Robotic-guided radiofrequency ablative disconnection of hypothalamic hamartoma.

Hypothalamic hamartomas (HHs) are benign masses, often associated with drug-refractory epilepsy (DRE). Open surgery as well as the endoscopic disconnection techniques are fraught with a high risk of morbidity and failure rates. The authors have been performing robotic-guided radiofrequency (RF) ablation for all types of HH presenting with DRE as a standard procedure at their institution. The authors have operated on 25 patients with HH using this technique over the last 8 years. This is a safe, effective, and minimally invasive technique. In this video article, the authors intend to demonstrate their technique of RF ablative disconnection under robotic guidance.

Multimodal Approach for the Treatment of Complex Hypothalamic Hamartomas.

Hypothalamic hamartomas (HHs) are rare congenital lesions formed by heterotopic neuronal and glial cells attached to the mammillary bodies, tuber cinereum, and hypothalamus.They often present with an intractable epilepsy typically characterized by gelastic seizures but commonly associated with other types of refractory seizures. The clinical course is progressive in most of the cases, starting with gelastic seizures in infancy and deteriorating into complex seizure disorders that result in catastrophic epilepsy associated with cognitive decline and behavioral disturbances.Hamartomas are known to be intrinsically epileptogenic and the site of origin for the gelastic seizures. As antiepileptic drugs are typically ineffective in controlling HH-related epilepsy, different surgical options have been proposed as a treatment to achieve seizure control. Resection or complete disconnection of the hamartoma from the mammillothalamic tract has proved to achieve a long-lasting control of the epileptic syndrome.Usually, symptoms and their severity are typically related to the size, localization, and type of attachment. Precocious puberty appears mostly in the pedunculated type, while epileptic syndrome and behavioral decline are frequently related to the sessile type. For this reason, different classifications of HHs have been developed based on their size, extension, and type of attachment to the hypothalamus.The bigger and more complex hypothalamic hamartomas typically present with severe refractory epilepsy, behavioral disturbances, and progressive cognitive decline posing a formidable challenge for the control of these symptoms.We present here our experience with the multimodal treatment for complex hypothalamic hamartomas. After an in-depth review of the literature, we systematize our approach for the different types of hypothalamic hamartomas.

Comprehensive review of status gelasticus: Diagnostic challenges and therapeutic insights.

Status gelasticus is a rare form of status epilepticus characterized by prolonged and/or clustered gelastic seizures. The review encompasses an analysis of cases reported in the literature, focusing on causes, clinical-electroencephalographic features, and therapeutic interventions. The study reveals the challenges in defining and understanding status gelasticus due to its diverse etiologies and limited reported cases. The association with hypothalamic hamartomas and other brain abnormalities underscores the importance of thorough evaluations. The review also discusses new treatments, including medications and less invasive surgeries. While progress has been made, the study points out challenges in diagnosing and managing this complex condition, highlighting the importance of ongoing research.

[Hypothalamic hamartoma dissection using focused ultrasound under MRI control. The first successful experience in Russia]. / Pervyi uspeshnyi opyt dissektsii gamartomy gipotalamusa metodom fokusirovannogo ul'trazvuka pod kontrolem MRT v Rossii.

Treatment of motor disorders by MRI-guided focused ultrasound is an alternative to neuro- and radiosurgery such as stereotactic radiofrequency ablation and thalamotomy with a gamma knife. However, safety, efficacy and feasibility of this technology for intracranial neoplasms are still unclear. The authors report successful hypothalamic hamartoma dissection by MRI-guided focused ultrasound in a 32-year-old woman with drug-resistant gelastic epilepsy and violent laughter and crying attacks. Magnetic resonance imaging revealed type II hypothalamic hamartoma. The last one was detached from surrounding brain tissue by MRI-guided focused ultrasound without side effects. Symptoms regressed immediately after surgery. No laughter and crying attacks were observed throughout 6-month follow-up.

Advances in hypothalamic hamartoma research over the past 30 years (1992-2021): a bibliometric analysis.

