The role of hybrid FDG-PET/MRI on decision-making in presurgical evaluation of drug-resistant epilepsy.

BACKGROUND: When MRI fails to detect a potentially epileptogenic lesion, the chance of a favorable outcome after epilepsy surgery becomes significantly lower (from 60 to 90% to 20-65%). Hybrid FDG-PET/MRI may provide additional information for identifying the epileptogenic zone. We aimed to investigate the possible effect of the introduction of hybrid FDG-PET/MRI into the algorithm of the decision-making in both lesional and non-lesional drug-resistant epileptic patients. METHODS: In a prospective study of patients suffering from drug-resistant focal epilepsy, 30 nonlesional and 30 lesional cases with discordant presurgical results were evaluated using hybrid FDG-PET/MRI. RESULTS: The hybrid imaging revealed morphological lesion in 18 patients and glucose hypometabolism in 29 patients within the nonlesional group. In the MRI positive group, 4 patients were found to be nonlesional, and in 9 patients at least one more epileptogenic lesion was discovered, while in another 17 cases the original lesion was confirmed by means of hybrid FDG-PET/MRI. As to the therapeutic decision-making, these results helped to indicate resective surgery instead of intracranial EEG (iEEG) monitoring in 2 cases, to avoid any further invasive diagnostic procedures in 7 patients, and to refer 21 patients for iEEG in the nonlesional group. Hybrid FDG-PET/MRI has also significantly changed the original therapeutic plans in the lesional group. Prior to the hybrid imaging, a resective surgery was considered in 3 patients, and iEEG was planned in 27 patients. However, 3 patients became eligible for resective surgery, 6 patients proved to be inoperable instead of iEEG, and 18 cases remained candidates for iEEG due to the hybrid FDG-PET/MRI. Two patients remained candidates for resective surgery and one patient became not eligible for any further invasive intervention. CONCLUSIONS: The results of hybrid FDG-PET/MRI significantly altered the original plans in 19 of 60 cases. The introduction of hybrid FDG-PET/MRI into the presurgical evaluation process had a potential modifying effect on clinical decision-making. TRIAL REGISTRATION: Trial registry: Scientific Research Ethics Committee of the Medical Research Council of Hungary. TRIAL REGISTRATION NUMBER: 008899/2016/OTIG . Date of registration: 08 February 2016.

High Frequency and Intensity Rehabilitation in 641 Subacute Ischemic Stroke Patients.

OBJECTIVES: To determine the effects of exergaming on quality of life (QoL), motor, and clinical symptoms in subacute stroke patients. DESIGN: A pseudorandomized controlled trial, using a before-after test design. SETTING: University hospital. PARTICIPANTS: Subacute, ischemic stroke outpatients (N=3857), 680 of whom were randomized and 641 completed the study. INTERVENTIONS: We determined the effects of 5 times a week twice daily (EX2; 50 sessions; n=286) and once daily (EX1; 25 sessions; n=272) exergaming and low-intensity standard care (control [CON]; 25 sessions; n=83) on clinical, mobility, blood pressure (BP), and QoL outcomes. MAIN OUTCOME MEASURES: The primary outcome was Modified Rankin Scale. Secondary outcomes were activities of daily living, 5 aspects of health-related QoL, Beck Depression Inventory, 6-minute walk test (6MWT), Berg Balance Scale (BBS), and static balance (center of pressure). RESULTS: During exercise, the peak heart rate was 134, 134, and 126 beats per minute in the EX2, EX1, and CON groups, respectively. mRS improved similarly in the EX2 (-1.8; effect size, d=-4.0) and EX1 (-1.4; d=-2.6) groups, but more than in the CON group (-0.7; d=-0.6). QoL, Barthel Index, BBS, 6MWT, and standing posturography improved more in the EX2 group and the same in the EX1 and CON groups. Systolic and diastolic resting BP decreased more in the EX2 and EX1 groups than in the CON group. The intervention effects did not differ between men (n=349) and women (n=292). CONCLUSIONS: Twice daily compared with once daily high-intensity exergaming or once daily lower intensity standard care produced superior effects on clinical and motor symptoms, BP, and QoL in male and female subacute ischemic stroke participants.

Novel frameshift mutation of the NR0B1(DAX1) in two tall adult brothers.

