Acquired hypothalamic obesity: A clinical overview and update.

Hypothalamic obesity (HO) is a rare and complex disorder that confers substantial morbidity and excess mortality. HO is a unique subtype of obesity characterized by impairment in the key brain pathways that regulate energy intake and expenditure, autonomic nervous system function, and peripheral hormonal signalling. HO often occurs in the context of hypothalamic syndrome, a constellation of symptoms that follow from disruption of hypothalamic functions, for example, temperature regulation, sleep-wake circadian control, and energy balance. Genetic forms of HO, including the monogenic obesity syndromes, often impact central leptin-melanocortin pathways. Acquired forms of HO occur as a result of tumours impacting the hypothalamus, such as craniopharyngioma, surgery or radiation to treat those tumours, or other forms of hypothalamic damage, such as brain injury impacting the region. Risk for severe obesity following hypothalamic injury is increased with larger extent of hypothalamic damage or lesions that contain the medial and posterior hypothalamic nuclei that support melanocortin signalling pathways. Structural damage in these hypothalamic nuclei often leads to hyperphagia, central insulin and leptin resistance, decreased sympathetic activity, low energy expenditure, and increased energy storage in adipose tissue, the collective effect of which is rapid weight gain. Individuals with hyperphagia are perpetually hungry. They do not experience fullness at the end of a meal, nor do they feel satiated after meals, leading them to consume larger and more frequent meals. To date, most efforts to treat HO have been disappointing and met with limited, if any, long-term success. However, new treatments based on the distinct pathophysiology of disturbed energy homeostasis in acquired HO may hold promise for the future.

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.

Postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement in patients with childhood-onset craniopharyngioma.

Objective: Hypothalamic-pituitary axis dysfunction is a common complication in post-operative craniopharyngioma(CP) patients, and it greatly impacts the long-term quality of life of such patients. To better understand the effects of postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement therapy in patients with childhood CP, we assessed approximately 200 patients with childhood-onset CP postoperatively. Methods: Clinical details of patients with childhood-onset CP who underwent sellar tumor resection in Beijing Children's Hospital and Beijing Tiantan Hospital from 2018 to 2019 were retrieved retrospectively. The participants were followed up to assess the effects of post-operative long-term hormone replacement therapy and assess the tumor recurrence rate. Results: The median age of admission was 8.1 (1.8, 14.3) years. Headache (45.5%), visual impairment (39.5%), and nausea (33.0%) were the most common clinical manifestations. ACP accounted for 95% of all CP cases. The incidence of central adrenal insufficiency and central hypothyroidism within the first week after surgery was 56.2% and 70.3%, respectively. At the same time 85.5% of the patients required at least one dose of desmopressin to control urine output. Total survival and tumor recurrence rates were 98.6% and 26.1%, respectively, with a median follow-up time of 29.7 (19.0, 40.3) months. During the follow-up period, 28.1% patients met the diagnostic criteria for short stature, while 54.4% fit the criteria for obesity. In addition, 94.4% of the patients were taking at least one kind of hormone substitution, and 74.7% were taking three or more. The prevalence of levothyroxine, glucocorticoid, desmopressin, and growth hormone replacement therapy was 87.3%, 77.5%, 78.9% and 31.0%, respectively. The proportion of patients treated with the substitutive combination of levothyroxine, hydrocortisone, and desmopressin was 54.9%. Conclusion: This study is a large-sample systematic postoperative endocrine function evaluation of patients with childhood-onset CP. Due to the high prevalence of post-operative hypothalamic-pituitary dysfunction, patients with CP usually require long-term multiple hormone substitution therapy. Individualized management and accurate hormone replacement dosage for postoperative childhood-onset CP patients are of great importance.

Seizure outcomes and safety profiles of surgical options for epilepsy associated to hypothalamic hamartomas. A systematic review and meta-analysis.

