Hypothalamic Hamartoma Research Articles

Intraprocedural Three-Dimensional Imaging Registration Optimizes Magnetic Resonance Imaging–Guided Focused Ultrasound and Facilitates Novel Applications

BACKGROUND AND OBJECTIVE: Transcranial magnetic resonance–guided focused ultrasound (MRgFUS) has revolutionized ablative treatment of essential tremor in recent years. However, limitations in precision targeting may account for suboptimal efficacy and significant side effects. We describe a simple intraprocedural three-dimensional image-guided lesion shaping technique that can improve overall outcomes of MRgFUS for essential tremor and facilitate expansion to novel indications. METHODS: A retrospective review of 84 consecutive MRgFUS procedures performed at Pennsylvania Hospital was performed. Comparison of patient demographics, treatment parameters, and clinical outcomes before and after implementation of this protocol was conducted. Further application of this technique in pallidotomy treatments and ablative disconnection of hypothalamic hamartoma are described. RESULTS: After implementation, the median of total number of sonications (7 vs 9, P = .001), number of therapeutic sonications (3 vs 4, P < .0001), and interval time between the first and last sonication (46:10 vs 68:53 minutes, P = .0004) were significantly reduced. Patients expressed greater satisfaction of treatment (94.1% vs 82.4%, P = .018), greater global impression of change (CGI) (7 vs 6, P = .033), and reduced median number of side effects at 6 months (0 vs 1, P = .026). We also successfully implemented this protocol for novel indications. CONCLUSION: Intraprocedural lesion shaping for MRgFUS is a simple and versatile imaging protocol augmentation that improves ablation precision and can improve treatment efficacy and broader neurological application.

CSIG-05. IS THERE ANY BRAIN TUMOR PREDISPOSITION IN RELATED PALLISTER-HALL SYNDROMES AT THE NEW GENOMICS ERA

Abstract Pallister-Hall Syndrome (PHS) and its related syndromes are a spectrum of congenital malformations. They are associated to GLI3 mutations and specific brain tumors. Considered as lethal, it is now well established that this disease may be miss-diagnosed with the report of adult cases. Here, we discuss the management of the genetic counselling and the risk of neurologic tumor predisposition in GLI3-related PHS. We comprehensively reviewed the scientific literature using various databases to explore the risk of neurologic tumors and evolving practice of neuro-cancer genetic counseling in GLI3-related PHS. The review of literature showed that GLI3 is involved in tissue development as well as in cancer. GLI3 was identified as either a pro or anti-cancerous protein. In fact, GLI3 is described as upregulated in multiple cancers and is found to positively regulate malignant behavior. In neuro-oncology GLI gene was first identified as a highly expressed gene in human glioma and then as having an anti-cancerous role in medulloblastoma where GLI3 seems act as a tumor suppressor. In mutational studies, GLI3-germinal mutations are characterized by a high recurrence of hypothalamic hamartoma in syndromic patients. GLI3-somatic alterations have been also demonstrated in cell samples of patients with non-syndromic hypothalamic hamartoma. In addition, while inactivation of GLI3 is suggested to be associated with medulloblastoma, mutations are not common in sporadic medulloblastoma. The association of germinal GLI3 variants in syndromic patients with medulloblastoma has been identified in only one patient harboring GLI3 H302X variant. Our review permitted us to conclude that germline GLI3 mutations may predispose to a specific non-severe form of delayed hypothalamic hamartoma, which can be revealed in pauci or asymptomatic and unrecognized mutated individuals. The likelihood of having a neuro-cancer predisposition in GLI3 mutated families seems to be insignificant.

How I do it: MRI-guided stereotactic navigation for Laser Interstitial Thermal Therapy.

MR-guided stereotaxy has emerged as a viable alternative to CT-guided frame-based or frameless approaches. By offering direct MR-guided navigation, this technique addresses most limitations inherent to CT navigation, enabling submillimeter precision. We detail the workflow of using the ClearPoint® MR navigation system for laser catheter placement in the treatment of a hypothalamic hamartoma. MR-guided navigation is a precise and effective stereotactic method for laser ablation of targets with high demands for accuracy. However, compared to standard stereotactic techniques, MR-guided navigation is more time-consuming and costly.