NR0B1 (nuclear receptor subfamily 0, group B, member 1) is a transcription factor encoded by DAX1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) responsible for the development and maintenance of the steroidogenic tissues. In humans the DAX1 mutations cause congenital adrenal hypoplasia (AHC) and hypogonadotropic hypogonadism (HHG) in boys. Here we report two brothers who were assessed by endocrinologist at the age of 51 and 43 because of their serious osteoporosis. They had been substituted with prednisolone since the age of 4 and 9 years because of their primary adrenal insufficiency (PAI). Due to their late puberty caused by HHG at the age of 16 and 17 years their heights were - 3.1 and - 3.3 SD, but then they had a significant growth during their adulthood and reached the + 1.85 SD and + 3.78 SD respectively. During this period, they received glucocorticoid supplementation, but the treatment of their HHG was inadequate. At the age of 51 and 43 years insulin tolerance test (ITT) and gonadotropin releasing hormone (GnRH) test confirmed their PAI and HHG. Genetic test performed at this time revealed a novel, four nucleotides deletion (del.586-571c.GGGC or 572-575c.GGGC) of DAX1 gene. The two brothers with AHC and HHG caused by a novel DAX1 mutation, reached tall final heights, despite of the disadvantageous prednisolone treatment during their childhood. We assume that the long-term lack of the sexual hormone substitution was a significant reason of their above average height as well as their serious osteoporosis.

[Hungarian clinical application opportunities of PET/MR imaging and first experiences]. / A PET/MR képalkotás magyarországi klinikai alkalmazásának lehetoségei, elso tapasztalatai.

Hungary's first and still only multimodality PET/MR device is operating in the Health Center of Kaposvár University. The aim of our review article is to present the current Hungarian PET/MR imaging application opportunities, our available initial experiences with this novel multimodality imaging technique in malignant and non-malignant diseases and further potential targeted clinical fields of use are also addressed. Orv Hetil. 2018; 159(34): 1375-1384.

[Childhood sporadic type of hemiplegic migraine with arteria cerebri media hypoperfusion]. / Gyermekkori sporadikus hemiplegiás migrén arteria cerebri media hipoperfúzióval.

Hemiplegic migraine is a rare subtype of migraine that is associated with reversible motor weakness in the aura phase. This is an uncommon form of migraine usually starting in childhood. The purpose of this case report is to highlight the differential diagnostic difficulty of the first attack. We describe a case, where the fluctuating unilateral motor weakness and aphasia suggested that the patient had ischaemic stroke. Nevertheless the brain MRI and MR angiography, the measured 5-hydroxyindole acetic acid (5-HIAA) concentration changes and the spontaneously improving clinical status proved the diagnosis of hemiplegic migraine. The MRI and MR angiography was very beneficial in establishing the correct diagnosis in this case. To distinguish between the familiar and sporadic type of hemiplegic migraine further genetic tests can be carried out.

[NEUROINTERVENTIONAL TREATMENT OF ACUTE ISCHEMIC STROKE: OUR EXPERIENCE IN KAPOSVAR, HUNGARY]. / AZ AKUT ISCHAEMIÁS STROKE NEUROINTERVENCIÓS KEZELÉSÉVEL SZERZETT KAPOSVÁRI TAPASZTALATAINK.

AIM OF THE STUDY: In the present study, we report procedural and mid-term functional outcome data on the first 50 neurointerventional treatments of acute ischemic stroke in the Kaposi Mór County Hospital, Kaposvár, Hungary. MATERIALS AND METHODS: Endovascular recanalization of occluded large cervical and intracranial arteries was performed following an unsuccessful intravenous lysis or when intravenous lysis was contraindicated. A control cohort was retrospectively formed by analyzing data of 16 patients who has been unsuccesfully treated with iv. lysis before neurointervention was available in our hospital. RESULTS AND CONCLUSION: Recanalization rate was 84% and major complication rate was 2% in the neurointerventional group. Mid-term good functional outcome, defined as mRS 0-2, was achieved in 44% in the neurointerventional and in 13% in the intravenous lysis group, after 11.5 and 39.7 months follow-up period, respectively. Subgroup analysis revealed patient age as the strongest predictive factor of good functional outcome. Our data shows that neurointerventional treatment of acute ischemic stroke gives substantially improved functional outcome, in accordance with the results of the recently published international randomized trials.

Treatment of In-stent Restenosis of the Internal Carotid Artery Using Drug-eluting Balloons.