Background: Hypothalamic hamartoma (HH) is a rare intracranial disease whose manifestations include gelastic seizures and precocious puberty. The diagnosis and treatment of HH have changed substantially over the past three decades as medical care has improved. Bibliometrics can reveal the evolution and development of a scientific field. Methods: Documents on HH were retrieved from the Web of Science Core Collection (WoSCC) database on September 8, 2022. The search terms were as follows: "hypothalamic hamartoma" or "hamartoma of the hypothalamus" or "hypothalamic hamartomas." The types of documents were restricted to articles, case reports, and reviews. VOSviewer, CiteSpace, and the R package "bibliometrix" were used for a bibliometric analysis. Results: A total of 667 independent documents on HH were obtained from the WoSCC database. The most common types of documents were articles (n = 498, 75%) and reviews (n = 103, 15%). The number of annual publications fluctuated but showed an upward trend overall, and the annual growth rate was 6.85%. The cumulative publication data indicated that the most influential journals in the HH field include Epilepsia, Epileptic Disorders, Child's Nervous System, Neurosurgery, and the Journal of Neurosurgery. Kerrigan JF, Ng YT, Rekate HL, Regis J, and Kameyama S were among the most prominent authors in the field of HH, with numerous publications and citations. American research institutions, especially the Barrow Neurological Institute, occupied a pivotal position in HH research. Other countries and institutions were catching up and producing considerable research results. Research on HH has steadily switched its emphasis from Pallister-Hall syndrome (PHS) and precocious puberty to epilepsy and new diagnostic and therapeutic techniques, including Gamma Knife, laser ablation, and interstitial thermal therapy. Conclusion: HH remains a special neurological disease with significant research prospects. The development of novel technologies, including MRI-guided laser-induced thermal therapy (MRg-LiTT) and stereotactic radiofrequency thermocoagulation (RF-TC), has enabled the efficient treatment of gelastic seizures in HH while minimizing the risks associated with craniotomies. Through bibliometric analysis, this study points out the direction for future HH research.

Laughter isn't always the best medicine, sometimes it's one of the symptoms.

Gelastic seizure is a rare type of seizure characterized by bouts of uncontrolled, stereotyped laughter and often associated with hypothalamic hamartomas. In this case study we review a patient with a low grade ganglioglioma in the temporal lobe, a rare type of brain tumor that commonly causes seizures. The 8-year-old ambidextrous patient presented with seizures starting four days prior to presentation, happening multiple times daily and with each seizure lasting for 5-15 s. The patient's neurological examination was normal between episodes, and VEEG recorded ictal laughing events originating focally from the anterior temporal and/or inferior frontal region. Seizures were stopped with Levetiracetam, however given MRI findings surgical intervention was additionally deemed necessary. MRI head with contrast showed 8 mm nodular enhancing lesion located in the anteroventral portion of the right temporal pole with surrounding edema that extended to the anterior margin of the fusiform gyrus. The patient recovered well from surgery with no neurological deficits, is no longer on any antiseizure medications and remains seizure free at 3-year follow-up.

Ictal semiology of gelastic seizures.

Gelastic seizures are rare epileptic manifestations characterized by laughter or a smile. The main etiology is represented by hypothalamic hamartoma, but also focal localization of the epileptogenic zone is described. We reviewed a group of patients with gelastic seizures to describe the semiology and to establish any difference related to diverse epilepsy etiologies. Thirty-five seizures from 16 patients (6 females) were reviewed. The study confirms that hypothalamic hamartoma is the more frequent etiology associated with gelastic seizures. Laughter represented the majority of gelastic ictal signs, while the ictal smile was less frequent. In 87.5% of patients, the manifestation of laughter or smile was the only ictal phenomenon, or the first and the most important clinical sign. Interestingly, it has been observed that patients with a lesion localized in the hypothalamic region had more frequently laughter with emotional involvement and that laughter was the only manifestation of the seizure. On the contrary, patients with lesions localized outside the hypothalamic region had more often seizures with laugh without emotional involvement, resembling a more mechanical action, and associated with other semeiological signs. It, therefore, seems possible to assume that the emotional involvement and the expression of mirth during the seizure, especially in children, are more frequently associated with hypothalamic hamartoma. On the contrary, when the semiology includes less conveyed emotion similar to a mechanical action and other symptoms, an extra hypothalamic localization should be considered.

