Treatment strategies for inverted papillomas with intracranial or intraorbital involvement.

OBJECTIVE: Sinonasal inverted papillomas are challenging benign tumours of the nasal cavity because of their high recurrence rates and the lifetime malignant transformation risk of 10 per cent as well as their locally aggressive behaviour. This study aimed to describe treatment strategies for inverted papillomas with intracranial or intraorbital involvement. METHOD: This was a prospective case series study of 18 patients with inverted papilloma with intracranial or intraorbital involvement. Patient demographic data, imaging, pathology, surgical technique and recurrences were recorded prospectively over a period of seven years. RESULTS: A total of 83 per cent of the patients in this study had been previously operated on, consisting of 8 cases with intracranial involvement, 1 case with intraorbital involvement and 9 with both. During follow up with a medium of 37 months (range, 13-115 months) there were two recurrences. CONCLUSION: It was postulated that intracranial or intraorbital involvement observed in this series was the result of multiple revisions. However, using accurate imaging protocols and the pedicle-oriented approach for tumour excision, complete tumour removal was achieved in most cases with minimal post-operative complications.

A systematic classification of the left-sided aortic arch variants based on cadaveric studies' prevalence.

INTRODUCTION: Typical branching pattern of the left-sided aortic arch consists of the brachiocephalic trunk (BCT), the left common carotid artery (LCCA) and the left subclavian artery (LSA). Variant patterns have been associated with a broad spectrum of pathologies. The meticulous knowledge of potential aortic arch variants is of utmost importance to radiologists, interventional cardiologists, vascular and thoracic surgeons. The current systematic review collects all aortic arch branching patterns and their frequency as published by various cadaveric studies, calculates prevalence taking into account the gender and the different people background, as well. All extracted variant patterns are classified into types and subtypes according to the number of emerging (major and minor) branches (1, 2, 3, 4 and 5) and to the prevalence they appear. In cases of similar prevalence, total cases were taken into consideration; otherwise the variants were classified under the title "other rare variants". METHODS: A systematic online search of PubMed and Google books databases was performed only in cadaveric studies. RESULTS: Twenty studies with typical (78% prevalence) and variable (22%) branching patterns were included. Types 3b, 2b, 4b, 1b and 5b had a prevalence of 81%, of 13%, of 5%, 0% and of 0%, respectively. Common variants were the brachiocephalico-carotid trunk (BCCT, 49% prevalence), the aberrant left vertebral artery (LVA, 41%) and the aberrant right subclavian artery (ARSA, 8%). LVA of aortic origin was detected in 32%, the bicarotid trunk (biCT) in 5% and the bi-BCT trunk in 3%. Thyroidea ima artery, a minor branch emerging from the aortic arch was found in 2%. Coexisted variants were detected in 4% (ARSA with a distinct RCCA and LCCA origin), in 3% (BCCT with a LVA of aortic origin), in 2% (ARSA with a biCT and a vertebrosubclavian trunk). CONCLUSION: No significant gender or ethnic differences exist among the 5 branching types. The proposed classification scheme aims to become a valuable and easy to use tool in the hands of all physicians involved in diagnosis and treatment of aortic arch pathology. It could be also useful in anatomical education, as well.

Higher Orexin A levels in lumbar compared to ventricular CSF: a study in idiopathic normal pressure hydrocephalus.