PURPOSE: In-stent restenosis (ISR) following internal carotid artery (ICA) stenting is relatively common with an estimated incidence of 5%. Treatment options include repeat angioplasty with conventional or drug-eluting balloons (DEB), repeat stent angioplasty and surgical intervention. Application of DEB in ISR of the coronary and peripheral arteries is an established method; however, data on DEB treatment of ICA ISR are sparse. In this work, results from a retrospective cohort of 45 patients harboring 46 ICA ISR lesions treated with DEB angioplasty are presented. METHODS: Clinical, procedural and imaging data from DEB angioplasty treatment of 46 high-grade ICA ISR lesions in 45 patients, performed between 2013 and 2021 were collected. A single type of DEB (Elutax, Aachen Resonance, Aachen, Germany) was used in all procedures. Imaging follow-up was performed by regular Doppler ultrasound (DUS), verified by computed tomography angiography (CTA) in cases suspicious for a recurrent ISR. RESULTS: Technical success was 100%. Intraprocedural and postprocedural complications were not encountered. Clinical follow-up was obtained in all patients. Recurrent stroke in the affected territory was not encountered. A recurrent ISR following DEB treatment was confirmed by DUS and CTA in 4/46 (8.7%) of the lesions and were retreated with DEB. A third recurrent ISR occurred in a single case (2%) and following a second DEB retreatment there were no signs of a fourth recurrence after 36 months follow-up. CONCLUSION: The use of DEB angioplasty is a safe and effective treatment of ICA ISR lesions, yielding significantly better results compared to other modalities. Randomized multicenter studies are warranted.

Pipeline embolization device (PED) for neurovascular reconstruction: initial experience in the treatment of 101 intracranial aneurysms and dissections.

INTRODUCTION: The purpose of this study was to evaluate the safety and efficacy of the recently available flow diverter "pipeline embolization device" (PED) for the treatment of intracranial aneurysms and dissections. METHODS: Eighty-eight consecutive patients underwent an endovascular treatment of 101 intracranial aneurysms or dissections using the PED between September 2009 and January 2011. The targeted vessels include 79 (78%) in the anterior circulation and 22 (22%) in the posterior circulation. We treated 96 aneurysms and 5 vessel dissections. Multiple devices were implanted in 67 lesions (66%). RESULTS: One technical failure of the procedure was encountered. Immediate exclusion of the target lesion was not observed. Angiographic follow-up examinations were carried out in 80 patients (91%) with 90 lesions and revealed complete cure of the target lesion(s) in 47 (52%), morphological improvement in 32 lesions (36%), and no improvement in 11 lesions (12%). Six major complications were encountered: one fatal aneurysm rupture, one acute and one delayed PED thrombosis, and three hemorrhages in the dependent brain parenchyma. CONCLUSION: Our experience reveals that the PED procedure is technically straightforward for the treatment of selected wide-necked saccular aneurysms, fusiform aneurysms, remnants of aneurysms, aneurysms with a high likelihood of failure with conventional endovascular techniques, and dissected vessels. While vessel reconstruction, performed after dissection, is achieved within days, remodeling of aneurysmal dilatations may take several months. Dual platelet inhibition is obligatory. Parenchymal bleeding into brain areas dependent on the target vessel is uncommon.

Endovascular Recanalization of Tandem Internal Carotid Occlusions Using the Balloon-assisted Tracking Technique.

PURPOSE: Tandem occlusive lesions are responsible for up to 20% of acute ischemic stroke cases and are associated with poor prognosis if complete recanalization cannot be achieved. Endovascular recanalization might be challenging due to difficulties in the safe passage of the occluded plaque at the origin of the internal carotid artery (ICA). The balloon-assisted tracking technique (BAT), where a partially deflated balloon is exposed out of the catheter tip to facilitate its passage through stenosed or spastic arterial segments was introduced by interventional cardiologists and the applicability of the technique has been recently proposed in the field of neurointervention as well. Here we describe our experience using the BAT technique in the endovascular recanalization of tandem occlusive lesions. METHODS: Procedures were performed from June 2013 to December 2020 in a single center. Baseline clinical and imaging data, procedural and follow-up details and clinical outcomes were retrospectively collected. RESULTS: In this study 107 patients, median age 66 years, median admission NIHSS 14 and median ASPECTS 8 were included. Successful recanalization of the ICA using the BAT technique was achieved in 100 (93%) and successful intracranial revascularization in 88 (82%) patients. There were no complications attributable to the BAT technique. Intraprocedural complications occurred in 9 (8%) patients. Emergent stenting was performed in 40 (37%) at the end of the procedure. Postprocedural adverse events (intracerebral hemorrhage [ICH], malignant infarction) occurred in 6 (5%) patients. Good clinical outcome at 3 months (modified Rankin scale [mRS] 0-2) was 54 (50%) and mortality 26 (24%). Delayed stent placement during follow-up occurred in 21 cases. CONCLUSION: Application of BAT technique in tandem occlusions appears feasible, safe, and efficient. Further evaluation of this technique is awaited.

