Neuroendocrine changes in the hypothalamic-neurohypophysial system in the Wistar audiogenic rat (WAR) strain submitted to audiogenic kindling.

The Wistar audiogenic rat (WAR) strain is used as an animal model of epilepsy, which when submitted to acute acoustic stimulus presents tonic-clonic seizures, mainly dependent on brainstem (mesencephalic) structures. However, when WARs are exposed to chronic acoustic stimuli (audiogenic kindling-AK), they usually present tonic-clonic seizures, followed by limbic seizures, after recruitment of forebrain structures such as the cortex, hippocampus and amygdala. Although some studies have reported that hypothalamic-hypophysis function is also altered in WAR through modulating vasopressin (AVP) and oxytocin (OXT) secretion, the role of these neuropeptides in epilepsy still is controversial. We analyzed the impact of AK and consequent activation of mesencephalic neurocircuits and the recruitment of forebrain limbic (LiR) sites on the hypothalamic-neurohypophysial system and expression of Avpr1a and Oxtr in these structures. At the end of the AK protocol, nine out of 18 WARs presented LiR. Increases in both plasma vasopressin and oxytocin levels were observed in WAR when compared to Wistar rats. These results were correlated with an increase in the expressions of heteronuclear (hn) and messenger (m) RNA for Oxt in the paraventricular nucleus (PVN) in WARs submitted to AK that presented LiR. In the paraventricular nucleus, the hnAvp and mAvp expressions increased in WARs with and without LiR, respectively. There were no significant differences in Avp and Oxt expression in supraoptic nuclei (SON). Also, there was a reduction in the Avpr1a expression in the central nucleus of the amygdala and frontal lobe in the WAR strain. In the inferior colliculus, Avpr1a expression was lower in WARs after AK, especially those without LiR. Our results indicate that both AK and LiR in WARs lead to changes in the hypothalamic-neurohypophysial system and its receptors, providing a new molecular basis to better understaind epilepsy.

Diabetes insipidus.

Diabetes insipidus (DI) is a disorder characterized by excretion of large amounts of hypotonic urine. Central DI results from a deficiency of the hormone arginine vasopressin (AVP) in the pituitary gland or the hypothalamus, whereas nephrogenic DI results from resistance to AVP in the kidneys. Central and nephrogenic DI are usually acquired, but genetic causes must be evaluated, especially if symptoms occur in early childhood. Central or nephrogenic DI must be differentiated from primary polydipsia, which involves excessive intake of large amounts of water despite normal AVP secretion and action. Primary polydipsia is most common in psychiatric patients and health enthusiasts but the polydipsia in a small subgroup of patients seems to be due to an abnormally low thirst threshold, a condition termed dipsogenic DI. Distinguishing between the different types of DI can be challenging and is done either by a water deprivation test or by hypertonic saline stimulation together with copeptin (or AVP) measurement. Furthermore, a detailed medical history, physical examination and imaging studies are needed to ensure an accurate DI diagnosis. Treatment of DI or primary polydipsia depends on the underlying aetiology and differs in central DI, nephrogenic DI and primary polydipsia.

The Role of Neurohypophyseal Hormones Vasopressin and Oxytocin in Neuropsychiatric Disorders.

BACKGROUND AND OBJECTIVE: Although the neurohypophyseal hormones vasopressin (VP) and oxytocin (OT) are mostly known for their role respectively in antidiuresis, and in labour, lactation and maternal behavior, both might exert widespread influences either on emotion and cognition in healthy subjects, showing some gender-related differences. They interact with each other facilitating shifts between positive socially- oriented and defensive states. In fact, VP amplifies the reactivity to stressors showing also beneficial effects on attention, verbal learning as well as memory, whereas OT reduces the amplitude of the stress response, improves emotion processing, and can play a negative effect on memory and verbal learning in healthy individuals. Several data indicate the possible involvement of these neuropeptides in the pathophysiology of psychiatric conditions involving social interactions, such as autism, as well as in schizophrenia and depression. The aim of this paper is to review the literature relating to the role played by neurohypophyseal hormones in neuropsychiatric disorders. METHODS: We analyzed the best of published literature dealing with the relationships between neurohypophyseal hormones and neuropsychiatric conditions like autism (AD), major depressive disorder (MDD), bipolar disorder (BD) and schozophrenia, identifying keywords and MeSH terms in Pubmed and then searching them. The last search was performed on December 2017. RESULTS: Several studies indicate a role played by OT and VP in AD, schizophrenia, MDD and BD. Even if conflicting data have been reported, several mechanisms may be involved in these behavioral diseases, such as differences in aminoacid sequence and peptide biological activity, neurotransmission and genetic disorders involving OT and VP receptors. CONCLUSION: The involvment of VP and OT in neurpopsychiatric disorders can support a possible beneficial therapy with OT or with VP antagonists. The target may be obtained using effective drug delivery methods as well as the association with other drugs.