PURPOSE: Several surgical options are available for treating hypothalamic hamartoma-related epilepsy but their respective efficacy and safety profiles are poorly defined. METHODS: A literature search identified English-language articles reporting series of patients (minimum 3 patients with a follow-up ≥12 months) operated on by either microsurgery, endoscopic surgery, radiosurgery, radiofrequency thermocoagulation or laser interstitial thermal therapy for hypothalamic hamartoma-related epilepsy. The unit of analysis was each selected study. Pooled rates of seizure freedom and of neurological and endocrinological complications were analyzed using meta-analysis to calculate both fixed and random effects. The results of meta-analyses were compared. RESULTS: Thirty-nine studies were included. There were 568 and 514 participants for seizure outcome and complication analyses, respectively. The pairwise comparison showed that: i) the proportion of seizure-free cases was significantly lower for radiosurgery as compared to microsurgery, radiofrequency thermocoagulation and laser ablation, and significantly lower for endoscopic surgery as compared to radiofrequency thermocoagulation; ii) the proportion of permanent hypothalamic dysfunction was significantly higher for microsurgery as compared to all other techniques, and significantly lower for endoscopic surgery as compared to radiofrequency thermocoagulation and laser ablation; iii) the incidence of permanent neurological disorders was significantly higher for microsurgery as compared to endoscopic surgery, radiosurgery and radiofrequency thermocoagulation, and significantly lower for radiosurgery as compared to laser ablation. CONCLUSIONS: Minimally invasive surgical techniques, including endoscopic surgery, radiofrequency thermocoagulation and laser ablation, represent an acceptable compromise between efficacy and safety in the treatment of hypothalamic hamartoma-related epilepsy. Microsurgery and radiosurgery should be considered in carefully selected cases.

Treatment of hypothalamic obesity in people with hypothalamic injury: new drugs are on the horizon.

Hypothalamic obesity (HO) is a complex and rare disorder affecting multiple regulatory pathways of energy intake and expenditure in the brain as well as the regulation of the autonomic nervous system and peripheral hormonal signaling. It can be related to monogenic obesity syndromes which often affect the central leptin-melanocortin pathways or due to injury of the hypothalamus from pituitary and hypothalamic tumors, such as craniopharyngioma, surgery, trauma, or radiation to the hypothalamus. Traditional treatments of obesity, such as lifestyle intervention and specific diets, are still a therapeutic cornerstone, but often fail to result in meaningful and sustained reduction of body mass index. This review will give an update on pharmacotherapies of HO related to hypothalamic injury. Recent obesity drug developments are promising for successful obesity intervention outcomes.

Functional Hypothalamic Amenorrhea and Preclinical Cardiovascular Disease.

CONTEXT: Endothelial dysfunction is a preclinical cardiovascular disease (CVD) marker. Due to various neuroendocrine aberrations, functional hypothalamic amenorrhea (FHA) may be a sex-specific risk factor for CVD in young women. OBJECTIVE: To investigate endothelial function in women with FHA, compared with eumenorrheic controls and recently menopausal women. METHODS: We performed a cross-sectional analysis among women with FHA (n = 30), eumenorrheic controls (n = 29), and recently menopausal women (n = 30). FHA was defined as amenorrhea ≥3 consecutive months, estradiol <50 pg/mL, follicle-stimulating hormone (FSH) < 10 mIU/mL, and luteinizing hormone (LH) < 10 mIU/mL, excluding other etiologies. Participants were recruited through obstetrics and gynecology referrals, social media advertising, and review of electronic health records. Preclinical CVD was measured using EndoPAT 2000 to calculate reactive hyperemic index (RHI). RHI ≤1.67 indicates endothelial dysfunction. RESULTS: Mean estradiol levels in women with FHA, as compared with eumenorrheic controls and recently menopausal women, were 29.0 ± 18.1, 46.4 ± 15.7, and 10.9 ± 14.4 pg/mL (P < .0001), respectively. Women with FHA had lower insulin (P = .0095) and higher cortisol (P = .0004) compared with controls. RHI was significantly lower in women with FHA compared with eumenorrheic controls and recently menopausal women (1.8 ± 0.5 vs 2.2 ± 0.5 vs 2.2 ± 0.6, respectively; P = .008), and 35% of women with FHA had RHI ≤1.67, consistent with endothelial dysfunction. CONCLUSION: These results demonstrate endothelial dysfunction in 1 out of 3 young women with FHA. FHA may be a contributor to preclinical CVD, and it is not explained by hypoestrogenemia alone.

Long term outcome after surgical treatment for hypothalamic hamartoma.

