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Hypothalamic hamartomata (HH) not only are usually associated with drug-resistant epilepsy but can also cause precocious puberty and developmental delay. Gelastic seizures are the most common type of seizures. Magnetic resonance image (MRI)-guided laser interstitial thermal therapy (LiTT) is a technique whereby a laser fibre is stereotactically implanted into a target lesion and heat is used to ablate whilst tissue temperature is monitored using MRI thermography. MRI-guided LiTT has proven to be an effective and safe method to treat HH. To use the LiTT system, highly accurate stereotactic fibre implantation is required. This can be achieved by the use of frame-based or frameless neuronavigation techniques. However, these techniques generally involve rigid head immobilisation using cranial pin fixation. Patients need sufficient skull thickness to safely secure the pins and sufficient skull rigidity to prevent deformation. Hence, most of the clinical reports on the use of LiTT for children describe patients aged 2 years or older. We report a novel and practical technique of using a paste cast helmet to securely place a stereotactic frame in a 5-month-old infant with HH and drug-resistant epilepsy that allowed the successful application of MRI-guided LiTT.

Background: The syndrome of inappropriate antidiuretic hormone (SIADH) is usually treated with fluid restriction. This can be challenging in patients with obligate fluid intake for nutrition or medication. Pharmaceutical treatment with tolvaptan and urea is available but minimal paediatric data are available. We review the efficacy and safety of tolvaptan and urea in paediatric patients diagnosed with SIADH. Methods: Retrospective review of paediatric inpatients with clinical diagnosis of SIADH. Patients were identified from pharmacy records, based on tolvaptan and urea prescriptions. Relevant information was extracted from patient electronic records. The main outcome measures included: number of days to sodium normalisation, daily change in plasma sodium concentration and maximum increase of plasma sodium concentration in 24hrs . Reported side effects were also captured. Results: Tolvaptan use led to plasma sodium normalisation in 10/13 (77%) within six days (median 2.5 days, range [1,6]) with a median change of sodium concentration of 7 mmol/L (-1,14) within the first 24 hours of treatment. Three patients experienced a change in plasma sodium >10 mmol/l/day but had no apparent side effects. Urea use led to sodium normalisation in 5/6 (83%) patients. Median number of days to normalisation with urea was 2 (1,10) with a median change of plasma sodium concentration of 2 mmol/L (-1,6) within the first 24hours. All patients tolerated tolvaptan and/or urea without unexpected side effects. Conclusions: Tolvaptan and urea appear to be safe and effective when fluid restriction is challenging in paediatric SIADH.

Adrenal insufficiency (AI) is characterised by lack of cortisol production from the adrenal glands. This can be a primary adrenal disorder or secondary to adrenocorticotropic hormone deficiency or suppression from exogenous glucocorticoids. Symptoms of AI in children may initially be non-specific and include growth faltering, lethargy, poor feeding, weight loss, abdominal pain, vomiting and lingering illnesses. AI is treated with replacement doses of hydrocortisone. At times of physiological stress such as illness, trauma or surgery, there is an increased requirement for exogenous glucocorticoids, which if untreated can lead to an adrenal crisis and death. There are no unified guidelines for those

Despite high survival, paediatric optic pathway hypothalamic gliomas are associated with significant morbidity and late mortality. Those youngest at presentation have the worst outcomes. We aimed to assess presenting disease, tumour location, and treatment factors implicated in the evolution of neuroendocrine, metabolic, and neurobehavioural morbidity in 90 infants/children diagnosed before their third birthday and followed-up for 9.5 years (range 0.5–25.0). A total of 52 (57.8%) patients experienced endo-metabolic dysfunction (EMD), the large majority (46) of whom had hypothalamic involvement (H+) and lower endocrine event-free survival (EEFS) rates. EMD was greatly increased by a diencephalic syndrome presentation (85.2% vs. 46%, p = 0.001)), H+ (OR 6.1 95% CI 1.7–21.7, p 0.005), radiotherapy (OR 16.2, 95% CI 1.7–158.6, p = 0.017) and surgery (OR 4.8 95% CI 1.3–17.2, p = 0.015), all associated with anterior pituitary disorders. Obesity occurred in 25% of cases and was clustered with the endocrinopathies. Neurobehavioural deficits occurred in over half (52) of the cohort and were associated with H+ (OR 2.5 95% C.I. 1.1–5.9, p = 0.043) and radiotherapy (OR 23.1 C.I. 2.9–182, p = 0.003). Very young children with OPHG carry a high risk of endo-metabolic and neurobehavioural comorbidities which deserve better understanding and timely/parallel support from diagnosis to improve outcomes. These evolve in complex, hierarchical patterns over time whose aetiology appears predominantly determined by injury from the hypothalamic tumour location alongside adjuvant treatment strategies.