Hyponatremia with Loss of High Signal Intensity in the Posterior Pituitary Lobe on T1-weighted Magnetic Resonance Imaging.

Herein, we report on an 82-year-old woman who presented with anorexia. The patient had hyponatremia with preserved urinary osmotic pressure. T1-weighted magnetic resonance imaging (MRI) showed a lack of high signal intensity (SI) in the posterior pituitary lobe. Based on the patient's high levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP), heart failure was suspected. The heart failure may have caused arginine vasopressin (AVP) secretion. The depletion of AVP secretory granules may therefore cause the posterior pituitary gland to disappear on T1-weighted MRI.

Genetics of Diabetes Insipidus.

Diabetes insipidus is a disease characterized by polyuria and polydipsia due to inadequate release of arginine vasopressin from the posterior pituitary gland (neurohypophyseal diabetes insipidus) or due to arginine vasopressin insensitivity by the renal distal tubule, leading to a deficiency in tubular water reabsorption (nephrogenic diabetes insipidus). This article reviews the genetics of diabetes insipidus in the context of its diagnosis, clinical presentation, and therapy.

Vasopressin at Central Levels and Consequences of Dehydration.

Disorders of water balance are a common feature of clinical practice. An understanding of the physiology and pathophysiology of central vasopressin release and perception of thirst is the key to diagnosis and management of these disorders. Mammals are osmoregulators; they have evolved mechanisms that maintain extracellular fluid osmolality near a stable value, and, in animal studies, osmoregulatory neurons express a truncated delta-N variant of the transient receptor potential vannilloid (TRPV1) channel involved in hypertonicity and thermal perception while systemic hypotonicity might be perceived by TRPV4 channels. Recent cellular and optogenetic animal experiments demonstrate that, in addition to the multifactorial process of excretion, circumventricular organ sensors reacting to osmotic pressure and angiotensin II, subserve genesis of thirst, volume regulation and behavioral effects of thirst avoidance.

Microparticles generated by decompression stress cause central nervous system injury manifested as neurohypophysial terminal action potential broadening.

The study goal was to use membrane voltage changes during neurohypophysial action potential (AP) propagation as an index of nerve function to evaluate the role that circulating microparticles (MPs) play in causing central nervous system injury in response to decompression stress in a murine model. Mice studied 1 h following decompression from 790 kPa air pressure for 2 h exhibit a 45% broadening of the neurohypophysial AP. Broadening did not occur if mice were injected with the MP lytic agent polyethylene glycol telomere B immediately after decompression, were rendered thrombocytopenic, or were treated with an inhibitor of nitric oxide synthase-2 (iNOS) prior to decompression, or in knockout (KO) mice lacking myeloperoxidase or iNOS. If MPs were harvested from control (no decompression) mice and injected into naive mice, no AP broadening occurred, but AP broadening was observed with injections of equal numbers of MPs from either wild-type or iNOS KO mice subjected to decompression stress. Although not required for AP broadening, MPs from decompressed mice, but not control mice, exhibit NADPH oxidase activation. We conclude that inherent differences in MPs from decompressed mice, rather than elevated MPs numbers, mediate neurological injury and that a component of the perivascular response to MPs involves iNOS. Additional study is needed to determine the mechanism of AP broadening and also mechanisms for MP generation associated with exposure to elevated gas pressure.

Central diabetes insipidus: a previously unreported side effect of temozolomide.

