Neuroinflammation and Hypothalamo-Pituitary Dysfunction: Focus of Traumatic Brain Injury.

The incidence of traumatic brain injury (TBI) has increased over the last years with an important impact on public health. Many preclinical and clinical studies identified multiple and heterogeneous TBI-related pathophysiological mechanisms that are responsible for functional, cognitive, and behavioral alterations. Recent evidence has suggested that post-TBI neuroinflammation is responsible for several long-term clinical consequences, including hypopituitarism. This review aims to summarize current evidence on TBI-induced neuroinflammation and its potential role in determining hypothalamic-pituitary dysfunctions.

Sleep-disordered breathing, respiratory patterns during wakefulness and functional capacity in pediatric patients with rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation syndrome.

OBJECTIVE: To characterize the clinical presentation of sleep-disordered breathing and respiratory patterns at rest and during a 6-min walk test (6MWT) in children with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome. METHODS: Retrospective study of children with ROHHAD who had a diagnostic baseline polysomnography, daytime cardiorespiratory monitoring at rest and a 6MWT. Polysomnography data were also compared with body mass index-, age-, and sex-matched controls. RESULTS: Of the eight children with ROHHAD, all eight (100%) had obstructive sleep apnea (OSA) and 2/8 (25%) had nocturnal hypoventilation (NH) on their baseline polysomnography. Comparing the ROHHAD group to the control group, there were no significant differences in the median (interquartile range [IQR]) obstructive apnea-hypopnea index (11.1 [4.3-58.4] vs. 14.4 [10.3-23.3] events/h, respectively; p = .78). However, children with ROHHAD showed a significantly higher desaturation index compared to the control group (37.9 [13.7-59.8] vs. 14.7 [4.3-27.6] events/h; p = .05). While awake at rest, some children with ROHHAD experienced significant desaturations associated with central pauses. During the 6MWT, no significant desaturations were observed, but two children showed moderate functional limitation. CONCLUSIONS: Among children with ROHHAD, respiratory instability may be demonstrated by a significant number and severity of oxygen desaturations during sleep in the presence of OSA, with or without NH, and oxygen desaturations with central pauses at rest during wakefulness. Interestingly, during daily activities that require submaximal effort, children may not experience oxygen desaturations. Early recognition of respiratory abnormalities and targeted therapeutic interventions are important to limit associated morbidity and mortality in ROHHAD.

Significance of the electrophysiological border between hypothalamic hamartomas and the hypothalamus for the target of ablation surgery identified by intraoperative semimicrorecording.

OBJECTIVE: Ablation surgery has become the first line of treatment for hypothalamic hamartomas (HHs). For effective treatment, optimum targeting of ablation is mandatory. The present study aimed to evaluate the correspondence between the electrophysiological features of HHs and morphological targeting by semimicrorecording during stereotactic radiofrequency thermocoagulation (SRT). METHODS: Eighty HH patients who underwent SRT were involved. Semimicrorecording was performed on the first trajectory. The distance from the center of the target at the morphological border (TMB) determined by magnetic resonance imaging, differences in discharge patterns, and area potentials (APs) were measured. RESULTS: The electrophysiological border (EB) between the HH and hypothalamus was detected by semimicrorecording in 73 (91.3%), AP increase (API) in the HH was detected in 31 (38.8%), and spike discharges (SDs) of the HH were detected in 56 patients (70.0%). Semimicrorecording showed significantly different APs among structures passing through the trajectory, except between API and SDs. The median distances from the center of the TMB to the EB, API, SDs, and AP decline were -3.50, -2.49, -1.38, and +2.00 mm, respectively. SIGNIFICANCE: The electrophysiological features of HHs were shown by semimicrorecording during SRT. The EB corresponded to the morphological border. The electrophysiologically active area of HHs was located near the border. Ablation surgery should focus on disconnection at the border between the HH and the hypothalamus to maximize its effectiveness, as well as to reduce complications.