INTRODUCTION: Whilst most patients with PLGG will survive, varying morbidities derived from patient,tumour & treatment characteristics can afflict life-long disabling functional impairments. No PLGG studies have evaluated potential prognostic factors for important functional outcomes. METHODS: We performed retrospective analysis of all children diagnosed with PLGG at GOSH 1980-2021.Review of medical notes recorded patient demographics,tumour characteristics & treatment data.Functional outcomes included endocrine,educational,visual (in OPG),auditory & physical function.Multivariate regression analysis(p

Despite its small size, the hypothalamus is one of00 the most complex and vital structures of the human brain. Through its intimate connection with the pituitary gland and other areas of the brain, the hypothalamus acts as the master regulator of various neuroendocrine systems while integrating endocrine and neural signals which regulate superior functions such as appetite, thirst, circadian rhythms, arousal, memory, and behaviour. Consequently, acquired damage to or maldevelopment of this area can have widespread consequences on a variety of homeostatic mechanisms. Hypothalamic dysfunction can present with heterogeneous clinical features including hypopituitarism necessitating pituitary hormone replacement, a spectrum of weight disorders ranging from hypothalamic obesity to diencephalic syndrome/anorexia, temperature and sleep dysregulation, behavioural difficulties, and memory and autonomic dysfunction. Targeted treatment for hypothalamic obesity and the ‘non-endocrine’ manifestations of hypothalamic dysfunction has proven difficult, and supportive care and avoidance of acquired hypothalamic damage are the only strategies currently available for these patients.

BACKGROUND: Despite high survival, paediatric optic pathway hypothalamic gliomas are associated with significant morbidity and late mortality. Those youngest at presentation have the worst outcomes. METHODS: We aimed to assess presenting disease, tumour location and treatment factors implicated in the evolution of neuroendocrine, metabolic and neuro-behavioural morbidity in children diagnosed before their 3rd birthday and followed over four decades (1981- 2020). RESULTS: Ninety infants/young children followed-up for 9.5 years (range 0.5-25.0) were included in the study. Fifty-two (57.8%) patients experienced endo-metabolic dysfunction (EMD), the large majority (46) had hypothalamic involvement (H+) and lower endocrine event free survival (EEFS) rates. Median time to first endocrine event was 3.4 years, with EEFS declining up to 13.6 years after diagnosis. EMD was greatly increased by a diencephalic syndrome presentation (85.2% vs 46%, p=0.001), H+ (OR 6.1 95% CI 1.7 – 21.7, p 0.005), radiotherapy (OR 16.2, 95% CI 1.7 – 158.6, p=0.017) and surgery (OR 4.8 95% CI 1.3- 17.2, p=0.015), all associated with anterior pituitary disorders. Obesity occurred in 25% of cases and clustered with the endocrinopathies. Posterior pituitary disorders were recorded in 15 subjects (16.7%), only after surgery and/or as a consequence of hydrocephalus in those with suprasellar tumours and hypothalamic disease. Neuro-behavioural deficits occurred in over half (52) of the cohort and were associated with H+ (OR 2.5 95% C.I. 1.1 – 5.9, p=0.043) and radiotherapy (OR 23.1 C.I. 2.9 – 182, p=0.003). CONCLUSIONS: Very young children with OPHG carry a high risk of endo-metabolic and neuro-behavioural comorbidities which deserve better understanding and timely/parallel support from diagnosis to improve outcomes. These evolve in a complex hierarchical pattern overtime whose aetiology appears predominantly determined by injury from the hypothalamic tumour location alongside adjuvant treatment strategies.