PURPOSE: To determine long-term outcome for seizure control and clinical predictors for seizure freedom in patients undergoing surgical treatment for epilepsy associated with hypothalamic hamartoma (HH). METHODS: 155 patients underwent surgical treatment for HHs and treatment-resistant epilepsy at one center (Barrow Neurological Institute at St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA) between February 2003 and June 2010. Data collection included medical record review and direct follow-up interviews to determine seizure outcome. Statistical analysis included descriptive summaries of patient characteristics and time-to-event analysis for seizure freedom. RESULTS: Long-term survival with follow-up of at least five years since first surgical treatment was available for 108 patients (69.7% of the treatment cohort). The surgical approach for first HH intervention consisted of transventricular endoscopic resection (n = 57; 52.8%), transcallosal interforniceal resection (n = 35; 32.4%), pterional resection (n = 7; 6.5%), and gamma knife radiosurgery (n = 9; 8.3%). Multiple surgical procedures were required for 39 patients (36.1%). There were 10 known deaths from all causes in the treatment cohort (6.5%). Of these, one (0.6%) was related to immediate complications of HH surgery, three (1.9%) were attributed to Sudden Unexpected Death in Epileptic Persons (SUDEP), and one (0.6%) to complications of status epilepticus. For surviving patients with long-term follow-up, 55 (50.9%) were seizure-free for all seizure types. Univariable analysis showed that seizure-freedom was related to 1) absence of a pre-operative history for central precocious puberty (p = 0.01), and 2) higher percentage of HH lesion disconnection after surgery (p = 0.047). Kaplan-Meier survival analysis shows that long-term seizure outcome following HH surgery is comparable to short-term results. SUMMARY: These uncontrolled observational results show that long-term seizure control following HH surgical treatment is comparable to other forms of epilepsy surgery. Late relapse (at least one year after surgery) and SUDEP do occur, but in a relatively small number of treated patients. These results inform clinical practice and serve as a comparable benchmark for newer technologies for HH surgery, such as magnetic resonance imaging-guided laser interstitial thermal therapy, where long-term outcome results are not yet available.

Characteristics and factors influencing hypothalamic pituitary dysfunction in patients with craniopharyngioma.

Background: Craniopharyngioma is a benign tumor originating from the sellar region. Damages in this area caused by the tumor itself, surgery, or radiotherapy may result in severe hypothalamic-pituitary dysfunction (HPD) and eventually lead to a significant impairment in the long-term quality of life of patients. This study aimed to investigate the characteristics of HPD in patients with adamantinomatous craniopharyngioma (ACP) or papillary craniopharyngioma (PCP) and to identify the factors affecting HPD after surgery. Methods: In this single-center retrospective study, a total of 742 patients with craniopharyngioma were included. The neuroendocrine function of these patients before and after surgery was investigated. The differences in hypothalamic-pituitary function between the ACP and PCP groups were compared. The factors influencing the aggravation of HPD after surgery were identified. Results: The median follow-up after surgery was 15 months. Before surgery, the proportion of patients with diabetes insipidus (DI) and hyperprolactinemia in the PCP group was significantly higher than that in the ACP group (P<0.01), and the proportion of patients with adrenocortical hypofunction in the PCP group was significantly lower than that in the ACP group (P=0.03). Most cases of ACP originated in the sellar region, while most cases of PCP originated in the suprasellar region (P<0.01). More patients experienced adenohypophyseal hypofunction, DI, and hypothalamic obesity at postoperative follow-up than at onset in both the ACP and PCP groups (both P<0.01), with a higher increase observed in the ACP group (P<0.01). Older age at CP onset, tumor recurrence or progression, and ACP type were risk factors for postoperative aggravation of HPD in CP patients. Conclusion: Surgical treatment significantly aggravated HPD in both the ACP and PCP groups, but the specific characteristics and risk factors leading to aggravation were different between the two groups.

Epilepsy surgery in patients with hypothalamic hamartomas - Population-based two-year and long-term outcomes.