Correlación de evaluaciones clínicas e imagenológicos en casos con craneofaringioma: Hospital "Hermanos Ameijeiras" / Correlation between the clinical evaluations with the imaging classifications in cases with craniopharyngioma: "Hermanos Ameijeiras" Hospital

OBJETIVO: Determinar la correlación entre las evaluaciones clínicas de los estatus pituitario e hipotalámico con las clasificaciones imagenológicas de Kassam y Puget. MATERIAL Y MÉTODOS: Se realizó un estudio con diseño descriptivo, correlacional y retrospectivo, con una muestra por conveniencia de una población (N=1567) diagnosticada con tumores intracraneales en el Hospital "Hermanos Ameijeiras" de enero de 2014 a diciembre de 2018. Se incluyeron las variables: edad, sexo, manifestaciones clínicas, localización tumoral, estatus hipotalámico, estatus pituitario, características imagenológicas, compromiso hipotalámico y relación con el tallo pituitario. Los resultados se compararon y sistematizaron mediante métodos teórico y estadístico; se empleó el paquete InfoStat/L para Windows. RESULTADOS PRINCIPALES: Se incluyeron 44 casos con una edad media de 32±15,8 años, predominantemente féminas (61,4%). Las manifestaciones clínicas más comunes fueron cefalea (88,6%) y trastornos visuales (77,2%), con lesiones mayores a 2 cm de diámetro con ubicación supraselar (75,1%), estatus hipotalámico Grado II (45,5%) y estatus pituitario Grado IV (38,6%) todos con realce a la administración del contraste. La asociación más significativa se demostró entre el estatus pituitario e hipotalámico (r=0,61; p=<0,0001) y con la clasificación de Puget (r=0,31; p = 0,0382). CONCLUSIONES: Los craneofaringiomas predominaron en mujeres en su segunda década de vida, con síntomas cefalálgicos y trastornos visuales. Se localizaron generalmente en la región supraselar, con presencia de quistes, áreas de calcificación y realce tras la administración de contraste por técnicas imagenológicas de Tomografía Axial y Resonancia Magnética. La correlación más significativa se demostró entre el estatus pituitario con la clasificación de Puget y el hipotalámico

OBJECTIVES: To determine the correlation between the clinical evaluations of the pituitary and hypothalamic status with the imaging classifications of Kassam and Puget. MATERIAL AND METHODS: A study was carried out with a descriptive, correlational and retrospective design; with a convenience sample of a population (N = 1567) diagnosed with intracranial tumors by the Neurosurgery Service of the "Hermanos Ameijeiras" Hospital from January 2014 to December 2018. The variables age, sex, clinical manifestations, tumor location were included, hypothalamic status, pituitary status, imaging characteristics, hypothalamic involvement and relationship with the pituitary stem. PRINCIPAL RESULTS: The results were collected by a questionnaire; then it was compared by theoretical and statistical methods, systematizing the information using the InfoStat / L package for Windows. Forty-four cases were included, with a mean age of 32 ± 15.8 years, predominantly females (61.4%). The most common clinical manifestations were headache (88.6%) and visual disorders (77.2%), with lesions larger than 2 cm in diameter with suprasellar location (75.1%), hypothalamic status Grade II (45.5%) and Grade IV pituitary status (38.6%) all with enhanced contrast administration. The most significant association was demonstrated between pituitary and hypothalamic status (r = 0.61, p = <0.0001) and Puget classification (r = 0.31, p = 0.0382). CONCLUSIONS: The craniopharyngioma predominated in women in his second decade of life, with symptoms headache and visual disorders. The most common location at the region supraselar with presence of cysts, calcification and luster after the administration of contrast for techniques Computerized Axial Tomography and Nuclear Magnetic Resonance. The most significant correlation was demonstrated between the pituitary status with Puget's and the hipotalámico's classification

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

Hypothalamic hamartomas (HH) are rare, non-neoplastic heterotopic tissues which contains normal neurons and glia including oligodendrocytes and fibrillary astrocytes but in an abnormal distribution. They arise from the floor of the third ventricle, tuber cinereum, or mammillary bodies. Estimated incidence ranges from 1 in 50,000-1 in 1,000,000. Hypothalamic hamartomas are associated with different clinical presentations including various types of seizures, most characteristically; the gelastic seizures, precocious puberty, cognitive impairment, and behavioral changes. In this review, the authors discuss advancements in different diagnostic elements of hypothalamic hamartoma; including clinical features, EEG findings, and neuroimaging techniques. Moreover, different classifications described in the literature will be discussed.

Craniopharyngioma treatment: an updated summary of important clinicopathological concepts.