Orexin A (ORX-A) is implicated in the regulation of various physiological processes, including sleep/wake cycles and reward/motivation. The hypothalamic ORX-A neurons project throughout the brain and spinal cord. In the present study we established and compared ORX-A levels in lumbar and ventricular cerebrospinal fluid (CSF) samples, drawn from idiopathic normal pressure hydrocephalus (INPH) patients, during respectively, lumbar puncture and shunt placement. Ventricular and lumbar CSF levels of total protein and of the dopamine, serotonin and norepinephrine metabolites HVA, 5-HIAA and MHPG respectively, were also estimated. ORX-A was quantified using a commercially available radioimmunoassay kit. Neurotransmitter metabolites were quantified by high performance liquid chromatography. Expectedly, HVA and 5-HIAA levels were significantly higher and total protein levels lower in ventricular compared to lumbar CSF while there were no differences in MHPG levels. However, in contrast to HVA and 5-HIAA and similar to total protein, lumbar ORX-A levels were significantly higher than ventricular levels. The higher lumbar compared to ventricular ORX-A levels may reflect elevated contributions from the spinal cord. The finding of a ventriculo-lumbar difference for ORX-A should be considered in studies utilizing its CSF levels in assessing Orexin system status.

Twelve-year hospital outcomes in patients with idiopathic hydrocephalus.

OBJECTIVE: The aim of this study was to examine patients who were admitted for the first-ever shunting for idiopathic normal pressure hydrocephalus (INPH) during a 12-year period, in terms of variation rate, patient demographic characteristics, shunt procedures, postoperative complications, and hospital outcome. METHODS: An electronic database which included all shunted patients (1998 to 2009) was used to retrieve demographic, clinical, and hospital outcome data. INPH patient identification was based on clinical and imaging diagnostic criteria. RESULTS: INPH patients (n = 238) who had undergone shunting were identified. The mean age and male to female ratio of INPH patients were 73.3 (± 7) years and 1.28:1, respectively.The number of surgically managed INPH cases and proportion of INPH-related shunting procedures rose consecutively during the second and last third of the study period. Ventriculoperitoneal shunts (n = 129; 54.2%) were the most commonly used configurations, followed by ventriculoatrial (n = 108; 45.4%) and lumboperitoneal (n = 1; 0.4%). Intrahospital shunt-related complications were hematomas (0.84%), meningitis (0.42%), and status epilepticus (0.42%). A favorable outcome was reported for 66.8% of patients; 31.5% showed no change. Overall inpatient mortality was 1.7%. CONCLUSION: The quantitative findings indicate a progressive rise in the number of surgically managed INPH patients that parallels a rise in the proportion of INPH-related shunting procedures. Contributing factors are likely to include improved diagnosis and an increase in awareness of the INPH syndrome by referring physicians.

Serum levels of S-100B after recreational scuba diving.

Recreational scuba diving is a sport of increasing popularity. Previous studies indicating subtle brain injury in asymptomatic divers imply a cumulative effect of minor neural insults in association with diving for professional and/or recreational purposes, over the long-term. This is the first study to investigate putative neural tissue burden during recreational scuba diving by measuring circulating levels of S-100B, a sensitive biomarker of brain injury. 5 male divers performed 3 consecutive dives under conservative recreational diving settings (maximum depth 15 m, duration of dive 56 min, ascend rate 1.15 m/min) with an interval of 12 h between each session. Although a small increase in serum S-100B levels after each dive was apparent, this increase did not quite reach statistical significance (p=0.057). Moreover, no abnormal S-100B values were recorded (mean baseline: 0.06 µg/L, mean post-dive: 0.086 µg/L) and no effect of the 3 consecutive dives on changes in S-100B levels was detected. These results suggest that under the experimental conditions tested, diving does not seem to have a discernible and/or cumulative impact on central nervous system integrity. The extent to which variable diving settings and practices as well as individual susceptibility factors underlie putative neural tissue burden in asymptomatic divers, remains to be established.

Evidence for suprachiasmatic vasopressin neurones innervating kisspeptin neurones in the rostral periventricular area of the mouse brain: regulation by oestrogen.