CONTEXT: Temozolomide (TMZ) is an alkylating agent primarily used to treat tumors of the central nervous system. We describe 2 patients with apparent TMZ-induced central diabetes insipidus. Using our institution's Research Patient Database Registry, we identified 3 additional potential cases of TMZ-induced diabetes insipidus among a group of 1545 patients treated with TMZ. CASE PRESENTATIONS: A 53-year-old male with an oligoastrocytoma and a 38-year-old male with an oligodendroglioma each developed symptoms of polydipsia and polyuria approximately 2 months after the initiation of TMZ. Laboratory analyses demonstrated hypernatremia and urinary concentrating defects, consistent with the presence of diabetes insipidus, and the patients were successfully treated with desmopressin acetate. Desmopressin acetate was withdrawn after the discontinuation of TMZ, and diabetes insipidus did not recur. Magnetic resonance imaging of the pituitary and hypothalamus was unremarkable apart from the absence of a posterior pituitary bright spot in both of the cases. Anterior pituitary function tests were normal in both cases. Using the Research Patient Database Registry database, we identified the 2 index cases and 3 additional potential cases of diabetes insipidus for an estimated prevalence of 0.3% (5 cases of diabetes insipidus per 1545 patients prescribed TMZ). CONCLUSIONS: Central diabetes insipidus is a rare but reversible side effect of treatment with TMZ.

Central diabetes insipidus in an HHV6 encephalitis patient with a posterior pituitary lesion that developed after tandem cord blood transplantation.

A 60-year-old myelodysplastic syndrome patient underwent tandem cord blood transplantation. The primary cord blood graft was rejected, and human herpesvirus 6 (HHV6) encephalitis developed after engraftment of secondary cord blood. Polyuria and adipsic hypernatremia were observed during treatment of the encephalitis. The patient died of bacteremia caused by methicillin-resistant Streptococcus epidermis. HHV6 infection in the posterior pituitary was confirmed on autopsy, as was infection of the hippocampus, but not of the hypothalamus. This is the first case report of central diabetes insipidus caused by an HHV6 posterior pituitary infection demonstrated on a pathological examination.

Neurohypophyseal response to fluid resuscitation with hypertonic saline during septic shock in rats.

Septic shock is a serious condition with a consequent drop in blood pressure and inadequate tissue perfusion. Small-volume resuscitation with hypertonic saline (HS) has been proposed to restore physiological haemodynamics during haemorrhagic and endotoxic shock. In the present study, we sought to determine the effects produced by an HS infusion in rats subjected to caecal ligation and perforation (CLP). Male Wistar rats were randomly grouped and submitted to either CLP or sham surgery. Either HS (7.5% NaCl, 4 ml kg(-1) i.v.) or isotonic saline (IS; 0.9% NaCl, 4 ml kg(-1) i.v.) was administered 6 h after CLP. Recordings of mean arterial pressure and heart rate were made during this protocol. Moreover, measurements of electrolyte, vasopressin and oxytocin secretion were analysed after either the HS or the IS treatment. Six hours after CLP, we observed a characteristic decrease in mean arterial pressure that occurs after CLP. The HS infusion in these rats produced a transient elevation of the plasma sodium concentration and osmolality and increased plasma vasopressin and oxytocin levels. Moreover, the HS infusion could restore the mean arterial pressure after CLP, which was completely blunted by the previous injection of the vasopressin but not the oxytocin antagonist. The present study demonstrated that rats subjected to CLP and an infusion of hypertonic saline respond with secretion of neurohypophyseal hormones and a transient increase in blood pressure mediated by the V(1) receptor.

Differential diagnosis of infundibular dilation versus a small aneurysm of the internal carotid artery: assessment by three-dimensional rotational angiography with volume rendering.

We report our findings associated with the differential diagnosis of infundibular dilation (ID) versus a small intracranial aneurysm using three-dimensional rotational angiography with volume rendering (3DRA + VR). Angiographic findings associated with IDs found via two-dimensional digital subtraction angiography (2D-DSA) or 3DRA + VR were reviewed for 138 consecutive patients with known or suspected aneurysms. Two readers independently evaluated the results of 2D-DSA and 3DRA + VR according to the same diagnostic criteria. We also evaluated the ability of 3D-DSA to show the spatial relation between IDs and anterior choroidal (AchA)/posterior communicating (PcomA) arteries. 2D-DSA and 3DRA + VR found 41 and 48 IDs, respectively. 2D-DSA missed five AchA and two PcomA IDs. 2D-DSA was significantly inferior to 3DRA + VR for displaying the spatial relation between IDs and AchA/PcomA (P = 0). Thus, 3DRA + VR provides more useful information for distinguishing IDs from aneurysms. The superiority of 3DRA + VR might be because of its ability to display the spatial relation between IDs and AchA/PcomA.

Effects of sodium diclofenac on the concentration function in animals with different neurohypophyseal status.