INTRODUCTION: Craniopharyngiomas (CPs) are benign histological tumors that may develop at different positions along the hypothalamic-pituitary axis. Their close, heterogenous relationship to the hypothalamus makes surgical removal challenging even though this remains the primary treatment strategy. AREAS COVERED: This article presents a critical overview of the pathological and clinical concepts regarding CPs that should be considered when planning treatment. Thus, we have performed a comprehensive review of detailed CP reports published between 1839 and 2020. EXPERT OPINION: CP surgery should pursue maximal tumor resection while minimizing the risk of injuring the hypothalamus. Therefore, surgical strategies should be individualized for each patient. Accurate assessment of presenting symptoms and preoperative MRI has proven useful to predict the type of CP-hypothalamus relationship that will be found during surgery. CPs with dense and extensive adhesions to the hypothalamus should be highly suspected when MRI shows the hypothalamus positioned around the mid-third of the tumor and an amputated upper portion of the pituitary stalk. Symptoms related to functional impairment of the infundibulo-tuberal area of the third ventricle floor, such as obesity/hyperphagia, Fröhlich's syndrome, diabetes insipidus, and/or somnolence, also indicate risky CP-hypothalamic adhesions. In these cases, limited tumor removal is strongly advocated followed by radiation therapy.

Diagnosis, Background, and Treatment of Hypothalamic Damage in Craniopharyngioma.

Craniopharyngiomas (CP) are rare brain tumors managed primarily with surgery and radiotherapy. There are 2 phenotypes of CP, i.e., one with a rather good outcome without hypothalamic damage and another with hypothalamic damage. With hypothalamic damage, progressive disease with recurrent operations and additional cranial radiotherapy often result in hypothalamic obesity, an affected psychosocial life, and cognitive dysfunction. The morbidity and mortality are increased for particularly cerebrovascular diseases. Preoperative hypothalamic involvement to predict hypothalamic damage is important for decision making for hypothalamus-sparing surgery. Also a postoperative hypothalamic damage evaluation with the use of hypothalamus volume measurement can predict hypothalamic obesity, which is important for early treatment options. The morbidity of CP includes cognitive dysfunction with attention deficits and impaired episodic memory and processing speed. Again patients with hypothalamic damage are more affected. Treatment options of hypothalamic obesity in the chronic phase are scarce and not convincingly successful. The most optimal situation is to try to hinder or stop the evolution of hypothalamic obesity. Prevention of hypothalamic damage is recommended, with special regard to hypothalamus-sparing therapeutic approaches that respect the integrity of essential nuclei located in both the medial and the posterior hypothalamic areas.

Pubertal timing predicts adult psychosexuality: Evidence from typically developing adults and adults with isolated GnRH deficiency.

Evidence suggests that psychosexuality in humans is modulated by both organizational effects of prenatal and peripubertal sex steroid hormones, and by activational effects of circulating hormones in adulthood. Experimental work in male rodents indicates that sensitivity to androgen-driven organization of sexual motivation decreases across the pubertal window, such that earlier puberty leads to greater sex-typicality. We test this hypothesis in typically developing men (n = 231) and women (n = 648), and in men (n = 72) and women (n = 32) with isolated GnRH deficiency (IGD), in whom the precise timing of peripubertal hormone exposure can be ascertained via the age at which hormone replacement therapy (HRT) was initiated. Psychosexuality was measured with the Sexual Desire Inventory-2 (SDI-2) and Sociosexual Orientation Inventory-Revised (SOI-R). In both sexes, earlier recalled absolute pubertal timing predicted higher psychosexuality in adulthood, although the magnitude of these associations varied with psychosexuality type and group (i.e., typically developing and IGD). Results were robust when controlling for circulating steroid hormones in typically developing participants. Age of initiation of HRT in men with IGD negatively predicted SOI-R. We discuss the clinical implications of our findings for conditions in which pubertal timing is medically altered.

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

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

Electrophysiological properties and seizure networks in hypothalamic hamartoma.

