Reduced Numbers of Corticotropin-Releasing Hormone Neurons in Narcolepsy Type 1.

Narcolepsy type 1 (NT1) is a chronic sleep disorder correlated with loss of hypocretin(orexin). In NT1 post-mortem brains, we observed 88% reduction in corticotropin-releasing hormone (CRH)-positive neurons in the paraventricular nucleus (PVN) and significantly less CRH-positive fibers in the median eminence, whereas CRH-neurons in the locus coeruleus and thalamus, and other PVN neuronal populations were spared: that is, vasopressin, oxytocin, tyrosine hydroxylase, and thyrotropin releasing hormone-expressing neurons. Other hypothalamic cell groups, that is, the suprachiasmatic, ventrolateral preoptic, infundibular, and supraoptic nuclei and nucleus basalis of Meynert, were unaffected. The surprising selective decrease in CRH-neurons provide novel targets for diagnostics and therapeutic interventions. ANN NEUROL 2022;91:282-288.

The Missing Link: A Case of Absent Pituitary Infundibulum and Ectopic Neurohypophysis in a Pediatric Patient with Heterotaxy Syndrome.

We report a case of absent pituitary infundibulum and ectopic neurohypophysis in a 4-year-old patient presenting clinically with hypopituitarism as well as heterotaxy syndrome complicated by global developmental delay and growth retardation. The clinical and laboratory workup of our patient suggested underlying hypopituitarism related to either congenital or acquired pathology, necessitating MRI to distinguish between them. We explain the various structural causes of hypopituitarism and detail how to predict the MRI findings and treatment, based on a fundamental understanding of the anatomy and pathophysiology of the hypothalamic pituitary axis and distinguishing anterior versus posterior pituitary hormone derangements. We also discuss two important theories widely acknowledged in the literature to explain congenital hypopituitarism: 1. Head trauma typically during birth resulting in a stretch injury to the infundibulum. 2. Congenital fetal maldevelopment of midline structures.

Expanding the spectrum of human ganglionic eminence region anomalies on fetal magnetic resonance imaging.

INTRODUCTION: Ganglionic eminence (GE) is a transient fetal brain structure that harvests a significant amount of precursors of cortical GABA-ergic interneurons. Prenatal magnetic resonance (MR) imaging features of GE anomalies (i.e., cavitations) have already been reported associated with severe micro-lissencephaly. The purpose of this report was to illustrate the MR imaging features of GE anomalies in conditions other than severe micro-lissencephalies. METHODS: Among all the fetuses submitted to prenatal MR imaging at our center from 2005 to 2014, we collected eight cases with GE anomalies and only limited associated brain anomalies. The median gestational age at the time of MR imaging was 21 weeks ranging from 19 to 29 weeks. Two senior pediatric neuroradiologists categorized the anomalies of the GE region in two groups: group one showing cavitation in the GE region and group two showing enlarged GE region. For each fetal case, associated cranial anomalies were also reported. RESULTS: Five out of the eight cases were included in group one and three in group two. Besides the GE region abnormality, all eight cases had additional intracranial anomalies, such as mild partial callosal agenesis, vermian hypoplasia and rotation, cerebellar hypoplasia, ventriculomegaly, enlarged subarachnoid spaces, molar tooth malformation. Ultrasound generally detected most of the associated intracranial anomalies, prompting the MR investigation; on the contrary in none of the cases, GE anomalies had been detected by ultrasound. CONCLUSIONS: Our observation expands the spectrum of human GE anomalies, demonstrating that these may take place also without associated severe micro-lissencephalies.

Ganglionic eminence within the early developing brain visualized by 3D transvaginal ultrasound.