Magnetic Resonance-Guided Laser Interstitial Thermal Therapy for Hypothalamic Hamartoma: Surgical Approach and Treatment Outcomes.

Hypothalamic hamartoma (HH) is a rare lesion consisting of normal neurons and neuroglia arranged in an abnormal pattern which usually causes gelastic seizures (GS). Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has been developed as a minimally invasive approach to treat HH and gradually become a first-line treatment. In total, this study enrolled 47 consecutive HH patients that underwent one round of ablation. Patients were followed for at least one year. Patients' medical records and surgical information were carefully reviewed, and univariate analyses were performed. Of the treated patients, 72.3% remained GS-free in this study, with an overall Engel class I rate of 68.1%. Long-term postoperative complications occurred in six patients. Factors associated with GS prognosis included Delalande classification (p = 0.033), HH volume (p = 0.01), and the ablation rate of the HH body (p = 0.035). The disconnection rate was 0.73 ± 0.14 in the Engel class Ia group as compared to 0.62 ± 0.13 in the Engel Ib-Engel IV group (p = 0.046). MRgLITT represents a safe and effective surgical procedure. Patients with larger or Delalande type IV HH may require multiple rounds of ablation. In addition to assessing the degree of disconnection, ablation volume should also be carefully considered for patients undergoing this procedure.

Image-guided LINAC radiosurgery in hypothalamic hamartomas.

Introduction: Hypothalamic hamartomas (HH) are developmental malformations that are associated with mild to severe drug-refractory epilepsy. Stereotactic radiosurgery (SRS) is an emerging non-invasive option for the treatment of small and medium-sized HH, providing good seizure outcomes without neurological complications. Here, we report our experience treating HH with frameless LINAC SRS. Materials and methods: We retrospectively collected clinical and neuroradiological data of ten subjects with HH-related epilepsy that underwent frameless image-guided SRS. Results: All patients underwent single-fraction SRS using a mean prescribed dose of 16.27 Gy (range 16-18 Gy). The median prescription isodose was 79% (range 65-81 Gy). The mean target volume was 0.64 cc (range 0.26-1.16 cc). Eight patients experienced complete or near complete seizure freedom (Engel class I and II). Five patients achieved complete seizure control within 4 to 18 months after the treatment. Four patients achieved Engel class II outcome, with stable results. One patient had a reduction of seizure burden superior to 50% (Engel class III). One patient had no benefit at all (Engel class IV) and refused further treatments. Overall, at the last follow-up, three patients experience class I, five class II, one class III and one class IV outcome. No neurological complications were reported. Conclusions: Frameless LINAC SRS provides good seizure and long-term neuropsychosocial outcome, without the risks of neurological complications inherently associated with microsurgical resection.

MR imaging of hypothalamic hamartoma in a patient with gelastic seizures.

Hypothalamic hamartomas (HHs) are non-neoplastic malformations that occur in the region of the hypothalamus. HH is the leading cause of gelastic seizures in children and adolescents, where laughing is characteristically manifested. However, these patients can also experience different forms of complex or generalized tonic-clonic seizures that can obscure the diagnosis of HHs. We present a case of a 10 year-old boy that experienced several seizure types, but was subsequently diagnosed with HH after MR imaging was performed. This case highlights the complementary role of MR imaging in ascertaining seizure etiololgy when the clinical history and EEG findings are non-specific. The importance of early diagnosis with MR imaging is further underscored by the fact that patients diagnosed with HH usually develop drug resistance towards antiepileptic drugs, mandating neurosurgical assessment and intervention.

Gelastic seizures and the hypothalamic hamartoma syndrome: Epileptogenesis beyond the lesion?