OBJECTIVE: Hypothalamic hamartomas are benign lesions associated with drug resistant epilepsy. Surgical treatment has become an increasingly utilised approach with promising results. This study aims to evaluate seizure outcome and complications after surgery in a population-based series of patients with intractable epilepsy and hypothalamic hamartoma. METHODS: All patients with hypothalamic hamartoma treated with epilepsy surgery in Sweden since 1995 with at least two years of follow-up were included. Preoperative, two-, five- and ten-year prospective longitudinal data were collected from The Swedish National Epilepsy Surgery Register. Data included seizure types and frequency, duration of epilepsy, clinical characteristics, neurological deficits, cognitive level and complications. In a subgroup from Gothenburg, we also analysed data not included in the register such as classification of hamartomas, surgical procedures and gelastic seizures. RESULTS: Eighteen patients were operated on during the period 1995-2020. The median age at epilepsy onset was 6 months and age at surgery 13 years. Four were seizure free and another four had ≥75% reduction in seizure frequency at the two-year follow-up. Two of the 13 patients with a long-term follow-up (five or ten years) were seizure-free and four had ≥75% reduction in seizure frequency. Three had an increased seizure frequency. No major complications were seen. Five had minor complications. In the Gothenburg subgroup all had open pterional disconnection or intraventricular endoscopic disconnection. Six of 12 were free from gelastic seizures at the two-year follow-up and six of eight at the long-term follow-up. CONCLUSION: This study supports surgical treatment of hypothalamic hamartomas as a safe method with a low risk of permanent complications. The seizure reduction seems to be persistent over time.

Epilepsy in hypothalamic hamartomas: semiology spectrum and predictor analyses of 78 patients.

OBJECTIVE: To assess seizure semiology and disease evolution in a large number of hypothalamic hamartoma (HH) patients. METHODS: Seizure semiology and associated medical records for 78 patients with HH-related epilepsy were retrospectively reviewed. Potential predictors of seizure types were assessed through univariate and binary logistic regression analyses. RESULTS: 57 (73.1%) patients presented with gelastic seizures at the onset of epilepsy, of whole 39 (68.4%) experienced additional seizure types with a mean latency interval of 4.59 years. Automatism, version, and sGTCs were increasingly common with disease evolution. The intraventricular size of HH was significantly negatively correlated with the disease evolution interval (r = -0.445, p = 0.009). A significantly higher rate of patients with automatism in the DF-II group relative to the DF-III group was found in both χ2 (X = 6.07, p = 0.014) and logistic regression analyses (B = 3.196, p = 0.020). INTERPRETATION: Gelastic seizures are the most common initial seizure type in HH patients, but variable semiologies occur with disease evolution. The intraventricular HH lesion size is an important determinant of epilepsy evolution. DF-II HH lesions contribute to a higher chance of automatism evolution. The present study furthers our understanding of the dynamic organization of the seizure network affected by HH.

Kindling in humans: Does secondary epileptogenesis occur?

The relevance of secondary epileptogenesis for human epilepsy remains a controversial subject decades after it was first described in animal models. Whether or not a previously normal brain region can become independently epileptogenic through a kindling-like process has not, and cannot, be definitely proven in humans. Rather than reliance on direct experimental evidence, attempts to answering this question must depend on observational data. In this review, observations based largely upon contemporary surgical series will advance the case for secondary epileptogenesis in humans. As will be argued, hypothalamic hamartoma-related epilepsy provides the strongest case for this process; all the stages of secondary epileptogenesis can be observed. Hippocampal sclerosis (HS) is another pathology where the question of secondary epileptogenesis frequently arises, and observations from bitemporal and dual pathology series are explored. The verdict here is far more difficult to reach, in large part because of the scarcity of longitudinal cohorts; moreover, recent experimental data have challenged the claim that HS is acquired consequent to recurrent seizures. Synaptic plasticity more than seizure-induced neuronal injury is the likely mechanism of secondary epileptogenesis. Postoperative running-down phenomenon provides the best evidence that a kindling-like process occurs in some patients, evidenced by its reversal. Finally, a network perspective of secondary epileptogenesis is considered, as well as the possible role for subcortical surgical interventions.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD): a collaborative review of the current understanding.

PURPOSE: To provide an overview of the discovery, presentation, and management of Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD). To discuss a search for causative etiology spanning multiple disciplines and continents. METHODS: The literature (1965-2022) on the diagnosis, management, pathophysiology, and potential etiology of ROHHAD was methodically reviewed. The experience of several academic centers with expertise in ROHHAD is presented, along with a detailed discussion of scientific discovery in the search for a cause. RESULTS: ROHHAD is an ultra-rare syndrome with fewer than 200 known cases. Although variations occur, the acronym ROHHAD is intended to alert physicians to the usual sequence or unfolding of the phenotypic presentation, including the full phenotype. Nearly 60 years after its first description, more is known about the pathophysiology of ROHHAD, but the etiology remains enigmatic. The search for a genetic mutation common to patients with ROHHAD has not, to date, demonstrated a disease-defining gene. Similarly, a search for the autoimmune basis of ROHHAD has not resulted in a definitive answer. This review summarizes current knowledge and potential future directions. CONCLUSION: ROHHAD is a poorly understood, complex, and potentially devastating disorder. The search for its cause intertwines with the search for causes of obesity and autonomic dysregulation. The care for the patient with ROHHAD necessitates collaborative international efforts to advance our knowledge and, thereby, treatment, to decrease the disease burden and eventually to stop, and/or reverse the unfolding of the phenotype.