INTRODUCTION: The number of children and young people (CYP) surviving brain tumours is increasing annually with a doubling of 5-year survival over the last 40 years. More than two-thirds of these survivors suffer multiple long-term co-morbidities (“late effects”) from their tumour and/ or treatment(s) necessitating lifelong multiprofessional follow-up. This results in multiple appointments and increases the burden of care on patients. Method/Project description To establish a collaborative multidisciplinary “one stop shop” long-term follow-up clinic for CYP >5 years from the end of neuro-oncological treatment to the reduce the need for multiple hospital appointments and to provide holistic assessment and care.The first clinic began in January 2020 as a collaboration between the departments of neuro-oncology, endocrinology, neuropsychology, psychology, physiotherapy and occupational therapy. RESULTS: We have audited the last 60 patients seen in clinic in 2 years and the services they required both in and out of clinic are noted below: Endocrinology – 58 patients Educational help and formal neuropsychology (44 and 39 respectively) There are significant emotional problems in the group and 32 saw clinical psychology and 13 were referred to CAMHS. Physical function issues – 31 saw both physiotherapy and occupational therapy. 10 required referral to orthopaedics Neurology and neurosurgery (13 and 11 respectively) Visual impairment – 33 saw ophthalmology Hearing problems – 17 saw audiology Other organ dysfunction – 4 saw cardiology and 3 urology. We have some feedback data on patient and parent satisfaction with the clinic which shows 92% (13 of 14) families preferred to be seen in the MDT setting rather than by separate clinicians. DISCUSSION: Few models of similar multidisciplinary neuro-oncology long-term follow-up clinics exist in the UK with a lack of streamlined funding, despite recognition from families and professionals about their utility.

Growth hormone (GH) deficiency (GHD) in children is defined as impaired production of GH by the pituitary gland that results in growth failure. This disease might be congenital or acquired, and occurs in isolation or in the setting of multiple pituitary hormone deficiency. Isolated GHD has an estimated prevalence of 1 patient per 4000-10,000 live births and can be due to multiple causes, some of which are yet to be determined. Establishing the correct diagnosis remains key in children with short stature, as initiating treatment with recombinant human GH can help them attain their genetically determined adult height. During the past two decades, our understanding of the benefits of continuing GH therapy throughout the transition period from childhood to adulthood has increased. Improvements in transitional care will help alleviate the consequent physical and psychological problems that can arise from adult GHD, although the consequences of a lack of hormone replacement are less severe in adults than in children. In this Review, we discuss the differential diagnosis in children with GHD, including details of clinical presentation, neuroimaging and genetic testing. Furthermore, we highlight advances and issues in the management of GHD, including details of transitional care.

Background: Short stature can be caused by mutations in a multitude of different genes. 3-M syndrome is a rare growth disorder marked by severe pre- and postnatal growth retardation along with subtle dysmorphic features. There have only been 2 prior reports of mutations in CCDC8 causing 3-M syndrome. Methods: Two patients presenting with mild short stature underwent whole exome sequencing. The mutation was confirmed via Sanger sequencing. We compare the clinical characteristics of our 2 patients to patients previously reported with mutations in the same gene. Results: Exome sequencing identified a homozygous frameshift mutation in CCDC8 in both patients. They presented with a much milder phenotype than previously described patients with the same mutation. Conclusion: In this study, we report a case of 2 sisters with relatively mild short stature who were found via exome sequencing to carry a previously reported homozygous mutation in CCDC8. These patients expand the anthropometric phenotype of 3-M syndrome and demonstrate the power of exome sequencing in the diagnosis of children with short stature. 3-M syndrome should be considered in children with mild skeletal abnormalities, normal/high growth hormone-IGF axis parameters, and normal intelligence.

