Neurophysiological study of hemoglobinopathy patients and correlation of the findings with clinical and laboratory parameters of the disease

Hemoglobinopathies are among the most common hereditary blood diseases worldwide, with about 7% of the population being carriers of a mutation in the hemoglobin gene. Specifically, it is estimated that about 50.000 symptomatic infants with beta thalassemia major are born annually. Nowadays, the average life expectancy of patients in developed countries, has increased significantly while, there was an increase of complications as a result of either the disease itself or the intensive and long-term drug treatment patients receive. The aim of this thesis was to investigate the possibility to detect by neurophysiological methods, significant (measurable) lesions in the peripheral nervous system in patients and correlate with epidemiological data and clinical and laboratory parameters of the disease. In this survey 85 people were examined, of which 45 patients with hemoglobinopathies and 40 healthy volunteers, in order to determine the normal range in the measured neurophysiological parameters. The statistical analysis of the data included only patients with homozygous beta-thalassemia major, provided that they didn’t have or they had endocrinopathy (e.g., diabetes mellitus or thyroiditis) that was stable and well-controlled in the last 2 years, and additionally they were not suffering from autoimmune diseases, neoplastic diseases, nor were immunosuppressed, or Human Immunodeficiency Virus positive and without history of cerebral infraction. The average age of the 36 patients who met the inclusion criteria was 39.1 (range 16-57) and the group of healthy volunteers 40.4 (range 22-58). In the patients group 14 were men and 22 women, while in the control group 16 were men and 24 were women. Nerve conduction studies revealed that only 22.2% of patients had normal findings and the remaining patients had abnormal findings. Specifically, mononeuropathies, radiculopathies or mild lesions (possible mononeuropathy and limited damage to another nerve), were seen in 38.9% of the sample. Additionally, moderate or heavy polyneuropathy were recorded at a rate of 38.9%. Neuropathy was mainly mixed (motor and sensory) at a rate of 22.2%, followed by pure motor neuropathy with a percentage of 13.9%, while only 2.8% of all patients had pure sensory neuropathy. In addition, our study is the first study to our knowledge, that performed systematically electromyography in patients with thalassemia and revealed that 27.8% have myopathy. There was not statistically significant correlation of polyneuropathy or myopathy with age, sex, splenectomy, nor with respect to laboratory parameters, hemoglobin and ferritin. However, there was statistically significant correlation of polyneuropathy with iron overload, as recorded by the magnetic resonance imaging (MRI) of the heart and the liver, revealing the role of iron as a causative factor for polyneuropathy and myopathy. In conclusion, patients with beta thalassemia major, present polyneuropathy and myopathy at (38.9%) and (27.8%) respectively. Iron overload is the major aetiology for these lesions. The heart and liver MRI is the best and safest predictor for the prevention of such lesions and MRI performance in an annual basis is warranted.