A meta-analysis of case-reports and case-series of dacrystic epilepsy in children and adolescence

This meta-analysis aimed to advance our knowledge about dacrystic epilepsy in children in the present time. PubMed searches for peer-reviewed case reports and case series were conducted using the keywords “dacrystic epilepsy”, “dacrystic seizures”, “crying epilepsy”, “ictal crying”, “crying seizures”. The databases were developed in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The author collected relevant information to characterise the study population including clinical outcome. Eleven studies out of 353 citations between 1998 and 26 May 2021 met the inclusion criteria, including both single cases and series pertaining to dacrystic epilepsy. Eight case reports and three case series were eligible for this meta-analysis and included twenty one cases. The seizure patterns were dacrystic seizures alone in seven cases (33%), and a combination of dacrystic seizures and gelastic seizures in fourteen cases (67%). Neuroimaging revealed structural abnormality in 95% cases. Hypothalamic hamartoma was found in most of the cases (79%) with combined dacrystic seizures and gelastic seizures, whereas it was found in one case (16%) with dacrystic seizures alone. The other underlying lesions in children with dacrystic seizures alone were subependymal nodules and cortical hamartomas (17%), left mesial temporal sclerosis (33%), and cortical dysplasia (17%). Regarding outcome, antiepileptic drugs alone achieved seizure freedom in four cases (22%) only and others (78%) were difficult to treat cases excluding three cases where treatments were not mentioned. Six cases underwent surgical intervention and two cases received ablative radiotherapy. Lesional dacrystic epilepsy is predominant and pharmaco-resistant in children. However, antiepileptic drugs lead to achieving seizure remission in few cases.

Microsurgical Management of Complex Hypothalamic Hamartomas in the Era of Minimally Invasive Therapy: A Case Series and Narrative Review

IntroductionRecently, there has been a paradigm shift in the management of hypothalamic hamartoma (HH) from traditional microsurgical techniques to less invasive alternatives such as stereotactic radiosurgery and laser interstitial thermal therapy. However, large and extensive HH may fail to respond to minimally invasive therapies, ultimately necessitating microsurgery.MethodsAll patients who underwent microsurgical resection of a complex HH by the 2 senior authors (D.J.L., H.L.R.) in 2011-2017 were included. Charts were retrospectively reviewed and demographic, clinical, imaging, and outcome data were recorded.Results8 patients, 7 children and 1 adult, with a mean age of 7 years (10 months-27 years), were included. Of those, 2 had failed previous treatments. All 7 children presented with pharmacoresistant gelastic seizures and cognitive dysfunction, 6 exhibited central precocious puberty, and 3 had behavioral problems. Other seizure types affected 6/8 patients. Mean lesion size was 21.6 mm (14-31), all with interpeduncular extension and 5 with intraventricular extension (Delalande type I: 3, type III: 4, type IV: 1). A frontotemporal orbitozygomatic (FTOZ) approach with optic nerve decompression was used in all patients, supplemented by another approach in 3 (endoscopic transventricular: 3, transcallosal: 1). Gross total resection was achieved in 6 patients and subtotal resection in 2. Transient complications occurred in 3 patients (37.5%): self-limited sodium imbalance (n=3), subdural hygroma (n=2). Permanent complications occurred in 2 patients (25%): perforator infarct (n=1), short-term memory loss (n=1). All patients experienced seizure resolution postoperatively with preserved hypothalamic-pituitary axis function. After a mean follow-up of 41 months (2-66), 7 patients remain seizure-free, while 1 has rare recurrent seizures. Cognitive and behavioral symptoms improved significantly in all patients.ConclusionFor large HH with interpeduncular extension, microsurgery via the FTOZ approach is a safe and highly effective treatment modality.

Case Report: Whole-Exome Sequencing of Hypothalamic Hamartoma From an Infant With Pallister-Hall Syndrome Revealed Novel de novo Mutation in the GLI3

Background: GLI-Kruppel family member 3 (GLI3), a zinc finger transcription factor of the sonic hedgehog pathway, is essential for organ development. Mutations in GLI3 cause several congenital conditions, including Pallister-Hall syndrome (PHS), which is characterized by polydactyly and hypothalamic hamartoma. Most patients are diagnosed soon after birth, and surgical removal of hypothalamic hamartoma in the very young is rarely performed because of associated risks.Case presentation: A 7-month-old boy with PHS features, including a suprasellar lesion, bifid epiglottis, tracheal diverticulum, laryngomalacia, left-handed polydactyly and syndactyly, and omental hernia was referred to our service. His suprasellar lesion was partially removed, and whole-exome sequencing was applied to the resected tumor, his peripheral blood, and blood from his parents. Histopathology confirmed the diagnosis of hypothalamic hamartoma, and molecular profiling revealed a likely pathogenic de novo variant, c.2331C>G (p. H777Q), in GLI3. Magnetic resonance imaging follow-up 1 year later showed some residual tumor, and the patient experienced normal development post operation.Conclusions: We presented a case of PHS that carries a novel GLI3 variant. Hypothalamic hamartoma showed a distinct genetic landscape from germline DNA. These data offer insights into the underlying etiology of hypothalamic hamartoma development in patients with PHS.

Central Precocious Puberty in a Three-Year-Old Girl

Precocious puberty is defined as the onset of secondary sexual characteristics before 8 years of age in girls and 9 years in boys. Central Precocious Puberty (CPP) is caused by early activation of the hypothalamic-pituitary-gonadal axis. Laboratory test of LH, FSH, and Estradiol is recommended for monitoring suppressive effects from GnRHa therapy in the early three months and every six months. This study aimed to report a case of CPP in a 3-year and 3-month-old girl. A 3-year and 3-month-old girl went to the hospital with vaginal bleeding (menstruation), breast development, and pubic and axilla hair for 7-month-old. Physical examination found moderately ill with obesity, body weight 20 kg, height 98 cm. Tanner stage was A2M3P2, café au lait was found in the left forehead with size 7x3.5 cm. In March 2015 before GnRHa therapy, LH, FSH and Estradiol level increased with levels of 4.32 mlU/mL, 6.01 mlU/mL, and 67 pg/mL, and after 3 months of the treatment was 0.87 mlU/mL, 2.51 mlU/mL and <20 pg/mL. Pelvic ultrasonography showed suggestive precocious puberty, bone age 5-year and 9-month (Greulich and Pyle), CT-Scan of the brain showed hypothalamic tumor suspected hypothalamic hamartoma. This patient was treated with a GnRHa injection every 4 weeks. Leuprorelin is a synthetic non-peptide analogue of natural GnRH. The diagnosis was based on medical history, physical examination, laboratory, and radiological findings. The prognosis of the patient was good.