Background/Introduction: The European Registry for Rare Bone and Mineral Conditions (EuRR-Bone) was founded in April 2020 and is the affiliated registry of the European Reference Network for Rare Bone Diseases (ERN BOND). Purpose: As bone and mineral conditions are seen by a variety of specialists there is a close connection with the European Registries for Rare Endocrine Conditions (EuRRECa) and its affiliated ERN Rare Endocrine Diseases (Endo-ERN). EuRR-Bone is open not only to centres within these ERNs but also to others and consists of a core registry for all cases and an e-reporting registry for new cases. Methods: The latter is accomplished via an electronic reporting platform, e-REC (e-Reporting of Rare Conditions), a light touch approach that does not collect personally identifiable information. Unique IDs for reported cases are generated instantaneously and emailed to users to be stored locally at reporting centres. Data are available to all collaborators following approval by the joint Data Access Committee of EuRRECa and EuRR-Bone. Results: Until July 2020, 12 centres from 9 different countries joined, of which 5 are ERN BOND members and 10 are Endo-ERN members. A total of 23 adults and 20 children were newly diagnosed with a Bone and Mineral condition. Amongst adults, the most frequently reported conditions were fibrous dysplasia and PTH independent hypercalcemia, while in children pseudohypoparathyroidism and osteogenesis imperfecta were the most reported. Since April 2020, the e-REC platform is also being used to capture the occurrence of a new COVID19 infection in a patient with an existing bone or mineral condition. Conclusion(s): e-REC is a promising tool enabling clinical networks to objectively map conditions and related activity, providing a better understanding of the occurrence of the rare bone and mineral conditions.

We present a non-consanguineous family of three siblings who presented with diabetes mellitus (DM), two of whom had genetically confirmed cystic fibrosis (CF), with one pancreatic-sufficient mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (ΔF508/R117H;IVS8-5T). A detailed history revealed family members from three successive generations diagnosed with ‘type 1’ or ‘type 2’ diabetes, leading to genetic investigations for monogenic DM. A heterozygous frameshift mutation in the hepatocyte nuclear factor 1 homeobox alpha (HNF1A) gene (c.404delA) was subsequently confirmed in all three siblings, which is known to cause monogenic diabetes and is exquisitely sensitive to sulfonylurea therapy. Following this diagnosis, both siblings with CF and HNF1A monogenic diabetes were started on gliclazide therapy, while their older brother who had been wrongly diagnosed with type 1 diabetes was switched from insulin to gliclazide, all with excellent therapeutic responses.

The involvement of the diencephalic regions in neuromyelitis optica spectrum disorder (NMOSD) may lead to endocrinopathies. In this study, we identified the following endocrinopathies in 60% (15/25) of young people with paediatric-onset aquaporin 4-Antibody (AQP4-Ab) NMOSD: morbid obesity ( n = 8), hyperinsulinaemia ( n = 5), hyperandrogenism ( n = 5), amenorrhoea ( n = 5), hyponatraemia ( n = 4), short stature ( n = 3) and central hypothyroidism ( n = 2) irrespective of hypothalamic lesions. Morbid obesity was seen in 88% (7/8) of children of Caribbean origin. As endocrinopathies were prevalent in the majority of paediatric-onset AQP4-Ab NMOSD, endocrine surveillance and in particular early aggressive weight management is required for patients with AQP4-Ab NMOSD.

Aims Although rare, craniopharyngiomas are the commonest suprasellar tumour in childhood. Despite high overall survival, children and young people Methods Clinical questions were formulated based on a PICO (Population, Intervention, Comparison, Outcome) format by a multidisciplinary Guideline Development Group. Systematic searches were conducted via the Ovid MEDLINE (1946-February 2017) and Cochrane Library (2016, Issue 12) databases, identifying 2023 separate research articles. Publications underwent a three-tier filtering process and 300 were reviewed using the GRADE approach. Where recommendations could not be made, a two-stage international Delphi consensus process was conducted. Results 44 clinical questions were identified, leading to 35 recommendations largely based on low to very low quality evidence. 30 further recommendations achieved >70% agreement via the Delphi consensus process. Important highlights include the recommendation that craniopharyngiomas are managed in tertiary paediatric centres with sufficient neuro-oncology, neurosurgery, endocrinology, radiology, pathology and neuropsychology multidisciplinary experience. At diagnosis, tumours should be graded using the ‘Paris’ grading system and subsequent surgical treatment tailored to avoid hypothalamic damage, with adjuvant upfront radiotherapy being offered where tumour resection is incomplete. Detailed recommendations on the neuroendocrine, ophthalmological and psychological pre-treatment assessment of patients and long-term follow-up of survivors are also made, with a review on the safety of growth hormone replacement therapy in this cohort. Conclusions These guidelines provide the first evidence- and consensus-based national recommendations for the management of paediatric craniopharyngioma, and highlight the need for further research in areas such as the efficacy of proton beam therapy, radiosurgery and intracystic therapies in children, and the management of late effects such as hypothalamic obesity. Through their implementation, we hope to achieve better consistency in the quality of care of such patients and improve long-term quality of survival.