The characteristics of the osmotic concentration system under conditions of sodium diclofenac treatment were studied in Wistar rats with normally functioning vasopressin gene and homozygotic Brattleboro rats completely lacking endogenous vasopressin. Blockade of prostaglandin synthesis in rats with different neurohypophyseal status stimulated urinary osmolality to a different degree. Different contribution of sodium cations and urea to osmotic concentration was revealed.

Infundíbulo-neurohipofisitis: evolución a 10 años de un caso en la edad pediátrica / Infundibulo-hypophysitis in a girl: 10 years follow-up

No disponible

Infundibulo-tuberal or not strictly intraventricular craniopharyngioma: evidence for a major topographical category.

PURPOSE: This study investigates retrospectively the clinical, neuroradiological, pathological and surgical evidence verifying the infundibulo-tuberal topography for craniopharyngiomas (CPs). Infundibulo-tuberal CPs represent a surgical challenge due to their close anatomical relationships with the hypothalamus. An accurate definition of this topographical category is essential in order to prevent any undue injury to vital diencephalic centres. METHODS: A systematic review of all scientific reports involving pathological, neuroradiological or surgical descriptions of either well-described individual cases or large series of CPs published in official journals and text books from 1892 to 2011 was carried out. A total of 1,232 documents providing pathological, surgical and/or neuroradiological evidence for the infundibulo-tuberal or hypothalamic location of CPs were finally analysed in this study. FINDINGS: For a total of 3,571 CPs included in 67 pathological, surgical or neuroradiological series, 1,494 CPs (42%) were classified as infundibulo-tuberal lesions. This topography was proved in the autopsy of 122 non-operated cases. The crucial morphological finding characterizing the tubero-infundibular topography was the replacement of the third ventricle floor by a lesion with a predominant intraventricular growth. This type of CP usually presents a circumferential band of tight adherence to the third ventricle floor remnants, formed by a functionless layer of rective gliosis of a variable thickness. After complete surgical removal of an infundibulo-tuberal CP, a wide defect or breach at the floor of the third ventricle is regularly observed both in the surgical field and on postoperative magnetic resonance imaging studies. CONCLUSIONS: Infundibulo-tuberal CPs represent a major topographical category of lesions with a primary subpial development at the floor of the third ventricle. These lesions expand within the hypothalamus itself and subsequently occupy the third ventricle; consequently, they can be classified as not strictly intraventricular CPs. A tight attachment to the hypothalamus and remnants of the third ventricle floor is the pathological landmark of infundibulo-tuberal CPs.

Manejo y tratamiento microquirúrgico de las dilataciones infundibulares de la arteria comunicante posterior. Serie de nueve casos y revisión de la literatura / Management and microsurgical treatment of infun-dibular dilatations of the posterior communicating artery. Series of nine cases and review of the literature

Introducción. La dilatación infundibular (DI) de la arteria comunicante posterior (AComP) se define como la dilatación cónica, triangular o en forma de embudo, menor de 3 mm, en el origen de la AComP de la arte­ria carótida interna. El propósito del presente trabajo es presentar la experiencia propia en el tratamiento microquirúrgico de la DI de la AComP, revisar la biblio­grafía y proponer algoritmos para optimizar su manejo clínico y microquirúrgico. Material y métodos. Se han estudiado nueve casos de DI intervenidos a través de un abordaje pterional. En cuatro pacientes con hemorragia subaracnoidea (HSA) la DI se consideró la única causa del sangrado; en otros cuatro pacientes la DI se intervino tras una HSA por ruptura de otra lesión aneurismática; finalmente, en un paciente con pseudoxantoma elástico la DI se intervino de forma preventiva. Resultados. En ocho casos se procedió al clipaje de la DI y cierre de la AComP y en uno al reforzamiento de la DI al tratarse de una AComP del tipo fetal. No aparecie­ron complicaciones salvo una paresia transitoria del III par. El Glasgow Outcome Scale al alta y al año fue de 5 en todos los casos. Conclusiones. La DI de la AComP es una lesión de significado no aclarado, pero que plantea la necesidad de considerar su tratamiento en algunas ocasiones: 1. En pacientes con aneurismas rotos sometidos a cirugía y DI homolateral se recomienda explorar y tratar la lesión; (..) (AU)