Οι αιμοσφαιρινοπάθειες συγκαταλέγονται ανάμεσα στις πιο κοινές κληρονομικές παθήσεις του αίματος, σε παγκόσμιο επίπεδο, με περίπου 7% του πληθυσμού να αποτελούν φορείς κάποιας μετάλλαξης του γονιδίου της αιμοσφαιρίνης. Ειδικότερα για τη Μεσογειακή αναιμία υπολογίζεται ότι περίπου 50.000 συμπτωματικά βρέφη γεννώνται σε ετήσια βάση. Τα τελευταία χρόνια, ο μέσος όρος ζωής των ασθενών στις αναπτυγμένες κοινωνίες έχει αυξηθεί σημαντικά και παράλληλα, παρατηρήθηκε και αύξηση των επιπλοκών, συνεπεία είτε της ίδιας της νόσου είτε της εντατικής και μακροχρόνιας φαρμακευτικής αγωγής που λαμβάνουν οι ασθενείς. Στόχος της παρούσας διδακτορικής διατριβής ήταν η διερεύνηση της πιθανότητας να ανιχνευθούν με νευροφυσιολογικές μεθόδους σημαντικές (μετρήσιμες) διαταραχές στο περιφερικό νευρικό σύστημα στους ασθενείς και να συσχετιστούν με τα επιδημιολογικά δεδομένα και τις κλινικοεργαστηριακές παραμέτρους της νόσου. Στην παρούσα έρευνα συμμετείχαν 85 άτομα, εκ των οποίων 45 ασθενείς με αιμοσφαιρινοπάθειες και 40 υγιείς εθελοντές, προκειμένου να προσδιοριστούν τα φυσιολογικά όρια στις μετρούμενες νευροφυσιολογικές παραμέτρους. Στη στατιστική ανάλυση των δεδομένων συμπεριλήφθηκαν μόνο οι ασθενείς με ομόζυγη β-μεσογειακή αναιμία, με την προυπόθεση ότι δεν είχαν ή είχαν ενδοκρινοπάθεια (π.χ., σακχαρώδης διαβήτης ή θυρεοειδοπάθεια) που τα τελευταία 2 χρόνια ήταν σταθερά, καλά ρυθμισμένη και δεν έπασχαν από αυτοάνοσα νοσήματα, νεοπλασματικά νοσήματα, ούτε ήταν ανοσοκατασταλμένοι, ή φορείς συνδρόμου ανοσοανεπάρκειας και δεν είχαν ιστορικό αγγειακού εγκεφαλικού επεισοδίου. Ο μέσος όρος της ηλικίας των 36 ασθενών, που πληρούσαν τα κριτήρια, ήταν 39,1 (εύρος 16-57) και της ομάδας των υγιών εθελοντών 40,4 (εύρος 22-58). Από την ομάδα των ασθενών (14) ήταν άνδρες και (22) γυναίκες, ενώ από την ομάδα ελέγχου (16) ήταν άνδρες και (24) γυναίκες. Ο νευροφυσιολογικός έλεγχος της αγωγιμότητας των νεύρων αποκάλυψε ότι μόνο το 22,2 % των ασθενών είχε φυσιολογικά ευρήματα και οι υπόλοιποι ασθενείς είχαν παθολογικά ευρήματα. Συγκεκριμένα, μονονευροπάθειες, ριζοπάθειες, ή ήπιες βλάβες (πιθανή μονονευροπάθεια και οριακή βλάβη σε ένα ακόμη νεύρο), παρατηρήθηκαν στο 38,9% του δείγματος. Μέτρια ή βαριά πολυνευροπάθεια καταγράφηκε σε ποσοστό 38,9%. Η πολυνευροπάθεια ήταν κατά κύριο λόγο μικτού τύπου (κινητική και αισθητική) σε ποσοστό 22,2% και ακολουθούσε η αμιγής κινητική πολυνευροπάθεια με ποσοστό 13,9%, ενώ μόλις 2,8% επί του συνόλου των ασθενών παρουσίαζε αμιγώς αισθητική πολυνευροπάθεια. Επιπρόσθετα, στη μελέτη μας πραγματοποιήθηκε για πρώτη φορά ηλεκτρομυογραφικός έλεγχος σε ασθενείς με μεσογειακή αναιμία και αποκαλύφθηκε ότι το 27,8% παρουσιάζει μυοπαθητικά ευρήματα.Από τη μελέτη των αποτελεσμάτων της έρευνας δεν προέκυψε στατιστικά σημαντική συσχέτιση της πολυνευροπάθειας ή της μυοπάθειας ως προς την ηλικία, το φύλο, τη διενέργεια ή μη σπληνεκτομής, αλλά ούτε και σε σχέση με τις εργαστηριακές παραμέτρους, αιμοσφαιρίνη και φερριτίνη. Ξεκάθαρη ήταν, ωστόσο, η συσχέτιση της πολυνευροπάθειας με τη φόρτιση σιδήρου, όπως αυτή καταγράφεται από τη μαγνητική τομογραφία (MRI) καρδιάς και ήπατος, αποκαλύπτοντας τον ρόλο του σιδήρου στην πρόκληση βλαβών του περιφερικού νευρικού συστήματος , αλλά και μυοπάθειας. Εν κατακλείδι, συμπεραίνουμε ότι οι ασθενείς με βήτα μείζονα μεσογειακή αναιμία, παρουσιάζουν σε πολύ υψηλά ποσοστά πολυνευροπάθεια (38,9%) και μυοπαθητικές αλλοιώσεις (27,8%). Ο σίδηρος, διαδραματίζει καθοριστικό αιτιοπαθογενετικό ρόλο στην πρόκληση αυτών των βλαβών. Η MRI καρδιάς και ήπατος αποτελεί τον καλύτερο και ασφαλέστερο προγνωστικό δείκτη για την πρόληψη των βλαβών και προτείνεται η χρήση της σε τακτική ετήσια βάση