AIM: Early diagnosis of cerebral congenital anomalies requires a profound knowledge of the anatomy of the developing human brain. The ganglionic eminences (GE) are crucial structures of the brain, giving rise mostly to the basal nuclei. The aim of this explorative study is to assess the GE within the embryonic and early fetal brain by using 3D transvaginal US. MATERIAL AND METHODS: From March 2015 to May 2015, a total of 18 singleton non-malformed embryos and fetuses at 9-13 weeks of gestation were assesed in vivo by transvaginal ultrasound using a Voluson E10, BT 15 scanner (GE Healthcare, Zipf, Austria). The 3D sonography was performed routinely as the subjects were scanned. Inter-observer agreement (concordance) was calculated using the Cohen's kappa statistics. RESULTS: At 9 gestational weeks, no GE was identified. At 10 gestational weeks the GE were identified as mere thickenings in the lateral wall of the cerebral hemispheres, well depicted by 3D transvaginal ultrasound using the HDlive rendering mode and the OmniView® software. Starting with 11 gestational weeks the GE are evident. The results of inter-observer agreement for ganglionic eminences identification were as follows: observed agreement Po=0.94, expected agreement Pe=0.76, kappa coefficient=0.83, which means a very good agreement between the observers. CONCLUSIONS: The GE can be clearly visualized by 3D transvaginal sonography, and especially by HDlive rendering mode. This method has become the "golden standard" for in vivo morphological studies of the embryonic and early fetal brain.

Impaired somatostatin accumulation within the median eminence in mice with mosaic mutation.

OBJECTIVES: The mosaic mutation (Atp7a(mo-ms)) linked to X-chromosome is caused by changes in the Atp7a gene encoding CPx-type protein responsible for the ATP-dependent copper transport across cell membranes. Mosaic mutant males represent an animal model for Menkes disease in humans. Starting from the eighth day of life the mosaic males exhibit a progressive decrease in body weight with poor viability and progressive paresis of the hind limbs. In order to examine whether hypothalamic somatostatin metabolism may be different in normal and copper deficient mice, somatostatin accumulation at the level of median eminence in 14 days old normal and mosaic mutant males was compared. METHODS: An electron microscopic immunocytochemical study on ultrathin brain slices was performed according to post-embedding immunogold procedure. RESULTS: In non-mutant animals somatostatin has been detected in many synapses within median eminence. Gold particles moderately decorated synaptic vesicles and mitochondria. In mosaic mutant animals somatostatin expression within the median eminence was very low and only a few gold particles represented somatostatin. Particles were sporadically associated with synaptic vesicles, mitochondria or cytoskeleton elements. Moreover, pre- and post- synaptic parts of synapses were very often swollen. CONCLUSION: Our data demonstrating that copper deficiency leads to the pathological changes within the median eminence ultrastructure and severe impairment of somatostatin expression suggest that this trace metal is an important element necessary for normal neurohormonal brain development.

Serial long-term assessment of in vivo LHRH release from a discrete area of the ewe median eminence using multiple guide cannula assembly and removable push-pull cannulae.

Analysis of neuronal interactions at the median eminence (ME) that control anterior pituitary function requires sampling of in vivo release of specific hypophysiotropic components and of putative inputs that might regulate such a release. We developed a multiple guide cannula assembly (MGCA) to sample repetitively discrete areas of the ewe ME, using removable push-pull cannula (PPC) probes. The MGCA is attached to the skull over the ME using stereotaxic surgery. A specific guide cannula of the assembly (1 of 48 guides) located on the midline and directly on top of the central portion of the ME is selected based on roentgenograms obtained after infusion of radiopaque contrast material into the third ventricle. The MGCA and the large size of the ewe brain allows the simultaneous positioning of a PPC probe, an infusion cannula or another removable probe in additional discrete hypothalamic and extrahypothalamic areas. To determine the capabilities of this sampling technique, we assessed in vivo release of LHRH from the extracellular space at the posterior-lateral ME, under various reproductive conditions that have well-defined LH-secretory patterns. The pulsatile profile of both LHRH and LH was significantly lower in anestrus than during the follicular phase of cycling ewes. In vivo pulsatile release of LHRH was higher in the follicular than in the midluteal phase of ewes sampled repetitively from the same ME site during three consecutive estrous cycles. All ewes showed increased midluteal progesterone levels. In vivo LHRH release, as determined by PPC sampling of the extracellular fluid at the posterior-lateral ME, probably reflects a mix of hypophysiotropic and nonhypophysiotropic LHRH components. Histological analysis revealed a well-organized, pallisade-like array of astroglial processes along the track of chronically implanted cannulae. This glial scar is disrupted along the tracks of acutely reimplanted cannulae but without apparent difference in the yield of the method. Our method increases the efficiency and versatility of ME PPC sampling providing an additional tool to assess the role of the ME as the final neuroendocrine control site of anterior pituitary function.