Endoscopic Epilepsy Surgery: Systematic Review and Meta-Analysis

AbstractEndoscopic epilepsy surgery is a fast emerging minimally invasive alternative to open surgery. The approach minimizes the extent of bone and brain resection and reduces surgical morbidity. This systematic review and meta-analysis sought to evaluate the favorable outcome of seizure improvement in patients undergoing endoscopic epilepsy surgery. The search was conducted by two independent researchers using PubMed and Web of Science until January 2023 to find studies reporting results of patients who underwent endoscopic epilepsy surgery. We extracted data on the clinical profile and outcomes of the patients from the eligible studies. Fifteen studies yielded 340 patients, of which 293 underwent endoscopic epilepsy surgery. The patient cohort consisted of 189 (55.6%) males. A total of 171 (58.3) patients had a favorable outcome of either Engel I or II or > 90% seizure control. Thirteen studies were included in our meta-analysis, and demonstrated improved seizure control after endoscopic epilepsy surgery, with a pooled seizure freedom rate of 58% (95% CI: 0.43–0.71, I2 = 77.1%, τ2 = 0.6836). Studies focusing on pediatric populations reported a higher proportion of positive outcomes, with a rate of 73.27% (95% CI: 62–82%, I2 = 0.0%). In comparison, mixed-age populations showed a lower success rate of 48% (95% CI: 32–65%, I2 = 79.0%). Furthermore, there was significant difference in treatment outcomes between the pediatric and mixed age groups (p = 0.014). The hypothalamic hamartomas (HH) patient population demonstrated a favorable outcome proportion of 61.71% (95% CI: 48.92–73.06%), with a moderate level of heterogeneity (I 2 = 62.9%, tau2 = 0.4266). Five patients developed postoperative complications, and there were three deaths. Our findings suggest that endoscopic epilepsy surgery is particularly effective in pediatric populations and among patients with HH, underscoring the importance of considering patient demographics and disease characteristics in clinical decision-making. The heterogeneity across studies necessitates cautious interpretation of the pooled results, advocating for tailored approaches in treatment planning. Prospective trials are required to establish class I evidence for the role of endoscopic epilepsy surgery compared with the recognized open surgical techniques.

Ictal and interictal epileptic networks of 34 patients with Hypothalamic Hamartoma on scalp electroencephalography.

To investigate ictal and interictal cortical involvement in epilepsy associated with hypothalamic hamartoma. We conducted a retrospective study of 34 patients with epilepsy and hypothalamic hamartoma, using data from long-term video-EEG-monitoring. We analyzed onset and propagation of ictal and interictal scalp EEG and visualized the resulting networks of cortical involvement. According to clinical and EEG criteria we grouped patients in: (1) focal disease, (2) focal advanced disease, (3) extended disease. We compared networks between these groups and different seizure types. Eight patients underwent several video-EEGs, and we analyzed all to investigate epilepsy progression. Epileptic activity mainly involved frontal and temporal cortex regions. Involvement of frontal regions was more common in advanced stages of the disease, and strong fronto-temporal connections were observed in the ictal networks of patients in intermediate stages (25.0% (left) and 35.7% (right) of seizures with EEG correlate). Occurrence and timing of EEG-correlate significantly depended on the seizure type (Chi-2-test, p<<0.001). In patients with several EEGs, seizure activity increased by +0.67 seizures/day/month (mean). There were significant differences between patients with normal and impaired cognitive function, with the latter showing pronounced ictal involvement of fronto-temporal cortex areas (p<0.001). Overall, in epilepsy due to hypothalamic hamartoma, cortical involvement focuses on frontal and temporal regions and varies systematically with the stage of the disease, different seizure types and presence of impaired cognitive function. We propose that these data may help improve our general understanding of epileptogenesis and potentially provide insights for the surgical therapy of hypothalamic hamartomas.