Fifty percent of pediatric low-grade gliomas affect the optic pathway, hypothalamus, and suprasellar areas (OP/HSGs), resulting in significant long-term neuroendocrinopathy.This study aimed to dissect tumor- from treatment-related risk factors for OP/HSG-associated neuroendocrinopathy.This was a retrospective case notes analysis of 166 children with newly diagnosed OP/HSGs at our quaternary center between 1980 and 2010 by multivariate Cox, linear, and logistic regression.Patients were of median (range) age 4.9 (0.2-15.4) years at diagnosis and followed up for 8.3 (0.04-26.8) years. Despite high 20-year overall survival (81.0%), progression-free and endocrine event-free survival (EEFS) were 47.2 and 20.8%, respectively. EEFS declined up to 15 years post-diagnosis, with hypothalamic involvement (P.001) being implicated more than radiotherapy (P = .008) in earlier endocrinopathy; the reverse being true of its density (radiotherapy P.001; hypothalamic involvement P = .006). GH deficiency (GHD) was most common (40.3%), followed by central precocious puberty (CPP, 26.0%), gonadotropin (GnD; 20.4%), TSH (13.3%), and ACTH (13.3%) deficiencies. GHD increased with later treatment eras (P.01), but replacement did not increase progression. CPP was associated with future GnD (P.05). Posterior pituitary dysfunction (PPD; 7.2%) occurred in 57.9% after only biopsies or shunt procedures, and was associated with 6/13 deaths; 50.2% became obese. Tumor extent, surgery, and increased endocrinopathy, rather than radiotherapy, predicted visuocognitive morbidity.This first longitudinal OP/HSG-specific study demonstrates that hypothalamo-pituitary dysfunction evolves hierarchically over decades. Tumor location predicts its speed of onset and radiotherapy its density. GnD can evolve from previous CPP, whereas life-threatening PPD can occur after any surgery. Our data suggest that recent radiation-avoiding chemotherapeutic strategies have increased GHD without improving survival.

Unlike pilocytic astrocytomas in other parts of the brain, optic pathway gliomas (OPG) are usually diffuse lesions involving the anterior optic pathways and hypothalamus. Their infiltrative nature often precludes complete surgical resection. We sought to determine whether careful magnetic resonance (MR) analysis, correlated with visual deficits, could be sufficient to identify those focal lesions that may be amenable to more aggressive surgical resection at presentation. We retrospectively reviewed the medical records of patients from two sites: children under 20 years of age treated for OPG between 1985 and 2009 at St Jude’s Children’s Research Hospital and children under 16 years of age treated at Great Ormond Street Hospital, London, UK, between 1984 and 2011. Patients with isolated optic nerve tumors were excluded. Visual acuity and visual field data at presentation were reviewed and correlated with MR characteristics, including extent of optic pathway involvement, symmetry, and lateral extension. Two hundred and one children were treated for OPG between 1984 and 2011 in the two institutions; 74 had neurofibromatosis 1 (NF1). At presentation, visual loss was symmetrical in 132 patients and asymmetrical in 69. Potential correlation between pattern of visual loss and tumor characteristics on routine MRI was found in only 13 patients with asymmetrical vision. There was no difference between patients with and without NF1. The decision for aggressive surgical resection for optic pathway gliomas should be based on clinical criteria, particularly in children with good vision in one eye and poor vision in the other, as current MRI results do not reliably predict visual field deficits.