OBJECTIVE: Little is known about the intrinsic electrophysiological properties of hypothalamic hamartoma (HH) in vivo and seizure network since only few cases using stereoelectroencephalography (SEEG) electrodes exploring both cortex and HH have been published. To elucidate these issues, we analyzed simultaneous SEEG recordings in HH and cortex systematically. METHODS: We retrospectively investigated data from 15 consecutive patients with SEEG electrodes into the HH for the treatment purpose of radiofrequency thermocoagulation treatment. Additional SEEG electrodes were placed into the cortex in 11 patients to assess extra-HH involvement. Interictal discharges within the HH and anatomo-electroclinical correlations during seizures of each patient were qualitatively and quantitatively analyzed. RESULTS: Overall, 77 electrodes with 719 contacts were implanted, and 33 spontaneous seizures were recorded during long-term SEEG monitoring. Interictally, distinct electrophysiological patterns, including isolated intermittent spikes/sharp waves, burst spike and wave trains, paroxysmal fast discharges, periodic discharges, and high-frequency oscillations, were identified within the HH. Notably, synchronized or independent interictal discharges in the cortex were observed. Regarding the ictal discharges, the electrical onset pattern within the HH always started with abrupt giant shifts superimposed on low-voltage fast activity across patients. The gelastic seizure network mainly involved the HH, orbitofrontal areas, and cingulate gyrus. Seizures with automatisms and impaired awareness primarily propagated to mesial temporal lobes. Moreover, independent ictal discharges arising from the mesial temporal lobe were detected in three out of nine patients. INTERPRETATION: This study comprehensively reveals intrinsic electrophysiological patterns and epileptogenic networks in vivo, providing new insights into the mechanisms underlying cortical and subcortical epileptogenesis.

Discriminating hypothalamic oligomenorrhea/amenorrhea from hyperandrogenic oligomenorrhea/amenorrhea in exercising women.

The mechanism underlying oligo/amenorrhea in exercising women is often presumed as hypothalamic inhibition secondary to energy deficiency; however, hyperandrogenism may provide an alternative mechanism in some exercising women. Our purpose was to compare reproductive, metabolic, and androgen profiles of exercising women with eumenorrheic, ovulatory menstrual cycles (n = 91), oligo/amenorrhea without evidence of hyperandrogenism (Oligo/Amen; n = 83), and oligo/amenorrhea with evidence of hyperandrogenism (Oligo/Amen-HA; n = 17), and determine the prevalence of oligo/amenorrhea with evidence of hyperandrogenism in exercising women. Self-reported menstrual history and quantification of daily estrogen and progesterone urinary metabolites determined reproductive status. Resting energy expenditure, body composition, and metabolic hormone concentrations determined metabolic status. Serum androgens and calculated free androgen index (FAI) determined androgen status. Groups were similar in age (22.4 ± 0.3 years), height (165.1 ± 0.5 cm), resting energy expenditure (1198.4 ± 12.0 kcal/day), and total triiodothyronine (85.0 ± 1.5 ng/dL) concentration. Oligo/Amen-HA had greater weight (60.0 ± 1.6, 56.1 ± 0.7 kg), body mass index (22.3 ± 0.4, 20.6 ± 0.2 kg/m2), percentage body fat (27.3% ± 1.4%, 24.4% ± 0.6%), fat mass (16.2 ± 1.0, 13.8 ± 0.4 kg), insulin (5.8 ± 0.7, 4.2 ± 0.3 µIU/mL), leptin (12.2 ± 2.3, 6.6 ± 0.7 ng/mL), FAI (6.1 ± 0.3, 1.7 ± 0.1), and luteinizing hormone/follicle-stimulating hormone (1.9 ± 0.3, 1.3 ± 0.2) compared with Oligo/Amen, respectively. In our sample, 17% of those with oligo/amenorrhea had concurrent hyperandrogenism. This study supports that oligo/amenorrhea in some exercising women is related to hyperandrogenism. Novelty Caution must be utilized when discriminating hypothalamic oligo/amenorrhea from hyperandrogenic oligo/amenorrhea. In our sample, 17% of those with presumed hypothalamic oligo/amenorrhea had concurrent hyperandrogenism. Exercise and/or mild energy deficiency may be protective against developing severe hyperandrogenic symptoms.

Hypothalamic hamartomas in adulthood: Clinical spectrum and treatment outcome-A unicenter experience.