Selective surgical mamillo-thalamic tract disconnection in hypothalamic hamartoma results in complete disappearance of gelastic seizures.

Hypothalamic hamartoma is a less common condition characterized by the several types of epileptic seizures including the gelastic type. It is reported that gelastic seizures are resistant to medical treatment with anticonvulsants, while stereotactic thermocoagulation or Gamma Knife radiosurgery are effective for seizure control. Here, we report an individual case where direct surgical resection disconnecting hypothalamic hamartoma from mammillothalamic tract resulted in complete disappearance of gelastic seizures without deterioration of cognitive function. A 6-year-old boy developed gelastic seizures at the age of 2 and suffered from precocious puberty. Anticonvulsants including carbamazepine and zonisamide failed to control seizures. The patient underwent direct division of the mammillothalmic tract by removal of hypothalamic hamartoma partially via anterior interhemispheric approach. It was observed that gelastic seizures disappeared completely after the surgical treatment without any endocrine and cognitive dysfunction for a follow-up period of 14 years. The mammillothalamic tract which connects anterior nucleus of thalamus and mammillary bodies plays a key role in gelastic seizures related to hypothalamic hamartoma. In this case, we disconnected the hamartoma specifically from the mammillary bodies and not from the rest of hypothalamus. Effectively, it enabled permanent control of seizures. This result shows that fibers connecting other hypothalamic structures and the dorsomedial nucleus of thalamus are not involved in gelastic seizure propagation from the hypothalamic hamartoma. When surgical treatment of hypothalamic hamartomas is performed it has high morbidity associated with hypothalamic disorders. Therefore, disconnection between hypothalamic hamartoma and mammillary bodies presents a possibility of reducing hypothalamic damage. Surgical disconnection between hamartoma and mammillothalamic tract carries minimal hypothalamic injury risk and our results suggest that it has the potential of seizure control for intractable gelastic seizures with less complications.

Isolated anterior pituitary dysfunction in adulthood.

Hypopituitarism is defined as a complete or partial deficiency in one or more pituitary hormones. Anterior hypopituitarism includes secondary adrenal insufficiency, central hypothyroidism, hypogonadotropic hypogonadism, growth hormone deficiency and prolactin deficiency. Patients with hypopituitarism suffer from an increased disability and sick days, resulting in lower health status, higher cost of care and an increased mortality. In particular during adulthood, isolated pituitary deficits are not an uncommon finding; their clinical picture is represented by vague symptoms and unclear signs, which can be difficult to properly diagnose. This often becomes a challenge for the physician. Aim of this narrative review is to analyse, for each anterior pituitary deficit, the main related etiologies, the characteristic signs and symptoms, how to properly diagnose them (suggesting an easy and reproducible step-based approach), and eventually the treatment. In adulthood, the vast majority of isolated pituitary deficits are due to pituitary tumours, head trauma, pituitary surgery and brain radiotherapy. Immune-related dysfunctions represent a growing cause of isolated pituitary deficiencies, above all secondary to use of oncological drugs such as immune checkpoint inhibitors. The diagnosis of isolated pituitary deficiencies should be based on baseline hormonal assessments and/or dynamic tests. Establishing a proper diagnosis can be quite challenging: in fact, even if the diagnostic methods are becoming increasingly refined, a considerable proportion of isolated pituitary deficits still remains without a certain cause. While isolated ACTH and TSH deficiencies always require a prompt replacement treatment, gonadal replacement therapy requires a benefit-risk evaluation based on the presence of comorbidities, age and gender of the patient; finally, the need of growth hormone replacement therapies is still a matter of debate. On the other side, prolactin replacement therapy is still not available. In conclusion, our purpose is to offer a broad evaluation from causes to therapies of isolated anterior pituitary deficits in adulthood. This review will also include the evaluation of uncommon symptoms and main etiologies, the elements of suspicion of a genetic cause and protocols for diagnosis, follow-up and treatment.