In rodents, a circadian signal from the suprachiasmatic nucleus (SCN) is essential for the pro-oestrous surge of gonadotrophin-releasing hormone (GnRH), which, in turn, induces luteinising hormone (LH) surge and ovulation. We hypothesised that kisspeptin (KP) neurones in the anteroventral periventricular and periventricular preoptic nuclei (AVPV/PeN) form part of the communication pathway between the SCN and GnRH neurones. In anterograde track tracing studies, we first identified vasopressin (VP)-containing axons of SCN origin in apposition to KP-immunoreactive (IR) neurones. Studies to quantify this input relied on the observation that VP-synthesising neurones in the SCN differ from other VP systems in their lack of galanin expression. In ovariectomised mice, 30.79 +/- 1.63% of KP-IR perikarya and proximal dendrites within the AVPV/PeN received galanin-negative VP-IR varicosities. Oestrogen-treatment significantly increased the number of KP-IR neurones, with their percentage apposed by galanin-negative VP-IR varicosities (46.95 +/- 1.88%) and the number of VP-IR appositions on individual KP-IR neurones. At the ultrastructural level, the VP-IR terminals formed symmetric synapses with KP-IR neurones, which was in accordance with the morphology of inhibitory synapses established by SCN neurones. By contrast to VP, vasoactive intestinal polypeptide (VIP), which is synthesised by a distinct subset of SCN neurones, occurred only rarely in axons apposed to KP-IR neurones. Altogether, our results are consistent with the hypothesis that KP neurones located in the mouse AVPV/PeN receive circadian information from the SCN via a vasopressinergic monosynaptic pathway, which is enhanced by oestrogen.

Oestrogen receptor alpha and beta immunoreactive cells in the suprachiasmatic nucleus of mice: distribution, sex differences and regulation by gonadal hormones.

Oestrogen regulates various aspects of circadian rhythm physiology. The presence of oestrogen receptors within the suprachiasmatic nucleus (SCN), the principal circadian oscillator, indicates that some actions of oestrogen on circadian functions may be exerted at that site. The present study analysed sex differences, topographic distribution, and neurochemical phenotype of neurones expressing the alpha and beta subtypes of oestrogen receptors (ERalpha and ERbeta) in the mouse SCN. We found that relatively few neurones in the SCN are immunoreactive (IR) for ERalpha (approximately 4.5% in females and 3% in males), but five- to six-fold more SCN neurones express ERbeta. ER-IR neurones are primarily in the shell subdivision of the nucleus and show differences between the sexes, significantly greater numbers being found in females. Treatment of male or female gonadectomised mice with oestradiol benzoate for 24 h substantially reduced the number of ERbeta-IR neurones, but not ERalpha-IR neurones. Double-labelling immunocytochemical experiments to characterise the phenotype of the oestrogen-receptive neurones showed the presence of the calcium-binding proteins calretinin or calbindin D28K in approximately 12% and 10%, respectively, of ERalpha-IR neurones. A higher proportion (approximately 38%) of ERbeta-IR neurones contains calbindin D28K; a few (approximately 2%) express calretinin or vasopressin. These double-labelled cells appear primarily in the shell subdivision of the SCN. Neither vasoactive intestinal polypeptide- nor gastrin releasing peptide-immunoreactivity was observed in ER-IR neurones. These data indicate that the primary target cells for oestrogen are in the shell subdivision of the nucleus. The sexually differentiated expression and distribution of ERalpha and ERbeta in various cell populations of the SCN suggest multiple modes of oestrogen signalling within this nucleus, which may modulate circadian functions.

Fasting reduces KiSS-1 expression in the anteroventral periventricular nucleus (AVPV): effects of fasting on the expression of KiSS-1 and neuropeptide Y in the AVPV or arcuate nucleus of female rats.

