Stereotactic radiosurgery as the initial management option for small-volume hypothalamic hamartomas with intractable epilepsy: a 35-year institutional experience and systematic review.

OBJECTIVE: Young patients with hypothalamic hamartomas (HHs) often present with intractable epilepsy. Currently there are no established management guidelines for HH. The authors retrospectively reviewed their single-institution experience to delineate the role of stereotactic radiosurgery (SRS). METHODS: Seven patients with HHs (4 females; median age 13.7 years, range 2.5-25 years) with no prior resection underwent SRS between 1987 and 2022. The clinical history, epilepsy profile, radiographic findings, and neurological outcomes were characterized. HH topographical types were classified according to the Régis classification. Outcome measures included Engel seizure classification, HH response, and the need for additional surgical interventions. RESULTS: All patients had Engel class IV epilepsy. A Leksell Gamma Knife was used to deliver a median margin dose of 18 Gy (range 16-20 Gy) to a median hamartoma volume of 0.37 cm3 (range 0.20-0.89 cm3). Seizure reduction was confirmed in 6 patients, and 2 patients had regression of their hamartoma. Two patients underwent resection and/or laser interstitial thermal therapy after SRS. At follow-up, 1 patient was seizure free, 4 patients achieved Engel class II, 1 patient had Engel class III, and 1 patient had Engel class IV seizure outcomes. CONCLUSIONS: SRS as the initial management option for HH was associated with a low risk of adverse effects. In this institutional series reviewing small-volume HHs treated with SRS, no adverse radiation effect was detected, and the majority of patients experienced seizure reduction. SRS should be considered as the first-line treatment for seizure control in patients with small-volume HHs.

Safety and Efficacy of Primary Hypofractionated Gamma Knife Radiosurgery for Giant Hypothalamic Hamartoma.

OBJECTIVE: To describe the feasibility, safety, efficacy, and complication profile of primary hypofractionated gamma knife radiosurgery (GKRS), and practical nuances of performing the same in pediatric patients. METHODS: Three pediatric patients (age range 17-65 mo) underwent primary hypofractionated GKRS in 2-3 consecutive days with interfraction interval of 24 h. All patients had precocious puberty and were on GnRH analogue. Frame based GKRS done with 8.1-9.2 Gy radiation per fraction at 50% isodose in 2-3 fractions targeting the entire hamartoma volume. The mean target volume was 5.67 cc (4.45-7.39 cc). The authors followed these patients for clinical and endocrinological assessment at every 6 mo interval while the repeat MRI done at 6 mo and then annually. The seizure outcome analysis was done using Engel scale. RESULTS: At a mean follow up of 27 mo (24-30 mo), 2 patients became Engel class 3 while one achieved Engel class 1 control. 2 patients showed halted pubertal growth with no additional hormonal aberration. 2 patients showed significant volumetric reduction (48% and 32%) and patchy necrosis inside the hypothalamic hamartoma (HH). There was no deficit in visual function, memory and cognition. One patient showed reduction in aggressiveness. CONCLUSION: Giant HH are exceptionally difficult neurological diseases. Primary hypofractionated GKRS may be an alternative approach as mono/multitherapy with promising results and minimal complication.

Hypothalamic Hamartomas: A Comprehensive Review of Literature - Part 3: Updates on Radiotherapy Management.

Hypothalamic hamartomas (HH) are rare, non-neoplastic heterotopic tissues which contains normal neurons and glia including oligodendrocytes and fibrillary astrocytes but in an abnormal distribution. They arise from the floor of the third ventricle, tuber cinereum, or mammillary bodies. Estimated incidence ranges from 1 in 50,000 to 1 in 1,000,000. Hypothalamic hamartomas are associated with different clinical presentations including various types of seizures, most characteristically; the gelastic seizures, precocious puberty, cognitive impairment and behavioral changes. In this review, the authors discuss the recent advancements in different modalities of radiotherapy and their application in hypothalamic hamartomas management.