The clinicoradiologic syndrome of hypothalamic hamartoma (HH) manifests with a variety of symptoms, including pharmacoresistant epilepsy with multiple seizure types, precocious puberty, behavioral disturbances, and cognitive impairment. Gelastic seizures are an early marker of epilepsy with HH in most of the cases. Despite a high variability, two major epilepsy phenotypes can be distinguished, based on electroclinical features: (i) focal seizures with epigastric or déjà-vu aura, loss of consciousness, and oroalimentary or gestural automatisms suggestive of temporal lobe involvement; and (ii) motor seizures with tonic, atonic, myoclonic, or versive phenomena, suggesting frontoparietal network involvement, with possible evolution toward an epileptic encephalopathy. The underlying physiopathologic mechanisms are not completely elucidated. The well-known intrinsic epileptogenicity of the HH represents the rationale for direct HH-aiming surgical procedures, with variable success in achieving seizure freedom. The concept of kindling-like secondary epileptogenesis has been suggested as a possible putative mechanism since the very beginnings of the hamartocentric era. Accordingly, a cortical area with enhanced epileptogenic properties due to an independent stage of secondary epileptogenesis would be responsible for seizures persisting after hamartoma ablation. However, recent intracerebral stereotactic EEG (SEEG) explorations demonstrated more complex, both reciprocal and hierarchical, relationships within the hypothalamo-cortical epileptogenic networks. Network formation may be due to either secondary epileptogenesis or widespread epileptogenicity present at the outset. A short time window from epilepsy onset to surgery seems to be crucial to cure epilepsy by direct surgery addressing a hamartoma. SEEG exploration may be reasonably proposed in cases where clinical data suggest an extension of the epileptogenic zone outside the limits of the HH, especially in focal seizures with impaired awareness and absence of gelastic seizures, or after a failure of the direct HH-aiming procedure.

MRI-Negative Occipital Lobe Epilepsy Presenting as Gelastic Seizures.

Although gelastic seizures (GSs) with extrahypothalamic epileptogenic zones such as the frontal, temporal, or parietal lobes have been previously reported, reports of GSs arising from the occipital region are rare. Herein, we describe the seizure propagation pattern of mirthless GSs confirmed by intracranial EEG in a case of MRI-negative occipital lobe epilepsy. In this patient, EEG onset was localized to the right occipital lobe while the onset of laughter coincided with seizure propagation to the right basal temporal region. This finding suggested that the symptomatogenic area for GSs in the occipital lobe may reside in the basal temporal region, and the basal temporal region may play a role in laughing behaviors. This case demonstrated that an elaborate analysis of electroclinical features combined with imaging findings may lead to successful seizure localization.

Ecstatic and gelastic seizures related to the hypothalamus.

Ecstatic seizures constitute a rare form of epilepsy, and the semiology is diverse. Previously, brain areas including the temporal lobe and the insula have been identified to be involved in clinical expression. The aim of this report is to review changes in ecstatic seizures in a patient before and after operation for a hypothalamic hamartoma, and to scrutinize the relation to gelastic seizures. In this case, the ecstatic seizures disappeared after surgery of the hamartoma but reappeared eleven years later. Clinical information was retrospectively obtained from medical records, interviews, and a questionnaire covering seizure semiology that pertained to ecstatic and gelastic seizures. Our findings imply a possible connection between gelastic and ecstatic seizures, originating from a hypothalamic hamartoma. To our knowledge, this location has not previously been described in ecstatic seizures. Gelastic seizures may in this case be associated with ecstatic seizures. We speculate that patients with ecstatic seizures may have an ictal activation of neuronal networks that involve the insula. Our case may add information to the knowledge concerning ecstatic seizures.

Hypothalamic hamartomas: A comprehensive review of the literature - Part 1: Neurobiological features, clinical presentations and advancements in diagnostic tools.

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 50,000-1 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 advancements in different diagnostic elements of hypothalamic hamartoma; including clinical features, EEG findings, and neuroimaging techniques. Moreover, different classifications described in the literature will be discussed.

Hypothalamic Hamartoma and Endocrinopathy: A Neurosurgeon's Perspective.