7202 CPP with Rapid Pubertal Progression in a 9-Year-Old Boy with Hypothalamic Teratoma

Abstract Disclosure: R. Robilliard: None. G. Tung: None. K. Svokos: None. R. Lulla: None. J.Q. Quintos: None. Background: Central Precocious Puberty (CPP) in males is rare, with incidence of 0.01-2/10,000. The most common identifiable cause of CPP in young children is hypothalamic hamartoma. No case hypothalamic teratoma has been reported to cause CPP in males. Clinical Case: At the age of 10-years and 5-months, a boy presented to the pediatric endocrinology with signs of precocious puberty including facial hair development, voice deepening, and increased growth velocity that began at 9 years old. There was no significant past medical history and he denied headache, blurry vision, or diplopia. Physical examination showed height of 140.4 cm (47%), Tanner 4 genitalia, Tanner 3 pubic hair, and testicular volumes of 15 cc (left) and 12-15cc (right). Bone age (BA) determined by radiography was 13.5 years with a predicted adult height (PAH) of 63 inches. The mid-parental target height was 67 +/- 4 inches. Evaluation including TSH, glucose, serum and CSF β-HCG, DHEA, CSF AFP was normal. Serum LH was 2.9 IU/L and testosterone level was 109 ng/dl, consistent with CPP. MRI of the pituitary showed a small, heterogeneous and fat-containing lesion extending inferiorly from the tuber cinereum consistent with teratoma. Treatment included GnRH agonist Lupron (30mg) every 3 months. Laboratory evaluation 8 months after initial presentation showed suppressed LH of 0.9 IU/L and FSH 0.5 mIU/mL, and testosterone of 57 ng/dL. Repeat radiography for BA one year after GnRHa suppression showed BA of 14 years at CA of 11 years 6 months and PAH of 64.4 inches. Growth velocity slowed to 5.3 cm/year. At the most recent follow-up visit at CA of 12 years, height was 151.5 cm (61%), growth velocity 6.3 cm/year (74% for age), Tanner 5 penis and pubic hair, left testicular volume of 15-20cc and right testicular volume of 15 cc. Most recent radiographic BA is14 years, and PAH is 65.9 inches. Given response to GnRH agonist injections every 3 months, the absence of CNS symptoms referable to the teratoma and no change in MR imaging, no surgical intervention is recommended. Conclusion: This is the first case of a hypothalamic teratoma reported in a male associated with CPP. Despite this rare cause, the patient has responded to standard treatment with GnRH agonist therapy alone. Presentation: 6/1/2024

Genetic Insights Into Hypothalamic Hamartoma: Unraveling Somatic Variants.

Hypothalamic hamartomas (HHs) are rare developmental brain lesions associated with drug-resistant epilepsy and often subjected to epilepsy surgery. Brain somatic variants in genes affecting the Sonic hedgehog (Shh) and primary cilia signaling pathways have been implicated in approximately 50% of nonsyndromic HH cases. This study aims to characterize a new cohort of 9 HH cases and elucidate their genetic etiology. We recruited 9 HH cases including 8 nonsyndromic cases of which 4 were type IV HH. Genomic DNA was extracted from peripheral blood and surgical brain tissues, and somatic variants were investigated using high-depth whole-exome sequencing. Pathogenic somatic variants in known HH genes (GLI3, OFD1, and PRKACA) were identified in 7 of the 9 cases. In addition, a 2-hit mutational event comprising a germline variant (predicted to impair kinase activity) and a somatic loss-of-heterozygosity was identified in TNK2, a gene encoding a brain-expressed tyrosine kinase. Our findings reinforce the role of somatic variants in Shh and cilia genes in HH cases while also shedding light on TNK2 as a potential novel disease-causing gene. This study emphasizes the increasing importance of brain mosaicism in epilepsy disorders and underscores the critical role of genetic diagnosis derived from resected brain tissue.

MR-guided laser interstitial thermal therapy in the treatment of brain tumors and epilepsy.