INTRODUCTION: Clinical manifestations of the hypothalamic hamartoma-epilepsy syndrome (HH-ES) in adulthood are variable. Efficacy of therapeutic options and outcome are diverse. METHODS: Retrospective study of adult patients diagnosed with a HH in magnetic resonance imaging and epilepsy who attended our tertiary Epilepsy Unit between 2003 and 2018. We report the clinical and electroencephalographic features of a series of adult patients with HH and related epilepsy seen in our center together with the treatments and seizure outcome. RESULTS: We describe a series of eight patients. Five males (62.5%), median age at evaluation was 28.5 years (IQR: 15.5). Clinical manifestations included focal with preserved and impaired awareness emotional seizures (gelastic seizures [GS]) in six patients (75%), focal tonic, atonic with impaired awareness and focal to bilateral tonic-clonic seizures. Mild GS were the only symptom in one patient. Three patients (37.5%) had endocrinological disturbances such as obesity and hypothyroidism. Fifty percent of the patients showed psychiatric comorbidity such as anxiety disorder and aggressiveness, and two patients had psychomotor delay. Seven patients (87.7%) had drug-resistant seizures and three of them were treated with radiosurgery. Out of the treated group, only one (33.3%) became seizure-free 2 years after surgery but developed psychiatric problems. The other two patients had an Engel IV outcome and received a vagal nerve stimulation (VNS) implant. VNS did not lead to changes either in intensity nor in seizure frequency. CONCLUSIONS: Hypothalamic hamartoma-epilepsy syndrome clinical manifestations in adult patients are as variable as at pediatric age. Outcome of therapeutic options such as radiosurgery or VNS may be poorer at this stage.

Advances in the management of craniopharyngioma in children and adults.

Background Childhood and adult-onset craniopharyngioma is a rare embryogenic tumor of the sellar, suprasellar, and parasellar region. Survival rates are high; however, tumor location and treatment sequalae including endocrine deficits, visual impairment, metabolic complications, cognitive and psychosocial deficits can significantly impair patient's quality of life. There is considerable controversy regarding the optimal management of craniopharyngiomas. Subtotal resection of the tumor followed by targeted irradiation to avoid further hypothalamic damage is currently indicated. Novel insights in the tumor's molecular pathology present the possibility for targeted therapy possibly decreasing the rate and severity of treatment-associated morbidity. Conclusions Craniopharyngioma should be seen as a chronic disease. To achieve optimal outcomes a multidisciplinary team of specialized neurosurgeons, neuro-radiologists, neuro-oncologists, pathologists and endocrinologists should be involved in the diagnosis, planning of the surgery, irradiation and long-term follow-up.

Opioids and reproduction.

More than 40years ago, the endogenous opioids were first described. Their role as important neuromodulators of pain and their influence on a variety of neuroendocrine control systems within the central nervous system has been recognized. More recently, endogenous opioids and their receptor have been identified in a variety of reproductive and non-reproductive tissues outside the central nervous system. What role the opioid system plays in these peripheral tissues and organs is not completely understood and thus the subjects of current research. In the central nervous system, endogenous opioids inhibit pulsatile Gonadotropin Releasing Hormone (GnRH) release, affecting the release of gonadotropins from the pituitary, and thus mediating stress response within the central nervous-pituitary-gonadal axes in both women and men-Peripherally, endogenous opioids have been demonstrated to be present-among other organs-in the pancreas and in the ovary, where they are produced by granulosa cells and may influence oocyte maturation. In men, endogenous opioids play a role in sperm production within the testis. Opioid antagonists such as naltrexone have been used to restore cyclicity in women through improvement in insulin resistance, GnRH-pulsatility and hyperandrogenemia stemming from specific pathophysiological conditions such as hypothalamic amenorrhea, polycystic ovarian syndrome, hyperinsulinemia, ovarian hyperstimulation syndrome. Opioid antagonists have also been used to treat male sexual disorders and male infertility. In summary, endogenous opioids exert a variety of actions within the reproductive system which are reviewed in this chapter.

Pathogenic variants of DYNC2H1, KIAA0556, and PTPN11 associated with hypothalamic hamartoma.