Source localization of ictal epileptic activity based on high-density scalp EEG data

Electrical source imaging (ESI) is a well-established approach to localizing the epileptic focus in drug-resistant focal epilepsy. So far, ESI has been used primarily on interictal events. Emerging evidence suggests that ictal ESI is also feasible and potentially useful. We aimed to investigate the diagnostic accuracy of ESI on ictal events using high-density electroencephalography (EEG)

Antidepressant Use and Orthostatic Hypotension in Older Adults Living with Mild-to-Moderate Alzheimer Disease

Objectives: Antidepressant use is often reported as a risk factor for Orthostatic Hypotension (OH), however this relationship has never been explored in those with mild/moderate Alzheimer Disease (AD), who may represent a particularly vulnerable cohort. Methods: We performed a cross-sectional analysis of baseline data from the NILVAD study. Participants with mild-moderate AD were recruited from 23 centres in 9 countries. Systolic and Diastolic Blood Pressure (SBP/DBP) was recorded in the seated position and after both 1 & 5 minutes of standing. OH was defined as a drop of 6520 mmHg SBP/ 65 10 mmHg DBP. We examined the relationship between antidepressant use, orthostatic BP drop and the presence of OH, controlling for important covariates. Results: Of 509 participants (72.9 \ub1 8.3 years, 61.9% female), two-fifths (39.1%; 199/509) were prescribed a regular antidepressant. Antidepressant use was associated with a significantly greater SBP and DBP drop at 5 minutes (\u3b2: 1.83, 0.16-3.50, P = 0.03 for SBP; \u3b2: 1.13, 0.02-2.25, P < 0.05 for DBP). Selective Serotonin Reuptake Inhibitor (SSRI) use was associated with a significantly greater likelihood of OH (OR 2.0, 1.1-3.6, P = 0.02). Both findings persisted following robust covariate adjustment. Conclusions: In older adults with AD, antidepressants were associated with a significantly greater SBP/DBP drop at 5 minutes. SSRI use in particular may be a risk factor for OH. This emphasises the need to screen older antidepressant users, and particularly those with AD, for ongoing orthostatic symptoms in order to reduce the risk of falls in this vulnerable cohort. This article is protected by copyright. All rights reserved

Sedative Load in Community-Dwelling Older Adults with Mild-Moderate Alzheimer's Disease: Longitudinal Relationships with Adverse Events, Delirium and Falls

Background Older adults are frequently prescribed medications with sedative effects, which are associated with numerous adverse consequences. However, the prevalence and longitudinal associations of sedative medication use in community-dwelling older adults with mild-moderate Alzheimer's disease (AD) has not been explored to date. Objectives Our objective was to assess the prevalence of sedative medication use in community-dwelling older adults with mild-moderate AD and examine the longitudinal association between sedative medication use and adverse events (AEs). Methods The association between baseline sedative load (SL) and AEs, unscheduled healthcare utilisation, delirium and falls was assessed in older adults with mild-moderate AD over 18 months using secondary analysis of NILVAD trial data (collected from 2014 to 2016). Baseline medication use was assessed, and the SL model was applied to each participant's medication individually. The SL model classifies medications into one of four categories: (1) primary sedatives, (2) medications with a sedating component or prominent side effect, (3) medications with sedation as a potential adverse reaction and (4) all other medications with no known sedative side effects. Medications in group 1 were assigned an SL score of 2, those in group 2 were assigned an SL score of 1, and those in categories 3 and 4 an SL score of 0. SL scores for each medication participants were taking were summed and the total SL calculated as an arithmetic sum of individual medications score. A total SL score >= 3 was classed as high. Statistical analysis was conducted using Poisson regression and mixed-effects linear regression, with adjustment for important clinical covariates. We also assessed the impact of SL on dementia progression and cognitive decline. Results Over half (55.7% [284/510]) of those with mild-moderate AD (age 72.8 +/- 8.3 years, 61.9% female) were prescribed a regular medication with sedation as a primary effect or prominent side effect, with 22.2% (113/510) having a high SL (>= 3). The most common medications contributing to SL were antidepressants, antipsychotics, anxiolytics and hypnotics. Over 18 months, increasing baseline SL was associated with incident AEs (incidence rate ratio [IRR] 1.15; 95% confidence interval [CI] 1.11-1.19;p< 0.001), serious AEs (IRR 1.23; 95% CI 1.11-1.36;p< 0.001) and unscheduled general practitioner visits (IRR 1.23; 95% CI 1.13-1.34;p< 0.001). Further, increasing SL was associated with a greater likelihood of incident delirium (IRR 1.30; 95% CI 1.11-1.53;p< 0.001) and falls (IRR 1.20; 95% CI 1.03-1.42;p= 0.02). Associations persisted after robust covariate adjustment. SL was not associated with accelerated cognitive decline or AD progression. Conclusions In the current study, over half of older adults with mild-moderate AD were prescribed at least one drug with a sedative effect, and a significant minority had a high SL. Increasing baseline SL was associated with a greater likelihood of incident AEs, delirium and falls, highlighting the need for optimal prescribing in this potentially vulnerable cohort