MR-guided Laser Interstitial Thermal Therapy (MRgLITT) is a minimally invasive neurosurgical technique increasingly used for the treatment of drug-resistant epilepsy and brain tumors. Utilizing near-infrared light energy delivery guided by real-time MRI thermometry, MRgLITT enables precise ablation of targeted brain tissues, resulting in limited corridor-related morbidity and expedited postoperative recovery. Since receiving CE marking in 2018, the adoption of MRgLITT has expanded to more than 40 neurosurgical centers across Europe. In epilepsy treatment, MRgLITT can be applied to various types of focal lesional epilepsy, including mesial temporal lobe epilepsy, hypothalamic hamartoma, focal cortical dysplasias, periventricular heterotopias, cavernous malformations, dysembryoplastic neuroepithelial tumors (DNET), low-grade gliomas, tuberous sclerosis, and in disconnective surgeries. In neuro-oncology, MRgLITT is used for treating newly diagnosed and recurrent primary brain tumors, brain metastases, and radiation necrosis. This comprehensive review presents an overview of the current evidence and technical considerations for the use of MRgLITT in treating various pathologies associated with drug-resistant epilepsy and brain tumors.

Surgical and radiosurgical treatment of hypothalamic hamartoma: The Italian experience between 2011 and 2021.

To investigate the Italian experience on the surgical and radiosurgical treatment of drug-resistant epilepsy due to hypothalamic hamartoma (HH) in the period 2011-2021 in six Italian epilepsy surgery centers, and to compare safety and efficacy profiles of the different techniques. We collected pseudo-anonymized patient's data with at least 12 months of follow-up. Surgical outcome was defined according to Engel classification of seizure outcome. Univariate analysis was performed to assess the risk of post-operative seizures, categorized in dichotomous variable as favorable and unfavorable; explanatory variables were considered. Mann-Whitney or Chi-squared test were used to assess the presence of an association between variables (p < 0.05). Full presurgical and postoperative data about 42 patients from 6 epilepsy surgery centers were gathered. Engel class I was reached in the 65.8% and 66.6% of patients with gelastic and non-gelastic seizures, respectively. Other than daily non-gelastic seizures were associated with seizure freedom (p = 0.01), and the radiological type presented a trend toward significance (p = 0.12). Endoscopic disconnection and laser interstitial thermal therapy are effective in the treatment of HH-related epilepsy, with a tolerable safety profile. Both gelastic and non-gelastic seizures can be treated, also in patients with a long history of seizures. This study collected data about 42 patients with HH-related epilepsies. Endoscopic disconnection and laser therapy are both effective and safe in the treatment of hypothalamic hamartoma-related epilepsies.

Hamartomas of the Tuber Cinereum Associated with X-Linked Deafness Show Signs of Pubertas Tarda Instead of Pubertas Praecox and No Gelastic Seizures-Long-Term Follow-Up of 12 Years.

Hamartomas of tuber cinereum present as ectopic tissue in the hypothalamic region. Clinically, the usual hypothalamic hamartomas manifest themself by gelastic seizures and pubertas praecox. We observed an increased coincidence of the presence of X-linked recessive deafness DFNX2 (DFN3) and a hamartoma of the tuber cinereum. Initially five patients presented with hearing loss in childhood, two additional were already adults, not showing any characteristic symptoms for a hamartoma but signs of delayed puberty. Seven patients who underwent computed tomography imaging due to a sensorineural hearing loss and had a hamartoma of the tuber cinereum in addition to X-linked deafness DFNX2 (DFN3) were included in a retrospective study. Patients underwent initial neurologic, endocrinologic, and genetic evaluation. Long-term follow-up was performed after 10 to 12 years. The average age at the initial exam was 12.9 years (range 4-29). All patients genetically proven nonsyndromic, X-linked deafness associated with the POU3F4 gene. Three out of six patients presented signs of delayed puberty. None of all seven showed any evidence of pubertas praecox or gelastic seizures at mean age of 17 years (range 17-29 years) at any time. Hamartomas of tuber cinereum are often coincident with DFNX2. Clinically, half of the cases are-in contrary to the usual pubertas praecox-associated with growth hormone deficiency and delayed puberty, in the sense of pubertas tarda, when coincident. Clinicians' and radiologists' knowledge and awareness of this rare combination are crucial to identify children early enough for hormone-sensitive treatment.