Risk-adapted, long-term management in childhood-onset craniopharyngioma.

PURPOSE: This report is a review of findings on the diagnosis, treatment, clinical course, follow-up, and prognosis of craniopharyngioma patients with special regard to clinical trials and long-term management. METHODS: Literature search on Pubmed for paper published after 1994. RESULTS: Craniopharyngiomas are rare, embryonic malformations of the sellar/parasellar region with low histological grade. Clinical manifestations are related to increased intracranial pressure, visual impairment, and hypothalamic/pituitary deficiencies. If the tumor is favorably localized, therapy of choice is complete resection, with care taken to preserve hypothalamic and optic functions. In patients with unfavorable tumor location (i.e. involvement of hypothalamic areas), recommended therapy is limited hypothalamus-sparing surgical strategy followed by irradiation. Irradiation has proven effective in treatment of recurrences and progression. Surgical lesions and/or anatomical involvement of posterior hypothalamic areas can result in serious sequelae, mainly hypothalamic syndrome. CONCLUSIONS: It is crucial that craniopharyngioma be managed as a frequently chronic disease, providing ongoing care of pediatric and adult patients' by experienced multidisciplinary teams in the context of multicenter trials.

The gelastic seizures-hypothalamic hamartoma syndrome: facts, hypotheses, and perspectives.

Hypothalamic hamartoma (HH) can be associated with a wide spectrum of epileptic conditions, ranging from a mild form with seizures characterized by urge to laugh and no cognitive involvement up to a catastrophic encephalopathy with early onset gelastic seizures (GS), precocious puberty, and mental retardation. Moreover, a refractory, either focal or generalized, epilepsy develops during the clinical course in nearly all the cases. Neurophysiologic and neuroimaging studies have demonstrated that HH itself generates GS and starts a process of secondary epileptogenesis responsible for refractory focal or generalized epilepsy. The intrinsic epileptogenicity of HH may be explained by the neurophysiological properties of small GABAergic, spontaneously firing HH neurons. Surgical ablation of HH can reverse epilepsy and encephalopathy. Gamma-knife radiosurgery and image-guided robotic radiosurgery seem to be useful and safe approaches for treatment, in particular of small HH. Here, we review this topic, based on literature reports and our personal observations. In addition, we discuss pathogenetic hypotheses and suggest new approaches to this intriguing issue.

Outcome and predictors of interstitial radiosurgery in the treatment of gelastic epilepsy.

BACKGROUND: Gelastic epilepsy due to hypothalamic hamartomas is usually a severe condition encompassing both epileptic seizures and an epileptic encephalopathy associated with behavioral and cognitive impairments. Here we report the effects of interstitial radiosurgery in the treatment of this generally pharmacoresistant epilepsy syndrome. METHODS: Twenty-four consecutive patients (3-46 years of age, 7 women, mean age 21.9 years, mean duration of epilepsy 17.6 years) with gelastic epilepsy due to MR-ascertained hypothalamic hamartoma and a minimum follow-up period of 1 year were included in this evaluation. Treatment was performed by interstitial radiosurgery using stereotactically implanted (125)I seeds. Effects of treatment on seizure frequency and possible side effects were assessed prospectively. Factors influencing outcome and side effects were analyzed statistically. RESULTS: After a mean 24-month follow-up period following the last radiosurgical treatment, 11/24 patients were seizure free or had seizure reduction of at least 90% (Engel class I and II), in some cases only after repeated treatment. The duration of epilepsy prior to radiosurgery negatively influenced outcome. Treatment was well tolerated in most patients. Headache, fatigue, and lethargy were transient side effects associated with the development of brain edema extending from the implantation site in five patients. Four patients had a weight gain of more than 5 kg which was severe in two patients. The majority of those patients whose cognitive functions initially deteriorated showed subsequent recovery of cognitive functions, but episodic memory in two patients showed persistent decline at 1 year follow-up. Longer disease duration increased the risk for cognitive side effects, and larger hamartoma size and eccentric seed positioning increased the risk for radiogenic brain edema. Neither perioperative mortality nor neurologic impairments, visual field defects, or endocrinologic disturbances were encountered following treatment. CONCLUSION: Interstitial radiosurgery was efficacious in significantly improving gelastic epilepsy in about half of the patients treated in this series. Weight gain may occur as a side effect, whereas other severe side effects reported following microsurgical removal of the hamartoma were absent. The study results strongly suggest early causal treatment, as chances for seizure control are higher and the risk for cognitive side effects is lower in patients with shorter disease duration.