OBJECTIVE: Intensive genetic analysis was performed to reveal comprehensive molecular insights into hypothalamic hamartoma (HH). METHODS: Thirty-eight individuals with HH were investigated by whole exome sequencing, target capture-based deep sequencing, or single nucleotide polymorphism (SNP) array using DNA extracted from blood leukocytes or HH samples. RESULTS: We identified a germline variant of KIAA0556, which encodes a ciliary protein, and 2 somatic variants of PTPN11, which forms part of the RAS/mitogen-activated protein kinase (MAPK) pathway, as well as variants in known genes associated with HH. An SNP array identified (among 3 patients) one germline copy-neutral loss of heterozygosity (cnLOH) at 6p22.3-p21.31 and 2 somatic cnLOH; one at 11q12.2-q25 that included DYNC2H1, which encodes a ciliary motor protein, and the other at 17p13.3-p11.2. A germline heterozygous variant and an identical somatic variant of DYNC2H1 arising from cnLOH at 11q12.2-q25 were confirmed in one patient (whose HH tissue, therefore, contains biallelic variants of DYNC2H1). Furthermore, a combination of a germline and a somatic DYNC2H1 variant was detected in another patient. CONCLUSIONS: Overall, our cohort identified germline/somatic alterations in 34% (13/38) of patients with HH. Disruption of the Shh signaling pathway associated with cilia or the RAS/MAPK pathway may lead to the development of HH.

Investigating the Hypothesis of Stress System Dysregulation as a Risk Factor for Central Serous Chorioretinopathy: A Literature Mini-Review.

Background: This mini-review addressed the question "what do we know about the association between the dysregulation of stress systems (HPA axis and SAM) and the onset and prognosis of CSC in adult populations?" Methods: The literature mini-review was conducted through electronic searches using the PubMed, Web of Science, and Scopus databases. All published human and animal studies with both observational and experimental designs from 1966 to October 2018 were included. Results: Our search identified 229 reports, of which 32 articles were ultimately identified to be reviewed in this paper. Among these key articles, twenty-three were related to exogenous and/or endogenous high glucocorticoids as risk factors for CSC, seven were related to Type-A behavior and chronic psychological distress as risk factors for idiopathic CSC, and two were related to stress-induced animal models of CSC. Nineteen out of twenty-three studies in the first group reported a consistent association between high circulating corticosteroids and the onset and prognosis of CSC. Six out of seven studies in the second group reported a consistent association between stress-induced allostatic (over)load and the appearance of more- or less-severe CSC disorders, assuming that elevated circulating steroids may constitute a kind of risk factor for the eye through dysregulation of the HPA axis. All the selected studies reported HPA axis dysregulation as a possible common factor to explain the association between high circulating corticosteroids and CSC. In contrast, the involvement of the SAM system is only indirectly taken into consideration through the PA and HR measures and/or plasma and 24-h urinary catecholamine levels. Therefore, information regarding the involvement of SAM system dysregulation in the onset and prognosis of CSC is lacking. This observation is particularly relevant in view of the fact that animal models of CSC in monkeys are primarily induced by adrenergic hypertonia and that the course of experimental CSC is not further exacerbated by the administration of corticosteroids.

Pathophysiology and Individualized Treatment of Hypothalamic Obesity Following Craniopharyngioma and Other Suprasellar Tumors: A Systematic Review.

The development of hypothalamic obesity (HO) following craniopharyngioma (CP) and other suprasellar tumors leads to reduced patient quality of life. No treatment algorithms are currently available for management of HO. Depending on which hypothalamic nuclei are destroyed, the pathophysiologic mechanisms and clinical symptoms that contribute to HO differ among patients. Herein, we review the contribution of the hypothalamus to the pathophysiologic mechanisms and symptoms underlying CP-associated HO. Additionally, we performed a systematic search of MEDLINE and Embase to identify all intervention studies for weight management in patients with CP or other suprasellar tumors published until September 2017. The search yielded 1866 publications, of which 40 were included. Of these 40 studies, we identified four modalities for intervention (i.e., lifestyle, dietary, pharmacotherapeutic, or surgical) within six clinical domains (i.e., psychosocial disorders, hyperphagia, sleep disturbances, decreased energy expenditure, hyperinsulinemia, and hypopituitarism). We used the findings from our systematic review, in addition to current knowledge on the pathophysiology of HO, to develop an evidence-based treatment algorithm for patients with HO caused by CP or other suprasellar tumors. Although the individual effects of the HO interventions were modest, beneficial individual effects may be achieved when the pathophysiologic background and correct clinical domain are considered. These two aspects can be combined in an individualized treatment algorithm with a stepwise approach for each clinical domain. Recently elucidated targets for HO intervention were also explored to improve future management of HO for patients with CP and other suprasellar tumors.

[Evaluation of nutrition, body composition and features of dietetic counseling for patients with functional hypothalamic amenorrhea].