PET/MRI in the Presurgical Evaluation of Patients with Epilepsy: A Concordance Analysis.

The aim of our prospective study was to evaluate the clinical impact of hybrid [18F]-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ([18F]-FDG PET/MRI) on the decision workflow of epileptic patients with discordant electroclinical and MRI data. A novel mathematical model was introduced for a clinical concordance calculation supporting the classification of our patients by subgroups of clinical decisions. Fifty-nine epileptic patients with discordant clinical and diagnostic results or MRI negativity were included in this study. The diagnostic value of the PET/MRI was compared to other modalities of presurgical evaluation (e.g., electroclinical data, PET, and MRI). The results of the population-level statistical analysis of the introduced data fusion technique and concordance analysis demonstrated that this model could be the basis for the development of a more accurate clinical decision support parameter in the future. Therefore, making the establishment of "invasive" (operable and implantable) and "not eligible for any further invasive procedures" groups could be much more exact. Our results confirmed the relevance of PET/MRI with the diagnostic algorithm of presurgical evaluation. The introduction of a concordance analysis could be of high importance in clinical and surgical decision-making in the management of epileptic patients. Our study corroborated previous findings regarding the advantages of hybrid PET/MRI technology over MRI and electroclinical data.

Successful endovascular treatment of simultaneous acute ischaemic stroke and hyperacute ST-elevation myocardial infarction: the first case report of a single-operator cardio-cerebral intervention.

BACKGROUND: The simultaneous management of cardio-cerebral infarctions is an extremely difficult task, as both organs need to receive reperfusion therapy in a limited time to avoid death or permanent disability. The following case is the first published endovascular treatment of synchronous heart and brain infarctions delivered by a single operator with excellent clinical outcome. CASE SUMMARY: A 67-year-old female patient was directly transported to the emergency room of a comprehensive stroke centre with acute onset global aphasia and right hemiplegia. The onset to admission time exceeded the 4.5-h time window of systemic thrombolysis. Head computed tomography (CT) excluded extensive early extensive brain damage, CT angiography documented left middle cerebral artery occlusion and mechanical thrombectomy was indicated. Extensive anterior ST elevation was detected on the transport monitor while waiting for in-hospital transfer. The two simultaneously evolving pathologies were handled in a single endovascular procedure that took less than 60 min by a dual-trained interventional cardiologist/neurointerventional surgeon. The patient recovered without any major cardiac or neurologic sequela. DISCUSSION: Interventional cardiologists, professionally trained through a neurointerventional fellowship programme to perform endovascular stroke interventions according to the latest multi-society position paper, could not only complement stroke teams lacking manpower, but their unique experience could also help the patients suffering from the most devastating forms of cardio-cerebral infarctions.

Screening Methods for Diagnosing Cystic Fibrosis-Related Diabetes: A Network Meta-Analysis of Diagnostic Accuracy Studies.

BACKGROUND: Cystic fibrosis-related diabetes (CFRD) has become more common due to higher life expectancy with cystic fibrosis. Early recognition and prompt treatment of CFRD leads to improved outcomes. METHODS: We performed a network meta-analysis (NMA) in order to identify the most valuable diagnostic metrics for diagnosing CFRD out of available screening tools (index test), using the oral glucose tolerance test as a reference standard. Pooled sensitivity (Se), specificity (Sp), and superiority indices were calculated and used to rank the index tests. RESULTS: A total of 31 articles with 25 index tests were eligible for inclusion. Two-day, continuous glucose monitoring (CGM) ranked the highest (Se: 86% Sp: 76%), followed by glucose measurement from blood capillary samples (Se: 70%, Sp: 82%) and three-day CGM (Se: 96%, Sp: 56%). When we compared the CGM of different durations, two-day CGM performed best (Se: 88%, Sp: 80%), followed by three-day (Se: 96%, Sp: 59%) and six-day CGM (Se: 66%, Sp: 79%). CONCLUSIONS: Considering its overall performance ranking, as well as the high sensitivity, two-day CGM appears to be a promising screening test for CFRD.