This article reports a case of a cerebellopontine angle epidermoid cyst presenting as isolated painful trigeminal neuropathy. The indolent nature of these uncommon benign tumors leads to frequent delays in their presentation and diagnosis, with patients often initially undergoing dental procedures. This is illustrated in the present case reported here, which highlights the difficulties in identifying trigeminal neuralgia (TN), particularly in its early phases, and supports current recommendations for routine neuroimaging in suspected cases of painful trigeminal neuropathy, which, unlike classic TN, is caused by a disorder other than neurovascular compression (even in the absence of additional neurologic symptoms or signs) and is present particularly in younger patients with atypical features. Additionally, this case report offers a unique patient perspective of living with TN, with a detailed description by one of the authors of the nature of the pain and its impact.

List of all NHS Trusts in England (excluding mental and community health trusts) and details of any seven-day service reorganisation occurring between 2012 to 2014. (DOCX 67 kb)

Despite their benign histology, craniopharyngiomas are the archetypal suprasellar tumour for causing hypothalamo-pituitary endocrine dysfunction both from tumour- and treatment-related effects. Endocrine deficits are frequently present at diagnosis but are often under-recognised; thus a detailed pre-treatment endocrine assessment is essential, particularly to exclude adrenocorticotrophic hormone deficiency and central diabetes insipidus prior to any surgery. Management of fluid balance in the perioperative period is particularly complex and requires the expertise of a paediatric endocrinologist familiar in managing patients with multiple endocrinopathies. Post-operatively, virtually all survivors face a lifetime risk of evolving endocrine deficits that may be extremely complex to manage, therefore requiring careful long-term follow-up and monitoring into adulthood with appropriate plans for transition between paediatric and adult care.

We can now cure more than 70 per cent of all childhood cancers, and this cure rate approaches 90 per cent for some tumours.1 Enhanced supportive care for dose-intense treatment regimens imposed on a cancer incidence that has been stable over the past 40 years2 is responsible for this success. Where survival is so high, however, further attempts to increase it must be balanced against the multi-organ toxicities to the majority of developing children. Though not necessarily impotent, 15–30 per cent of male survivors are rendered infertile,3 either from hypothalamo–pituitary–gonadal exposure to chemoradiation4 or from diseases such as Hodgkin’s lymphoma.5

BACKGROUND: Craniopharyngiomas are the commonest suprasellar tumour in childhood. Despite high overall survival, children with craniopharyngiomas are at risk of multiple relapses and long-term tumour- and treatment-related morbidity. We sought to provide, for the first time, a national evidence-based standard for best practice for the assessment, treatment, and follow-up of paediatric craniopharyngiomas. METHODS: 44 clinical questions were formulated based on a PICO (Population, Intervention, Comparison, Outcome) format by a multidisciplinary Guideline Development Group to guide systematic searches via the Ovid MEDLINE (1946-February 2017) and Cochrane Library (2016, Issue 12) databases, identifying 2023 separate research articles. Publications underwent a three-tier filtering process and 300 were reviewed using the GRADE approach. Where recommendations could not be made, a two-stage international Delphi consensus process was conducted. RESULTS: 35 recommendations were made, largely based on low to very low quality evidence. 30 further recommendations achieved >70% agreement via Delphi consensus. Craniopharyngiomas should be managed in tertiary paediatric centres with sufficient neuro-oncology, neurosurgery, endocrinology, radiology, pathology and neuropsychology experience. At diagnosis, tumours should be graded using the “Paris” grading system and surgical treatment tailored to avoid hypothalamic damage, with adjuvant radiotherapy being offered after incomplete resections. Recommendations on the long-term multidisciplinary follow-up of survivors are also detailed. CONCLUSIONS: These Royal College of Paediatrics and Child Health (RCPCH)-endorsed guidelines provide the first evidence-based national recommendations for the management of paediatric craniopharyngioma. Through their implementation, we hope to achieve better consistency in the quality of care of such patients and improve long-term quality of survival.