Changes in metabolic state, such as those induced by fasting, have profound effects on reproduction. In rats, the time-course over which fasting inhibits luteinising hormone (LH) release is reduced to 48 h by the presence of oestradiol-17beta (E(2)). Hypothalamic kisspeptin plays a key role in mediating the actions of E(2) on gonadotrophin-releasing hormone (GnRH) neurones, and thereby promotes LH release. KiSS-1-expressing neurones are found in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). Extensive evidence implicates the AVPV in GnRH release and the ARC in energy balance. The latter nucleus also contains neurones that express neuropeptide Y (NPY), an orexigenic peptide implicated in GnRH control. To elucidate the involvement of kisspeptin and/or NPY in hypothalamic responses to fasting, their expression was quantified by in situ hybridisation histochemistry in ovariectomised rats, with or without E(2) replacement, before and after 48 h of fasting. In the presence of E(2), but not in its absence, the fasting suppressed plasma LH. In the AVPV, the low level of KiSS-1 expression found in the absence of E(2) was unaffected by fasting. By contrast, the elevated level found in the presence of E(2) was suppressed by fasting. Independent of E(2), fasting had no effect on KiSS-1 expression in the ARC, but increased NPY expression at that site. The present study has identified the AVPV as a site at which KiSS-1 expression can be influenced by fasting. The results suggest that inhibition of KiSS-1 expression in the AVPV may be a significant factor in restraining the gonadotrophic axis in response to negative energy balance in the presence of oestrogen. The extent to which the concurrent rise in NPY expression in the ARC may contribute to the suppression of LH release by influencing AVPV kisspeptin neurones, directly or indirectly, or by actions independent of kisspeptin, remains to be established.

Characterization of gonadotrophin-releasing hormone precursor cDNA in the Old World mole-rat Cryptomys hottentotus pretoriae: high degree of identity with the New World guinea pig sequence.

Regulation of pituitary gonadotrophins by the decapeptide gonadotrophin-releasing hormone 1 (GnRH1) is crucial for the development and maintenance of reproductive functions. A common amino acid sequence for this decapeptide, designated as 'mammalian' GnRH, has been identified in all mammals thus far investigated with the exception of the guinea pig, in which there are two amino acid substitutions. Among hystricognath rodents, the members of the family Bathyergidae regulate reproduction in response to diverse cues. Thus, highveld mole-rats (Cryptomys hottentotus pretoriae) are social bathyergids in which breeding is restricted to a particular season in the dominant female, but continuously suppressed in subordinate colony members. Elucidation of reproductive control in these animals will be facilitated by characterization of their GnRH1 gene. A partial sequence of GnRH1 precursor cDNA was isolated and characterized. Comparative analysis revealed the highest degree of identity (86%) to guinea pig GnRH1 precursor mRNA. Nevertheless, the deduced amino acid sequence of the mole-rat decapeptide is identical to the 'mammalian' sequence rather than that of guinea pigs. Successful detection of GnRH1-synthesizing neurones using either a guinea pig GnRH1 riboprobe or an antibody against the 'mammalian' decapeptide is consistent with the guinea pig-like sequence for the precursor and the classic 'mammalian' form for the decapeptide. The high degree of identity in the GnRH1 precursor sequence between this Old World mole-rat and the New World guinea pig is consistent with the theory that caviomorphs and phiomorphs originated from a common ancestral line in the Palaeocene to mid Eocene, some 63-45 million years ago.

Ageing and the diurnal expression of mRNAs for vasoactive intestinal peptide and for the VPAC2 and PAC1 receptors in the suprachiasmatic nucleus of male rats.