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Macimorelin in Children with Suspected Growth Hormone Deficiency: An Open-Label, Group Comparison, Dose-Escalation Trial.

BACKGROUND/AIMS: Diagnosis of growth hormone deficiency (GHD) in children requires the use of provocative growth hormone (GH) stimulation tests, which can have limited reliability and are potentially contraindicated in some patients. This is the first paediatric study to test the safety, tolerability, and pharmacokinetics (PK)/pharmacodynamics (PD) of macimorelin, an oral GH secretagogue, approved for diagnosis of adult GHD. METHODS: In this open-label, group comparison, single-dose escalation trial (EudraCT 2018-001988-23), sequential cohorts of patients (C1-C3) received ascending single doses of macimorelin: 0.25 (C1), 0.5 (C2), and 1.0 (C3) mg/kg. Primary endpoints were safety and tolerability, and secondary endpoints were PK/PD. RESULTS: Twenty-four patients aged between 2 and <18 with suspected GHD participated in the study. No macimorelin-related adverse events were reported, and macimorelin was well tolerated. Plasma macimorelin concentrations increased with dose: mean areas under the curve were 6.69 (C1), 18.02 (C2), and 30.92 (C3) h × ng/mL; mean maximum concentrations were 3.46 (C1), 8.13 (C2), and 12.87 (C3) ng/mL. GH concentration increased following macimorelin administration: mean times of maximum measured concentration were 52.5 (C1), 37.5 (C2), and 37.5 (C3) min. CONCLUSION: All 3 doses of macimorelin had excellent safety and tolerability with PK/PD profiles in expected ranges. These results support the use of 1.0 mg/mL macimorelin in a Phase 3 test validation trial in children.

Treatment of intracranial atherosclerotic arterial stenoses with a balloon-expandable cobalt chromium stent (Coroflex Blue): procedural safety, efficacy, and midterm patency.

INTRODUCTION: We evaluated the coronary balloon-expandable cobalt chromium stent Coroflex Blue for the treatment of intracranial atherosclerotic arterial stenoses (IAAS). METHODS: Between March 2007 and October 2007, a total of 25 patients (20 male, age median 67 years) with 30 IAAS underwent endovascular treatment using Coroflex Blue stents (B. Braun, Germany). Location and degree of target stenoses before and after treatment and at follow-up and adverse clinical sequelae of treatment were registered. Angiographic follow-up was scheduled for 6, 12, 26, and 52 weeks after the treatment. RESULTS: The 30 treated lesions were located as follows: nine in intracranial-extradural internal carotid artery (ICA), three in intradural ICA, five in middle cerebral artery, eight in intradural vertebral artery, and five in basilar artery. The technical success rate was 100%. The degree of stenoses prior to and after treatment was 61 +/- 2% and 26 +/- 3% (mean +/- SE), respectively. A residual stenosis of <50% was achieved in 29 (97%) procedures. Treatment was uneventful in 28 out of 30 procedures (93%); one patient suffered a transient and one patient a permanent neurological deficit. Angiographic follow-up was available in all of the patients (100%) after 15.2 months (median) and showed significant (i.e., more than 50%) degree of recurrent stenosis in 11 (37%) of the lesions. Retreatment was performed in 11 (37%) lesions. CONCLUSION: The Coroflex Blue stent is easily inserted and safely deployed into intracranial arteries. The incidence of recurrent stenoses remains a concern. Stringent angiographic and clinical follow-up and retreatment are therefore mandatory.

[Bilateral testicular tumor in a young man with congenital 11ß-hydroxylase deficiency]. / 11-ß-hidroxiláz enzim defektusában szenvedo fiatal férfi kétoldali heredaganata.