Introduction. The infundibular dilatation (ID) of the posterior communicating (PCom) artery is defined as the conic, triangular or infundibular shaped, less than 3mm wide, origin of the PCom artery from the internal carotid artery. The purpose of this paper is to present the personal experience in the microsurgical manage­ment of the ID, to review the literature and to propose some algorithms to improve its clinical and microsurgi­cal management. Material and methods. Nine cases of ID have been operated on through a pterional approach. In four patients with subarachnoid hemorrhage (SAH) the ID was considered as the potential source of the bleeding; in four cases the ID was treated after a SAH due to the rupture of an aneurysm; finally, an ID was treated in patient with diagnosis of pseudoxantoma elasticum. Results. In eight cases the ID was clipped and the Pcom artery subsequently occluded and in the remai­ning case the ID was associated with a fetal PComA and the ID was reinforced. There were no complications excepting a transitory third cranial nerve paresis. The Glasgow Outcome Scale was 5 in all cases at discharge and one year later. Conclusions. The true significance of the ID remains unknown, but in some instances it is necessary to con­sider its management: 1. In patients with ruptured aneurysms submited to microsurgical clipping and with an ipsilateral ID, the lesion must be explored and treated; 2. In patients with ruptured aneurysms treated with endovascular procedures or harbouring an ID contralateral to a microsurgically treated aneurysm, the microsurgical indication will be done after conside­ring all risk factors; 3. In patients with SAH and an ID as the only potential source of the bleeding there would be an indication for microsurgical exploration; 4. The incidental finding of an ID should be indication for (..) (AU)

Posterior pituitary (PP) evaluation in patients with anterior pituitary defect associated with ectopic PP and septo-optic dysplasia.

OBJECTIVE: Controversies exist about posterior pituitary (PP) function in subjects with ectopic PP (EPP) and with cerebral midline defects and/or their co-occurrence. We investigate water and electrolyte disturbances in patients at risk for PP dysfunction. DESIGN: The study was conducted in a single Pediatric Endocrinology Research Unit. METHODS: Forty-two subjects with childhood-onset GH deficiency were subdivided into five groups: normal magnetic resonance imaging (n=8, group 1); EPP (n=15, group 2); septo-optic dysplasia (SOD) with normal PP (n=4, group 3); EPP and SOD without (n=7, group 4), and with additional midline brain abnormalities (n=8, group 5). At a mean age of 16.0±1.1 years, they underwent a 120 min i.v. infusion with hypertonic 5% saline and evaluation of plasma osmolality (Posm), arginine vasopressin (AVP), thirst score (in groups 1 and 2), and urinary osmolality were performed. RESULTS: Mean Posm and AVP significantly increased from baseline scores (284.7±4.9 mosm/kg and 0.6±0.2 pmol/l) to 120 min after saline infusion (300.5±8.0 mosm/kg and 10.3±3.3 pmol/l, P<0.0001). Group 5 showed higher mean Posm and lower mean AVP at all time points (P<0.0001). Mean thirst score did not show a significantly different trend between the groups 1 and 2. Urine osmolality was above 750 mosm/kg in all but seven patients after osmotic challenge. CONCLUSIONS: Patients with midline brain abnormalities and EPP have defective osmoregulated AVP. Patients with EPP and congenital hypopituitarism have normal PP function.

Isolated impairment of posterior pituitary function secondary to severe postpartum haemorrhage due to uterine rupture.

Cranial diabetes insipidus (DI) due to postpartum haemorrhage is an extremely rare clinical event. We describe herein isolated posterior pituitary insufficiency in a 26-year-old woman who had undergone subtotal hysterectomy for severe postpartum haemorrhage because of uterine rupture. The patient experienced polyuria within 6 h postoperatively. DI was suggested by the elevated urine volumes and low urine specific gravity. The diagnosis of DI was confirmed by water deprivation test and vasopressin stimulation test. The anterior pituitary function was within normal limits. A high clinical suspicion is certainly required for the diagnosis of DI in the immediate postpartum period. To rapidly initiate appropriate therapy, the possibility of DI should always be kept in mind while evaluating patients who have polyuria and polydipsia after severe postpartum bleeding. Delay or failure to treat this condition might result in hypovolemic shock.

Neurohypophyseal dysfunction during septic shock.

Septic shock is characterized by vasodilation and hypotension despite increased vasoconstrictors. While nitric oxide is known to be responsible for vasodilation, failure of vascular smooth muscle to constrict may be due in part to low plasma levels of vasopressin, a neurohypophyseal hormone. In the initial phase of septic shock, vasopressin concentration usually increases but then decreases to a significantly lower concentration after onset of septic shock. In this review, we discuss the neural mechanisms for the regulation of vasopressin secretion during septic shock.