Radiosurgery for hypothalamic hamartomas.

Radiosurgery plays an important role in the treatment of refractory seizures induced by hypothalamic hamartomas (HHs). These lesions, deeply located and surrounded by a delicate vascular and neuronal network, are often associated with catastrophic epilepsy leading to progressive cognitive and behavioral deterioration. Surgical approaches include microsurgical resection, endoscopic resection or disconnection, radiofrequency lesioning, and interstitial brachytherapy. Radiosurgery is an emerging treatment modality for HHs, which provides excellent seizure outcomes and no lasting complications to date.

Remission of refractory neurosarcoidosis treated with brain radiotherapy: a case report and a literature review.

Sarcoidosis is a chronic disease of unknown etiology characterized by the presence of T lymphocytes, mononuclear phagocytes, and noncaseating epithelioid granulomas in the tissues. Central nervous system involvement occurs in about 5% of the cases. The chronic form of neurosarcoidosis is particularly resistant to medical treatments. No universally accepted therapeutic protocols are currently available. Corticosteroids are the first line of therapy, but other immunosuppressive treatments are frequently added to the patient's regimen, although this strategy is not adequately supported by controlled clinical trials. For patients resistant to or not tolerating multiple alternate immunotherapeutic drugs, some authors suggest central nervous system radiotherapy. We present a case of a patient with neurosarcoidosis involving the hypothalamo-hypophyseal region and causing panhypopituitarism who had a poor response to and experienced severe side effects from conventional immunosuppressive treatments. The patient experienced a good clinical response to cranial irradiation. We review the literature on this subject.

Interstitial radiosurgery in the treatment of gelastic epilepsy due to hypothalamic hamartomas.

The authors evaluated a new stereotactic radiosurgical approach in seven patients with gelastic epilepsy due to hypothalamic hamartomas. Stereotactic implantation of 125I-seeds into the hamartoma was feasible in six patients. At follow-up at least 1 year after interstitial radiotherapy, two patients had become seizure-free within 2 months, and two others had only persisting auras. There were no major perioperative or postoperative side effects.

Langerhans cell histiocytosis limited to the pituitary-hypothalamic axis--two case reports.

Langerhans cell histiocytosis rarely presents as a solitary lesion in the pituitary-hypothalamic region, and is indistinguishable from germinoma, which occurs much more frequently, especially in Japanese. A 14-year-old girl and a 9-year-old girl presented with polydipsia and polyuria as the initial symptoms. Magnetic resonance (MR) imaging demonstrated a round mass at the pituitary stalk appearing as isointense on T1-weighted imaging and hyperintense on T2-weighted imaging. Endocrinological examination revealed mild hypopituitarism with central diabetes insipidus. Both patients underwent open craniotomy. Histological examination revealed granulomatous tissue with eosinophil infiltration and frequent Langerhans histiocyte clustering, compatible with the diagnosis of Langerhans cell histiocytosis. Low-dose local irradiation of 20 Gy was administered. First patient was followed up for 8 years, and her hypopituitarism gradually improved to a minimal level with only amenorrhea as the residual symptom. Recent MR imaging showed no residual mass at the region. Second patient was followed up for 15 months, and her diabetes insipidus is stable. MR imaging performed 5 months after the treatment showed marked reduction of the mass. These cases reemphasize the importance of histological diagnosis for lesions with similar neuroimaging appearances. Biopsy and low-dose irradiation are an effective treatment for this rare and essentially benign lesion, as opposed to attempting total removal of the mass.