Adrenal rest tumor presenting as palpable testicular mass has been well described in boys and adult males with congenital adrenal hyperplasia. It develops most commonly in patients with 21- hydroxylase deficiency, but the entity may also occur in rare forms of congenital adrenal hyperplasia, including 11ß-hydroxylase deficiency. Because the management of testicular adrenal rest tumors is substantially different from that applied in benign and malignant testicular tumors, an accurate differentiation between these entities is particularly important. Authors present the history of a young adult male with 11ß-hydroxylase deficiency who developed adrenal rest tumors presenting as palpable bilateral testicular masses during treatment with glucocorticoids, then testicular masses showed a rapid regression after an adequate glucocorticoid treatment. Considering lessons obtained from this case, authors review the pathomechanism, symptoms, as well as current diagnostic and treatment modalities of testicular adrenal rest tumors.

Coronary stent implantation for acute basilar artery occlusion with underlying stenosis.

AIMS: Our aim was to study the effectiveness of coronary stent implantation during the endovascular treatment (EVT) of acute basilar artery occlusion (BAO) with occlusion-underlying intracranial atherosclerotic stenosis (ICAS). METHODS AND RESULTS: We retrospectively analysed 91 consecutive BAO patients who underwent EVT between February 2014 and January 2019 in a single, high-volume neurointerventional centre. We studied the effect of immediate coronary stent implantation on the clinical outcome of BAO with occlusion-underlying stenosis. BAO patients with underlying ICAS (n=41) were characterised by longer symptom-onset-to-reperfusion times (231 min vs 173 min, p=0.0020), lower TICI 2b-3 reperfusion rates (65.85% vs 90.00%, p=0.0084), and higher overall mortality (HR 2.021, p=0.0417) compared to the BAO cases without ICAS (n=50). The patients undergoing stenting (n=18) had lower residual basilar artery (BA) stenosis (14.7% vs 81.0%, p<0.0001), higher chance for functional recovery (OR 7.6, p=0.0250) and higher chance of survival (HR 4.163, p=0.0026) compared to the BAO-ICAS cases treated without coronary stents (n=21). CONCLUSIONS: The immediate treatment of the occlusion-underlying stenosis with coronary stents and dual antiplatelet therapy (DAPT) in BAO was associated with improved overall survival and better functional outcomes.

Effects of intra- and extracellular space properties on diffusion and T(2) relaxation in a tissue model.

The purpose of this study was to investigate the effects of biophysical factors on the diffusion and the relaxation time T(2) independently. Certain properties of the extracellular and the intracellular space may change radically in pathological conditions resulting in water diffusion changes. A tissue model consisting of red blood cells was studied. The extra- and intracellular spaces were modified osmotically and by suspending medium concentration. Diffusion measurements were evaluated with regard to the effective medium theory. Neither the nature of the protein in the extracellular space nor an increased level of intracellular hydration caused a significant net water diffusion change in the cell suspension. The relaxation time T(2) exhibited very little dependence on the extracellular volume fraction or the concentration or the nature of the protein in the extracellular space. An increased level of intracellular hydration resulted in systematically larger T(2) values. It seems probable that increases in extracellular protein concentrations or in the extent of intracellular hydration do not play a significant role in the diffusion changes detected in pathological conditions. T(2) appears to depend on the level of hydration or the total water content but is seemingly less dependent of the concentration and the nature of the extracellular protein in our model solutions.

Benzamil prevents brain water accumulation in hyponatraemic rats.

BACKGROUND: It has been recently shown that A6 cells exposed to hyponatraemic stress respond with increased sodium uptake via activation of benzamil-sensitive sodium channels. This study was performed, therefore, to explore the possible involvement of benzamil-sensitive sodium channels and cellular sodium influx in brain oedema formation in hyponatraemic rats. METHODS: Four groups of male Wistar rats were studied (n = 13 in each group). Animals in group I with normonatraemia received intracerebroventricular (icv) 0.9% NaCl; animals in group II-IV were made hyponatraemic by intraperitoneal administration of isotonic glucose solution in a dose of 20% per body weight. Rats were pretreated with icv 0.9% NaCl (group II), 120 microg arginine vasopressin (AVP) (group III) or 4 microg benzamil-hydrochloride (group IV). Plasma sodium (ion-selective electrode) plasma osmolality (vapour pressure osmometer) and brain sodium and potassium content (flame photometer) as well as brain water content (desiccation method) were measured after a 2-h hydration period. RESULTS: Plasma sodium, osmolality and tissue sodium and potassium contents were markedly depressed in hyponatraemic rats (group II-IV, p < 0.0005 for each group) irrespective of drug pretreatment. Brain water content, however, responded to hyponatraemia with an increase from 77.55 +/- 1.00% to 78.45 +/- 0.94% (p < 0.01), and it was further augmented to 79.35 +/- 0.80% (p < 0.0005) by icv AVP pretreatment. By contrast, benzamil administration prevented the rise of brain water caused by hyponatraemia (77.61 +/- 1.04%). CONCLUSION: Early in the course of hyponatraemia, brain sodium channels may be activated, and the subsequent cellular sodium uptake may generate osmotic gradient to allow passive water flow into the cells. The simultaneous reduction of osmotic water conductivity of brain-specific aquaporin-4 by hyponatraemia, however, may limit water accumulation.