Ageing alters fundamental aspects of circadian rhythmicity in mammals; the effects include reduced rhythm amplitude and alterations in period length and in entrainment to the light/dark cycle. Such changes may reflect disruptions in cellular function within the suprachiasmatic nucleus (SCN), the site of the predominant circadian pacemaker. In the SCN, vasoactive intestinal peptide (VIP)-synthesizing neurones receive various inputs, including retinohypothalamic projections containing pituitary adenylate cyclase activating peptide (PACAP). SCN VIP cells establish connections with local neurones and send efferents beyond the nucleus. Considerable evidence implicates VIP and PACAP in circadian rhythm maintenance and/or entrainment to photic Zeitgebers. These actions involve members of a distinct family of receptors; mRNAs for two such receptors, VPAC2 and PAC1, are present in the SCN. This study used isotopic in situ hybridization to examine the effects of ageing on expression of mRNAs for VIP, VPAC2 and PAC1 in the SCN of male rats under a 12 : 12 h light/dark cycle. Analysis of film autoradiographs from young adult (2-3 months) or aged (19-20 months) rats, at eight time points across the light/dark cycle, showed loss of diurnal rhythmicity and reduced levels for VIP mRNA in the aged group. A diurnal rhythm of VPAC2 receptor mRNA was present in both groups, but its levels were reduced in the aged rats. There were no differences between the two groups for PAC1 receptor mRNA expression. The present results indicate that ageing reduces VIP and VPAC2 receptor mRNA and eliminates diurnal expression of VIP mRNA within the SCN of aged male rats.

Ageing and the diurnal expression of the mRNAs for vasopressin and for the V1a and V1b vasopressin receptors in the suprachiasmatic nucleus of male rats.

Changes in the function of neuropeptide synthesizing cells within the suprachiasmatic nucleus (SCN), the site of the predominant circadian pacemaker, may underlie the disturbance of rhythms observed during ageing. Arginine vasopressin (AVP) is synthesized by nearly one-third of SCN neurones in the rat. This peptide has predominantly excitatory actions within the SCN mediated by V(1)-type receptors; the extent to which the V(1a) and/or V(1b) receptor subtypes are involved in SCN functions remains to be determined. The present study used isotopic in situ hybridization histochemistry to examine the effects of ageing on expression of mRNAs for AVP and V(1a) in the SCN and for V(1b) in the SCN and supraoptic nucleus (SON) of male rats kept under a 12 : 12 h light/dark cycle. Analysis of film autoradiographs from young adult (2-3-month-old; n = 40) or aged (19-20-month-old; n = 40) animals, at eight time points across the light/dark cycle, revealed an equivalent pattern and amplitude for the diurnal rhythm of AVP mRNA in the SCN of the young adult and aged groups. Both groups also displayed a significant diurnal rhythm in the expression of V(1a) receptor mRNA; however, the amplitude of this rhythm was reduced in the aged group, due to increased levels during the light phase and early part of night. Although the expression of V(1b) mRNA did not display a significant diurnal rhythm within the SCN or SON, persistently elevated levels for V(1b) mRNA were observed in the aged group at both sites.

Cellular expression of V1a vasopressin receptor mRNA in the female rat preoptic area: effects of oestrogen.

The preovulatory luteinizing hormone (LH) surge in female rats is dependent upon signals from the suprachiasmatic nucleus (SCN), the site of a dominant circadian pacemaker. Various lines of evidence indicate that arginine-vasopressin (AVP)-containing projections from the SCN to the preoptic area (POA) contribute to the production of the surge of LH-releasing hormone (LHRH). These actions may be mediated by V(1a) because the transcript for this AVP receptor subtype is predominant within the POA of the female rat. In this study, in situ hybridization histochemistry was used to examine V(1a) mRNA expression, either by itself or together with LHRH or glutamic acid decarboxylase 65 (GAD(65)) mRNA, within the POA of ovariectomized rats in the presence or absence of oestrogen. V(1a) mRNA was found in cells across the rostro-caudal axis of the POA; some were in close proximity to cells expressing LHRH mRNA. Coexpression of V(1a) and LHRH mRNAs was detected only very rarely. By contrast, cells with V(1a) mRNA commonly displayed GAD(65) mRNA. The density of V(1a) mRNA-expressing cells was particularly high within the anteroventral periventricular nucleus; at this site, V(1a) mRNA expression was elevated following oestrogen treatment. The present results indicate that V(1a)-mediated AVP actions may influence LHRH release via cells in the immediate vicinity of LHRH neurones and/or via oestrogen-regulated cells in the anteroventral periventricular nucleus, which is a site that lacks LHRH neurones but plays an essential role in initiating the preovulatory LH surge.