BACKGROUND: The management of hypothalamic hamartomas (HH) rests upon the type of presentation. These are rare congenital benign lesions presenting either with central precocious puberty (CPP), drug refractory epilepsy (DRE) or combination of both. We present here our experience in the management of these lesions from a neurosurgeon's perspective and review the pertinent literature. OBJECTIVE: To present a series of HH presenting with CPP and DRE managed in the neurosurgery department at our center with an emphasis on the associated endocrine abnormalities. MATERIALS AND METHODS: A prospective observational study over a period of five years included 16 patients of HH. All patients were evaluated with 3 Tesla Magnetic Resonance Imaging (MRI) brain, complete hormonal workup including gonadotrophins, testosterone (males) and estradiol (females), and video-electroencephalography (VEEG) as a part of epilepsy workup. All these patients were evaluated with postoperative hormonal workup and repeat MRI brain if repeat surgery was contemplated. RESULTS: Among the 16 patients of HH, there were 11 male and 6 female children. All the patients presented with DRE with four of these had associated CPP. All the patients underwent robotic-guided radiofrequency ablation (RFA), with 75% seizure freedom following 1st RFA surgery. Three of the four patients with CPP achieved both clinical and biochemical normalization. One patient had just a marginal reduction in the serum gonadotrophins. One patient was reoperated twice and three underwent RFA thrice. CONCLUSION: The management of HH should be individualized with DRE taking the precedence requiring early surgery. A multidisciplinary approach is therefore recommended for a successful outcome.

Ecstatic and gelastic seizures relate to the hypothalamus.

Ecstatic seizures constitute a rare form of epilepsy, and the semiology is diverse. Previously, brain areas including the temporal lobe and the insula have been identified to be involved in clinical expression. The aim of this report is to review changes in ecstatic seizures in a patient before and after operation of a hypothalamic hamartoma, and to scrutinize the relation to gelastic seizures. In this case, the ecstatic seizures disappeared after surgery of the hamartoma but reappeared eleven years later. Clinical information was retrospectively obtained from medical records, interviews, and a questionnaire covering seizure semiology that pertained to ecstatic and gelastic seizures. Our findings imply a possible connection between gelastic and ecstatic seizures, originating from a hypothalamic hamartoma. To our knowledge, this location has not previously been described in ecstatic seizures. Gelastic seizures may in this case were associated with ecstatic seizures. We speclate patients with ecstatic seizures may have an ictal activation of neuronal networks that involves the insula. Our case may add information to the growing knowledge concerning ecstatic seizures.

Gelastic seizures: a retrospective study in five tertiary hospital centres.

This study aimed to characterize, clinically and neurophysiologically, a series of patients with gelastic seizures (GS), including both adults and children. We retrospectively collected patients with GS from epilepsy clinics of five tertiary hospital centres within a single country. Patients were selected through relatives'/caregivers' descriptions, home video and/or video-EEG monitoring. GS were identified through ictal semiology. Thirty-five patients were enrolled; 62.9% had initial GS in infancy, 14.3% in adolescence and 22.8% at adult age. Twenty-six had abnormal MRI: eight presented with hypothalamic hamartoma (HH) and 16 non-HH lesions that included different structural aetiologies and genetic, metabolic and immune aetiologies. All patients with HH had their first GS in infancy or adolescence. For the remaining aetiologies, GS started in infancy in 59.3%, in adolescence in 11.1% and at adult age in 29.6%. Video-EEG data was available for analysis in 11 patients, including seven patients with a non-HH MRI lesion. The ictal onset topography on scalp video-EEG was usually concordant with the MRI lesion (in 6/7 patients) and the most frequent ictal onset was fronto-temporal. In two patients, both video-EEG and MRI suggested a parietal and occipital epileptogenic zone. Aetiologies and patterns of affected topography unrelated to HH are common in patients with GS, and all age groups may manifest with this type of ictal semiology. This ictal manifestation has no lateralizing value and, despite a clear preponderance for hypothalamic, frontal and temporal lobe origins, other brain areas, namely the parietal and occipital lobes, should be considered.