Central Precocious Puberty in a 5-year-old Boy with Hypothalamic Hamartoma: A Case Report and Review of the Literature

Background: Central precocious puberty (CPP) occurs due to the precipitous production of gonadotropin-releasing hormone (GnRH) and premature activation of the hypothalamic-gonadal axis. It is the most typical endocrine symptom of hypothalamic hamartoma. Hypothalamic hamartomas (HH) are rare, non-cancerous malformations of the central nervous system (CNS). They can show up as CPP related to the release of luteinizing hormone in addition to developmental delay, visual impairments, hyperactivity, or gelastic seizures in young children. Case Description: In this study, we present the case of a five-year-old Afghan child who displayed quickly evolving secondary sexual traits linked to hypothalamic dysfunction. Endocrine testing supported the central underlying cause of early puberty. The early detection of a small-sized, rounded lesion at the base of the tuber-cinereum on Magnetic Resonance Imaging (MRI) led to the diagnosis of Hypothalamic hamartoma (HH). To delay puberty, the patient was treated conservatively with a long-acting gonadotropin-releasing hormone (GnRH) analogue and his response was monitored. Conclusion: This case report includes a review of the relevant literature as well as possible management strategies for a hypothalamic hamartoma.

Stereotactic Radiosurgery in the Management of Intractable Seizure Due to Hypothalamic Hamartoma

Stereotactic Radiosurgery in the Management of Intractable Seizure Due to Hypothalamic Hamartoma

Gamma Knife Radiosurgery for Hypothalamic Hamartoma: A Multi-Institutional Retrospective Study on Safety, Efficacy, and Complication Profile.

Gamma knife radiosurgery (GKRS) is a safe and effective treatment option for hypothalamic hamartomas (HH), but there is no consensus opinion on its timing, dosage, and follow-up. The aim of this study was to define the safety, efficacy, outcome, and complication profile of GKRS in this patient population. This retrospective multicentric study involved 39 patients with the mean age of 16 ± 14.84 years. Early seizures resulted in an earlier age of diagnosis in 97% of patients. At baseline, no endocrine abnormalities were seen in 75% of patients while 18.9% showed precocious puberty (PP). The median target volume was 0.55 cc (0.1-10.00 cc), and a median margin dose of 16 Gy (8.1-20.0 Gy) was delivered in a single session. All patients were evaluated for clinical, endocrinological, and radiological outcomes. The median follow-up was 5 (0.1-15) years. The median target volume of the cohort was 0.55 (0.35-1.77) cc. The largest HH was of 10 cc. 24/39 (61.5%) were small HH (Regis I-III). At presentation, 94.8% patients suffered from seizures (87.18% with gelastic seizures). 7/39 patients (17.9%) were presented with both PP and epilepsy. Only one (2.6%) patient presented with PP alone. 29 patients had more than 3-year follow-up. All received ≥16 Gy targeting complete HH. 28% of patients showed regression in HH volume. Patients with Regis grade I-III and longer follow-up (>75 months) showed gradual improvement in seizures. 16/29 patients (55.2%) achieved good seizure control (Engel I/II) while 13 (44.8%) were in Engel III/IV status. Nine patients needed adjuvant treatment because of poor seizure control. Eight patients suffered from transient increase in seizures. One patient developed poikilothermia, and 2 patients developed new onset hormonal deficiency. GKRS is a safe and effective modality for treatment of HH with significant improvement in seizure control with minimal disruption of endocrine profile. It provides an excellent safety, efficacy, and complication profile, especially for small HH. Latency of results and its adjuvant nature remain the areas of research and breakthroughs among contemporary treatment options.

Robot-assisted laser interstitial thermal therapy for drug-resistant epilepsy in hypothalamic hamartoma.

Hypothalamic hamartomas are congenital lesions of the hypothalamus, with a range of symptoms defined by lesion location. Common presenting symptoms include gelastic seizures and precocious puberty. When hamartoma-related seizures become resistant to medications, laser interstitial thermal therapy (LITT) has been shown to be an effective treatment. The authors present a case of robot-assisted LITT for a patient with an 11-year history of epilepsy due to hypothalamic hamartoma. In addition, they demonstrate the use of a stereotactic biopsy needle implemented during the procedure for possible biopsy of deep cranial lesions. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2415.