The assessment of nutrition status, anthropometry, eating disorders, fat tissue and leptin levels in 48 patients with functional hypothalamic amenorrhea (FHA) was conducted. The study of nutrition status revealed a discrepancy between the caloric intake and energy expenditure in 50% of patients, inadequate daily intake of carbohydrates in 91.7%, increased protein intake in 70.8% of patients. The recommended ratio of proteins, fats, carbohydrates in patients of the study group was not observed (1:1:0.3). It was noted that the deficit of adipose tissue and the decrease in serum leptin concentration were observed not only in patients with low body mass index), but also in 70% of women with normal values. Using the questionnaire Eating Disorder Inventory 2 (EDI-2) revealed that 54.2% of patients had drive for thinness and 22.9% of patients had body dissatisfaction. The results indicate the need for an integrated approach to the management of patients with FHA, which provides consultation of a gynecologist, psychotherapist and nutritionist.

Perioperative anesthetic management of children with congenital central hypoventilation syndrome and rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation undergoing thoracoscopic phrenic nerve-diaphragm pacemaker implantation.

BACKGROUND: Congenital Central Hypoventilation Syndrome and Rapid-Onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation are rare neurocristopathies characterized by autonomic dysregulation including bradyarrhythmias, abnormal temperature control, and most significantly, abnormal control of breathing leading to tracheostomy and ventilator dependence as life support. Surgical advancements have made phrenic nerve-diaphragm pacemakers available, to eliminate the tether to a mechanical ventilator for 12-15 hours each day. The thoracoscopic approach to implantation has allowed for a less invasive approach which may have implications for pain control and recovery time. However, thoracoscopic implantation of these devices presents several challenges to the anesthesiologist in these complex ventilator-dependent patients, including, but not limited to, sequential lung isolation, prevention of hypothermia, and management of arrhythmias. Postoperative challenges may also include strategies to treat hemodynamic instability, managing the ventilator following lung derecruitment, and providing adequate pain control. AIMS: We aimed to describe the anesthetic management of Congenital Central Hypoventilation Syndrome and Rapid-Onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation patients undergoing thoracoscopic phrenic nerve-diaphragm pacemaker implantation and the nature and incidence of perioperative complications. METHODS: A retrospective chart review was performed of 14 children with Congenital Central Hypoventilation Syndrome and Rapid-Onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation undergoing phrenic nerve-diaphragm pacemaker implantation at a single academic pediatric hospital between 2009 and 2017. Demographic information, intraoperative management, and perioperative complications were analyzed from patient records. RESULTS: Twelve of 14 patients (86%) underwent an inhalational induction via tracheostomy. Lung isolation was achieved via fiberoptic guidance of a single lumen endotracheal tube sequentially into the right or left mainstem bronchi for 12 patients (86%). Double lumen endotracheal tubes were utilized in two patients (7%) and bronchial blockers in two patients (7%) for lung isolation. Anesthesia was maintained using a balanced technique of volatile agents (sevoflurane/isoflurane) and opioids (fentanyl). Bradyarrhythmias developed in six patients (43%) during surgery, 5 (36%) responded to anticholinergics and one patient (7%) required backup cardiac pacing using a previously implanted bipolar cardiac pacemaker. Intraoperative hypothermia (<35.5°C) was present in five patients (36%) despite the use of warming devices. Hypercarbia (>50 mm Hg) during lung isolation was present in eight patients (57%) and hemoglobin desaturation (<90%) in four patients (29%). Postoperatively, oxygen desaturation was a common complication with nine patients (64%) requiring supplemental oxygen administration via mechanical ventilator or manual bag ventilation. Opioids via patient-controlled analgesia devices (12 patients, 86%) or intermittent injection (two patients, 14%) were administered to all patients for postoperative pain control. Phrenic nerve-diaphragm pacemaker placement was successful thoracoscopically in all patients with no perioperative mortality. CONCLUSION: The main anesthetic challenges in patients with Congenital Central Hypoventilation Syndrome and Rapid-Onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation include hemodynamic instability, the propensity to develop hypothermia, hypercarbia/hypoxemia, and the need to perform bilateral sequential lung isolation requisite to the thoracoscopic implantation technique. Most anesthetic agents can be used safely in these patients; however, adequate knowledge of the susceptibility to complications, coupled with adequate preparation and understanding of the innate disease characteristics, are necessary to treat anticipated complications.