Studies on the neuroanatomical basis for stress-induced oestrogen-potentiated suppression of reproductive function: evidence against direct corticotropin-releasing hormone projections to the vicinity of luteinizing hormone-releasing hormone cell bodies in female rats.

Various studies implicate corticotropin-releasing hormone (CRH) as a mediator for the inhibitory effects of stress on reproduction. This study was designed to elucidate the underlying neuroanatomy. The retrograde tracer cholera toxin was picospritzed into the vicinity of the luteinizing hormone-releasing hormone (LHRH) perikarya. CRH neurones were examined for the tracer in the medial preoptic nucleus (MPO), bed nucleus of the stria terminalis (BST), paraventricular nucleus (PVN), central amygdaloid nucleus (CeM), parabrachial nucleus (PB) and additional locations. Retrograde label was not detected in CRH neurones at any of these sites; nevertheless, in the MPO and PB, abundant retrogradely-labelled perikarya intermingled with CRH neurones. In the BST, CeM and PVN, sites containing major CRH cell populations, retrogradely-labelled cells were scarce or absent; however, retrograde labelling was found in adjacent regions: lateral septum, medial amygdaloid nucleus and areas bordering the PVN. Double-label in situ hybridization for the mRNAs for LHRH and the CRH type-1 receptor (CRH-R1) identified the receptor transcript at sites rostral and lateral to the LHRH neurones (in the vertical and horizontal limbs of the diagonal band) but not in the LHRH neurones. Given the ability of oestrogen to potentiate stress-induced suppression of LH release, the identification of CRH neurones immunoreactive for oestrogen receptor (ER) alpha in the MPO and for ER beta in the caudal PVN may be significant. In this context, it is also noteworthy that CRH neurones within the MPO and PB which are, respectively, immunopositive and immunonegative for ER alpha, lie within the vicinity of retrogradely-labelled cells. The present findings suggest that the means by which CRH may mediate inhibitory effects of stressors on LH release do not involve direct CRH projections to LHRH neurones; the indirect means for such regulation, and the sites at which oestrogen may potentiate the inhibitory response, remain to be established.

Central orexin A has site-specific effects on luteinizing hormone release in female rats.

Orexin A stimulates GnRH release from hypothalamic explants in vitro. The sites of action of orexin A in the regulation of LH release have been investigated in vivo in ovariectomized rats that were given vehicle or estradiol benzoate (EB), with or without an injection of progesterone 48 h later. Orexin A was administered intrahypothalamically under Saffan anesthesia, 50 h after the EB or vehicle; its effects on plasma LH levels were monitored in sequential blood samples. Orexin A (1.0 microg/side) injected into the rostral preoptic area (rPOA) at the level of the organum vasculosum of the lamina terminalis had a stimulatory effect on LH release in EB-treated ovariectomized rats. When orexin A was injected into the medial POA (mPOA) or the arcuate/median eminence, it had an inhibitory effect on the LH surge that occurs in ovariectomized rats primed with EB plus progesterone. Orexin A injected into the mPOA also reduced LH levels in ovariectomized rats untreated with ovarian steroids. Both the stimulatory and inhibitory effects of orexin A were antagonized by SB334867A, a selective orexin 1 receptor antagonist. Furthermore, when given alone into the rPOA, this antagonist attenuated the LH surge induced by EB plus progesterone. Thus, orexin appears to have a dual effect on LH release, being stimulatory in the rPOA and inhibitory in the mPOA or arcuate/median eminence. Both effects may be mediated, at least in part, by the orexin 1 receptor. Double label immunohistochemistry revealed close appositions between orexin A immunoreactive varicosities and a small proportion of GnRH cell bodies in the rPOA. It is suggested that the stimulatory effect of orexin A on LH release may involve direct actions on GnRH neurons.