Hypothalamic Hamartoma in an 11-Year-Old Female: Clinical Presentation, Diagnostic Evaluation, and Management Strategies – A Case Report and Literature Review

Background: Hypothalamic hamartomas (HH) are rare, benign brain tumors that can cause severe neurological symptoms, including epilepsy. This report presents a case of an 11-year-old female with HH, highlighting the clinical presentation, diagnostic workup, and management strategies. Case Presentation: An 11-year-old female with no prior medical history presented with generalized tonic-clonic seizures during sleep, characterized by convulsions, cyanosis, tongue biting, frothing at the mouth, and loss of consciousness lasting 1-2 minutes. Subsequent episodes included focal Jacksonian seizures involving the face and right eye myoclonus, progressing to generalized convulsions. Neurological examination and development were normal, with no family history of epilepsy. MRI revealed a sessile lesion in the left hypothalamus with T2/FLAIR hyperintensity and T1 hypointensity. Laboratory tests, including thyroid function, gynecological ultrasound, and various blood tests, were normal. A 48-hour video EEG indicated sensorimotor cortex involvement in both hemispheres, likely linked to the hypothalamic lesion. Management: Initial management involved observation without antiepileptic medications. Due to persistent seizures, the treatment plan included oxcarbazepine, titrated to 1200 mg/day, and Keppra (levetiracetam) 1000 mg/day. Efforts were made to discontinue Keppra and maintain monotherapy with oxcarbazepine. Given the small size of the lesion and effective seizure control with medication, surgical intervention was not pursued. Conclusion: This case underscores the importance of comprehensive diagnostic evaluation and individualized treatment plans for patients with HH. While medical management can be effective for small lesions, surgical options reported in the literature provide alternative strategies for larger or treatment-resistant cases. A multidisciplinary approach is crucial in managing the complex presentation of HH to optimize patient outcomes and improve quality of life.

Cognitive Dysfunction due to Gelastic Seizures with Hypothalamic Hamartoma

Cognitive Dysfunction due to Gelastic Seizures with Hypothalamic Hamartoma

Direct resection is a safe and effective strategy to control seizures in patients with hypothalamic hamartoma

Achieving favorable seizure outcomes is challenging in patients with seizures resulting from hypothalamic hamartoma. Although minimally invasive and non-invasive surgical procedures are used to treat this population, these procedures have limitations. Therefore, we analyzed the outcomes of patients with hypothalamic hamartoma following direct resection. We included 159 patients with hypothalamic hamartoma who underwent direct resection using the transcallosal interforniceal approach between 2011 and 2018. The relationships between clinical parameters and seizure outcomes were analyzed. In total, 55.3% achieved gross total resection and 25.2% underwent near-total resection. Of all patients, 79.2% were overall seizure-free at one year, but this number dropped to 77.0% at more than five years. Moreover, 88.4% (129/146) reached gelastic seizure (GS)-free status at one year and this number increased to 89.0% (97/109) at more than five years. Seventy-one patients took antiseizure medication (ASM) long-term, 68 took it for one year, and 11 took it for one-half year. The duration of ASM consumption (p < 0.001) and extent of hypothalamic hamartoma resection (p = 0.016) were significant independent predictors of long-term overall seizure-free survival, while the duration of ASM consumption (p = 0.011) and extent of hypothalamic hamartoma resection (p = 0.026) were significant independent predictors of long-term GS-free survival. Most patients' behavior, school performance, and intelligence were not affected after surgery. Direct resection is effective and safe strategy for patients with hypothalamic hamartomas. Hypothalamic hamartomas should be removed as completely as possible, and patients should take ASM long-term following surgery to reach long-term overall seizure-free or GS-free status.

Epileptic encephalopathies secondary to hypothalamic hamartomas treated with radiosurgery: A case series.