Neurosarcoidosis presenting as hypopituitarism and a cystic pituitary mass.

We report a young woman with clinical hypopituitarism and systemic sarcoidosis involving the lung, gastrointestinal tract, and peripheral lymph nodes. Laboratory evaluation confirmed that cortisol, thyroid indices, insulin-like growth factor 1, follicle-stimulating hormone, luteinizing hormone, and estradiol levels were low, with a normal prolactin. Magnetic resonance imaging revealed a large cystic pituitary lesion compressing the optic chiasm and exhibiting rim but not hypothalamic enhancement. The differential diagnosis included cystic macroadenoma, Rathke's cleft cyst, craniopharyngioma, and simple cyst. A transsphenoidal procedure provided decompression and diagnosis: pathology was consistent with sarcoidosis. Postoperatively, the patient's neurosarcoid disease markedly worsened, requiring hypothalamic irradiation. To our knowledge, this is the first report of intracranial sarcoidosis presenting solely as a cystic pituitary mass. An awareness of this possibility is important to prevent inappropriate neurosurgical intervention and subsequent potential exacerbation of neurosarcoidosis.

Hypothalamic histiocytosis X with diabetes insipidus and Korsakoff's syndrome--case report.

A 54-year-old female presented with apparent isolated hypothalamic histiocytosis X associated with diabetes insipidus and Korsakoff's syndrome. Computed tomographic and magnetic resonance imaging demonstrated a single hypothalamic mass. A craniotomy for biopsy found granulation tissue of unknown cause. Further investigation discovered genital bleeding before admission. Biopsy of the cervix uteri revealed histiocytosis X. Further studies showed the disease was restricted to the hypothalamus and the endometrium of the cervix uteri. Low-dose irradiation led to partial regression of the hypothalamic mass and improvement of Korsakoff's syndrome. Even when a diagnosis of isolated hypothalamic histiocytosis X is confirmed, the possibility of another histiocytosis X lesion in an unexpected region must be considered.

Histiocytosis X of the hypothalamus.

An 18-year-old woman presented with visual disturbance and endocrine dysfunction (diabetes insipidus, delayed puberty, hypothyroidism, hypoadrenalism, and hyperprolactinemia). Computed tomography and enhanced cisternography showed a single hypothalamic mass, which proved at biopsy to be histiocytosis X. Further studies showed the disease to be restricted to the hypothalamus. The patient was treated with hormonal replacement therapy, but her visual acuity continued to worsen. Visual acuity improved after low-dose irradiation of the pituitary fossa and hypothalamus, which also led to disappearance of the mass. This case shows that localized hypothalamic histiocytosis X can be diagnosed and treated successfully before other systems become involved.

Plasma cell granuloma of the hypothalamic region.

Two patients suffering from diabetes insipidus, with additional symptoms of impaired vision and signs of panhypopituitarism and increased intracranial pressure, showed a normal sella tursica in the X-ray examination of the skull but large, dense space-occupying lesions in the hypothalamus on CT scans of the brain. NMR performed in one patient disclosed suprasellar growth of a hypothalamic lesion. Proliferation of lymphoplasmocytes and mature plasma cells was seen by light microscopic and electromicroscopical examination of biopsy samples in both cases; histiocytes and multinucleated giant cells were absent; tuberculosis, syphilis and sarcoidosis were ruled out by appropriate tests. Plasma cells exhibited polyclonal immunoglobulin expression as revealed by immunocytochemistry using the PAP method. Taken together these features are typical of plasma cell granuloma. Transitory remission after radiotherapy was obtained in one patient.