1 patient with Type lla 1 patient with Type llb) and three patients with precocious puberty(2 patients with Type la and 1 patient with type lb). The authors propose direct surgery as a treatment for this progressive syndrome and gamma knife radiourgery is alternative treatment for high risk patients.

A Case of Spinal Epidural Hematoma due to Arteriovenous Malformation

Spinal epidural hematoma results from various causes such as use of anticoagulants, hemorrhagic diathesis, pregnancy, labor, arteriovenous malformation and spinal anesthesia as well as idiopathic orgin. We report a 3-year-old boy who was found to have spinal epidural hematoma and presented with lower back pain and fever. He developed paraplegia of lower legs after two consecutive lumbar punctures during two days. The lesion of spinal epidural hematoma was not found with lumbar spinal MRI but with cervico-thorasic one, because the lesion was at the C7-T6 level. Laminectomy was done to evacuate the hematoma and some specimen was obtained, of which pathologic finding was arteriovenous malformation. The boy is receiving physical therapy continuously due to unsatisfactory results with hematoma aspiration procedure and laminectomy treatment.