Hypothalamic hamartomas are congenital lesions that typically present with gelastic seizures, refractory epilepsy, neurodevelopmental delay, and severe cognitive impairment. Surgical procedures have been reported to be effective in removing the hamartomas, however, they are associated with significant morbidity. Therefore, it is not considered a safe therapeutic modality. Image-guided robotic radiosurgery (CyberKnife® Radiosurgery System) has been shown to provide good outcomes without lasting complications. This series of cases describes the clinical, radiological, radiotherapeutic, and postsurgical outcomes of five patients with epileptic encephalopathies secondary to hypothalamic hamartomas who were treated with CyberKnife®. All patients exhibited refractory epilepsy with gelastic seizures and were unsuitable candidates for surgical resection The prescribed dose ranged between 16 and 25 Gy, delivered in a single fraction for four patients and five fractions for one patient while adhering strictly to visual pathway constraints. After radiosurgery, four patients maintained seizure control (one with an Engel class Ia, three with an Engel class 1d), and another presented sporadic, nondisabling gelastic seizures (with an Engel class IIa). After 24-26 months of follow-up, in three patients, their intelligence quotient scores increased. No complications were reported. This report suggests that Cyberknife may be a good option for treating hypothalamic hamartoma, particularly in cases where other noninvasive alternatives are unavailable. Nevertheless, additional studies are essential in order to evaluate the effectiveness of the technique in these cases.

Population-based study of rare epilepsy incidence in a US urban population.

This study was undertaken to estimate incidence of rare epilepsies and compare with literature. We used electronic health record text search to identify children with 28 rare epilepsies in New York City (2010-2014). We estimated cumulative incidence and compared with literature. Eight of 28 rare epilepsies had five or more prior estimates, and our measurements were within the published range for all. The most common were infantile epileptic spasms syndrome (1 in 2920 live births), Lennox-Gastaut syndrome (1 in 9690), and seizures associated with tuberous sclerosis complex (1 in 14 300). Fifteen of 28 had fewer than five prior estimates, and of these, we provided additional estimates for early infantile developmental and epileptic encephalopathy (1 in 32 700), epilepsy with myoclonic-atonic seizures (1 in 34 100), Sturge-Weber syndrome plus seizures/epilepsy (1 in 40 900), epilepsy in infancy with migrating focal seizures (1 in 54 500), Aicardi syndrome plus seizures/epilepsy (1 in 71 600), hypothalamic hamartoma with seizures (1 in 225 000), and Rasmussen syndrome (1 in 450 000). Five of 28 rare epilepsies had no prior estimates, and of these, we provided a new estimate for developmental/epileptic encephalopathy with spike-and-wave activation in sleep and/or continuous spikes and waves during sleep (1 in 34 100). Data were limited for the remaining 12 rare epilepsies, which were all genetic epilepsies, including PCDH19, CDKL5, Alpers disease, SCN8A, KCNQ2, SCN2A, GLUT1 deficiency, Phelan-McDermid syndrome, myoclonic epilepsy with ragged-red fibers, dup15q syndrome, ring chromosome 14, and ring chromosome 20. We estimated the incidence of rare epilepsies using population-based electronic health record data and literature review. More research is needed to better estimate the incidence of genetic epilepsies with nonspecific clinical features. Electronic health records may be a valuable data source for studying rare epilepsies and other rare diseases, particularly as genetic testing becomes more widely adopted.

An Unusual Case of Hypothalamic Hamartoma With Nongelastic Seizures and Posterior Cortex Connectivity

BackgroundTo describe a rare seizure semiology originating from a hypothalamic hamartoma in a child, along with unusual ictal onset and connectivity pattern, and provide a review of the pathophysiology of epilepsy associated with hypothalamic hamartoma and management. MethodsA detailed retrospective chart review and literature search were performed using Pubmed and Embase. ResultsWe present a case of a three-year-old male who presented with dyscognitive seizures with onset at age 22 months. Stereoelectroencephalography exploration confirmed the onset in hypothalamic hamartoma with rapid propagation to the temporal-parietal-occipital association cortex and precuneus. The patient's epilepsy was cured with laser ablation of the hamartoma. ConclusionPublished literature mostly describes a more anterior frontal or temporal epileptic network with primarily gelastic seizures being the hallmark type of seizures associated with hypothalamic hamartoma. We highlight a rare posterior cortex network with an atypical presentation of focal nonmotor seizures with impaired awareness in the setting of a hypothalamic hamartoma. Stereotactic laser ablation of the hamartoma rendered seizure freedom. Early diagnosis and appropriate treatment can lead to seizure freedom.