Diencephalic syndrome-like presentation of brainstem tumor: a series case-based review.

PURPOSE: Russel described a rare clinical entity known as diencephalic syndrome (DS) in 1951, which was traditionally caused by a neoplasm in the hypothalamic-optic chiasmatic region. DS is characterized by severe emaciation despite adequate or slightly reduced caloric intake, locomotor hyperactivity, euphoria and other minor features. Current evidence suggests that a rare population of children with a similar phenotype may have their tumor located in the posterior fossa instead, defining the DS-like presentation, a rare entity with few cases reported in the literature. METHODS: A thorough search of three databases (PubMed, Ovid Medline, and Ovid Embase) was conducted to identify relevant papers reporting children with DS associated with brainstem tumors. To our knowledge, only seven cases have been documented in the literature. Moreover, we present four of our own cases, focusing on the unusual clinical presentation, the diagnosis process, and the lag time between the initial symptoms and the definitive diagnosis. RESULTS: In this review, the mean lag time between the onset of symptoms and diagnosis was 20.9 months (median: 16 months; range: 1.5-72 months), whereas in our series of cases, the time was 32.5 months (median: 33 months; range: 7-57 months). CONCLUSION: Despite recent significant advances in neuro-oncology diagnostic tools, this mean lag time did not improve when compared with the previous literature review from 1976. Throughout these data, we aim to raise awareness in the hopes of detecting intracranial neoplasms earlier in cases of children with profound emaciation of unknown cause.

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.

Psychological factors in functional hypothalamic amenorrhea: A systematic review and meta-analysis.

Background: Psychological factors have been found to be associated with functional hypothalamic amenorrhea (FHA); however, their role in the onset or persistence of FHA is still understudied. The study aims to assess the associations of psychological factors with the presence vs the absence of FHA. Methods: A systematic literature search has been conducted across the major databases (PubMed, PsycINFO, Scopus, and Embase) to explore the psychological factors associated with FHA. The search was limited to English-written articles published from 2000 onwards. Articles were selected based on stringent inclusion/exclusion criteria. After data extraction, meta-analysis and meta-synthesis were conducted. Results: Of 349 retrieved articles, eight studies were included. Findings indicate that the main psychological factors associated to FHA seem to be depression and eating attitudes, especially drive for thinness. FHA women present higher levels of anxiety, sleep disorders, dysfunctional attitudes, and alexithymia. The meta-analysis on drive for thinness revealed that the pooled MD across the studies was statistically significant both in the fixed 0.63 (95% CI: 0.31-0.95) and random model 0.70 (95% CI: 0.13-1.26). Likewise, as for depression, the pooled MD across the studies was statistically significant both in the fixed 0.60 (95% CI: 0.36-0.84) and random model 0.61 (95% CI: 0.20-1.01). Discussion: Findings showed the association of psychological factors and FHA and recognized their involvement in the persistence of the disorder. A multidisciplinary approach should involve a collaborative process between gynecologists, clinical psychologists, and psychiatrists, from diagnosis to treatment. Longitudinal studies should be implemented with a comparison/control group or by including clinical psychologists in the psychological assessment and study design.

Rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome - neuro-endocrine tumours (ROHHAD-NET): case series and learning points.

OBJECTIVES: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, autonomic dysregulation (ROHHAD) is a rare syndrome associated with high morbidity and mortality. Diagnosis is often challenging. We describe three cases of ROHHAD with heterogeneous presentations but some consistent clinical features, including hyperprolactinaemia at diagnosis. We highlight when the diagnosis of ROHHAD should be considered at an early stage. CASE PRESENTATION: All three patients presented between 4 and 6 years old with rapid-onset obesity. They all have central hypoventilation requiring nocturnal BiPAP, varying degrees of hypothalamic dysfunction with hyperprolactinaemia being a consistent feature, and autonomic dysfunction. One patient has a neuro-endocrine tumour (NET) and two have glucose dysregulation. CONCLUSIONS: High prolactin was a consistent early feature. Central hypoventilation and NET may present later and therefore regular sleep studies and screening for NETs are required. A high suspicion of ROHHAD is warranted in patients with rapid, early-onset obesity and hyperprolactinaemia without structural pituitary abnormality.

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.