[Evaluation of the accuracy of inferior petrosal sinus sampling in the differential diagnosis of ACTH-dependent Cushing's syndrome]. / Sinus petrosus inferior katéterezés értékelése az adrenokortikotrop hormon dependens Cushing-szindróma elkülöníto diagnosztikájában.

The differentiation of adrenocorticotropic hormone producing pituitary adenoma (Cushing's disease) from the ectopic ACTH syndrome is always a complex and difficult task, and in rare cases it is not possible to differentiate between the two disorders, even with the use of dynamic endocrine tests and the most advanced imaging techniques. Inferior petrosal sinus sampling (IPSS) with subsequent ACTH measurements became the gold-standard method of the differential diagnostic process. 34 patients with ACTH dependent Cushing's syndrome in whom the source of ACTH secretion couldn't be identified unambiguously with imaging techniques and/or dynamic endocrine tests underwent altogether 41 IPSS between 1999 and 2005. The sensitivity of the method was calculated on the basis of 31 samplings of 25 patients who had definite endocrinological diagnosis confirmed by the recovery from Cushing's syndrome after surgical intervention and/or by histological examinations (22 patients with ACTH-producing pituitary adenoma and 3 patients with ectopic ACTH syndrome). As a result of IPSS, pituitary-dependent Cushing's disease was diagnosed with a baseline central to peripheral ACTH ratio of >2.0 or with a ratio of >3.0 after corticotropin releasing hormone (CRH) administration. IPSS correctly identified ACTH-producing pituitary adenoma in 20 of 28 sampling procedures, with a sensitivity of 71.4%. Three patients had true negative and 8 had false negative results. There was no false positive result. Four of the 8 patients with false negative first sampling had a repeat sampling procedure leading to true positive result in each patient. In patients with Cushing's disease having true positive interventions, the basal and 5 minutes post-CRH ACTH concentrations were diagnostic in 14 and 19 cases, respectively. The sensitivity of IPSS within this series, reported for the first time from Hungary, was lower than it was found in much larger series published in international literature. In addition to technical difficulties, the lower sensitivity can be accounted also for the highly selected nature of the patient group.

Fetal development of membrane water channel proteins aquaporin-1 and aquaporin-4 in the human brain.

Aquaporin-1 and aquaporin-4, water channel membrane proteins reported in both experimental animals and in adult humans, have been detected in different, non-overlapping areas of the central nervous system. This immunohistochemical study describes the developmental expression pattern of the water channel membrane proteins, aquaporin-1 and aquaporin-4, in various structures of human fetal brain over the gestational period of 14-40 weeks. Aquaporin-1 immunostaining was exclusively found in the epithelial cells of the choroid plexus from the 14th gestational week, and the staining pattern altered slightly over time. At week 14, immunostaining appeared only in the apical cell membranes. By the 18th gestational week, the entire plasma membrane of these apical cells was immunopositive, as well as was the cytosol. These changes in immunoreactivity indicate an increasing production of aquaporin-1 in the epithelial cells during the period between the 14th and 24th weeks of gestation. Aquaporin-4 immunostaining was first detected in the archicortex, from gestational week 14 and was detected in the neocortex, 6-7 weeks later. Immunostained structures were always astrocytes, particularly the astrocytic endfeet in the ventricular wall, at the developing ependymal lining, at the pial surface, and around the capillaries. Neuronal labeling was not observed. These results in human fetal brain lend morphological support to the previous findings that aquaporin-1 and aquaporin-4 play different roles in the regulation of the water homeostasis of the brain.