Gender specific association of decreased bone mineral density in patients with epilepsy

Objective To evaluate whether epilepsy or certain antiepileptic drugs render patients prone to develop low bone mineral density (BMD) and osteoporosis risk. Methods Thirty-eight (27 males, 11 females) consecutive adult epileptic patients receiving antiepileptic drugs (AEDs) and 71 control individuals matched for race, gender, age and body mass index (BMI) were subjected to dual energy X-ray absorptiometry (DXA). Results The mean lumbar spine and total hip BMD values were lower in the patients compared to control group (0.90±0.24g/cm2 vs 1.04±0.14g/cm2, p<0.001 and 0.92±0.14g/cm2 vs 0.99±0.13g/cm2, p=0.02, respectively). At the same skeletal sites, male patients had significantly reduced BMD compared to control males (0.90±0.21g/cm2 vs 1.03±0.15g/cm2, p=0.004 and 0.93±0.14g/cm2 vs 1.02±0.13g/cm2, p=0.009, respectively) while there was a trend but no significant differences in females. This BMD reduction was independent of AED type. Conclusion Adult epileptic, predominantly male patients have lower BMD and could be screened with densitometry for early diagnosis and prevention of osteoporosis

Myocardial perfusion imaging single photon emission computed tomography may detect silent myocardial ischemia in patient with epilepsy

Background: The aim of the present study was to compare the myocardial perfusion imaging (MPI) with [99mTc]tetrofosmin stress — rest single-photon emission computer tomography (SPECT) of patients with epilepsy with matched control individuals. Material and methods: All 29 adult epileptic patients were receiving antiepileptic drugs (AEDs) for epilepsy. Thirty-two individuals matched for gender and age consisted of the control group. MPIs SPECT were performed, and myocardial summed scores were obtained during stress (SSS) and rest (SRS) images. Abnormal MPI was considered when SSS was ≥ 4. In addition, the difference (SDS) between SSS and SRS was also assessed, which represents a rate of reversibility after stress. Results: Twenty of 29 (68.97%) patients with epilepsy had abnormal MPI and 14/32 (43.75%) of the controls (p = 0.04). Among males, 18/23 patients and 11/25 controls had abnormal MPI (p = 0.01), with quite a significant difference for mean SSS between male patients and controls (p = 0.002). Furthermore, SDS comparison showed that irreversible abnormalities were more common in patients than in control individuals. A difference of inadequately compensated myocardial ischemia between patients treated with enzyme inducing AEDs and patients treated with valproic acid was also detected. Conclusions: Single-photon emission computer tomography (SPECT) may detect increased risk for coronary artery disease and further cardiovascular events in patients with epilepsy. Our findings favor the conclusion that SPECT could be used for the early identification of cardiovascular comorbidity in epilepsy

Vitamin D receptor gene polymorphisms in multiple sclerosis patients in northwest Greece

<p>Abstract</p> <p>Background</p> <p>Polymorphisms of the vitamin D receptor (VDR) gene have been linked to both multiple sclerosis (MS) and osteoporosis. We examined the frequency of the Taq-I and Bsm-I polymorphisms of the vitamin D receptor (VDR) gene in 69 patients with MS and 81 age and sex-matched healthy individuals. Genotyping of Taq-I (rs731236) and Bsm-I (rs1544410) was performed using TaqMan^®SNP Genotyping Assay. All patients and controls had determination of body mass index (BMI), bone mineral density (BMD) and smoking history.</p> <p>Results</p> <p>The mean age of patients was 39 ± 10.5 years compared to 38.7 ± 10.7 years of the controls (p = 0.86), the BMI was 24.8 ± 4.2 kg/m²compared to 25.7 ± 4.8 kg/m²of the controls (p = 0.23), the BMD in the lumbar spine 0.981 ± 0.15 compared to 1.025 ± 013 of the controls (p = 0.06) and the total hip BMD was 0.875 ± 0.14 compared to 0.969 ± 0.12 of the controls (p < 0.001). There were no differences of the Taq-I (TT, CT, CC) and Bsm-I genotypes (GG, GA, AA) and allelic frequencies between MS and control individuals. Multivariate analysis also failed to show any association of the Taq-I and Bsm-I polymorphisms and MS or sex, BMI, BMD and smoking history.</p> <p>Conclusions</p> <p>This study suggests that the Taq-I and Bsm-I polymorphisms of the VDR gene are not associated with MS risk, BMI or BMD in the Greek population studied.</p

I/D polymorphisms of angiotensin converting enzyme (ACE) and stroke

Polymorphisms of the RAS genes and in particular the ACE I/D have been associated or have been tested for associations with a variety of multifactorial disorders, such as hypertension, preeclampsia, coronary artery disease, diabetic nephropathy or IgA nephropathy, intracranial hemorrhage and ischemic stroke. Regarding ischemic stroke, a number of studies has focused on the association of genotypes and I/D alleles with stroke incidence, the stroke subtype, the age at insult, the clinical severity, the morbidity, the coexistence of arterial hypertension, the carotid stenosis, the intima media thickness (IMT) and other critical parameters with conflicting results. Amidst the bulk of different studies with positive and negative outcomes, we enrolled prospectively stroke patients, up to the age of 70, referred and hospitalized at the University Hospital of Ioannina and in particular at the Department of Neurology, for a period of 36 months, in order to reevaluate almost all the important parameters from the literature, in relation to their genetic background (ACE-I/D) in our virtually isolated population of Northwest Greece. Having excluded other potential causative entities for the development of ischemic stroke, as for example immunological disorders, embolism and coagulation disorders, we focused on a sample size of 176 patients, 60 females and 116 males, and a control sample of 178 individuals matched for age and gender, with similar known predisposing factors for ischemic stroke. A full clinical and laboratory assessment was performed in all patients, with report and classification of demographical data, disease and family history. In all patients and controls apart from the collection of similar data, DNA was extracted and stored for analysis The results concerning comparisons of the two groups (patients and controls) were statistically negative as regards incidence, stroke subtype, age, age at first stroke, severity, recurrence, hypertension, weight (and related indexes) and IMT. Statistically significant result was present when the comparisons were performed separately in regard to patient and control gender. Women with II homozygozity had a lower risk for ischemic stroke, as compared to male patients and healthy control females (p=0.038, OR= 0.1137 and p= 0.0251, OR= 0.1853 respectively). The same statistical analysis revealed that the D allele is predisposing in women and protective in men for ischemic stroke. Only few reports exploring the I/D polymorphism have studied the differential distribution of genotypes and alleles between the two genders and none has reported these differences in ischemic stroke. We know for example that DD homozygozity has been associated with higher levels of angiotensin in women and that is also responsible for abdominal aortic aneurisms in women, but as concerns ischemic stroke and gender specific predisposition, there is still lack of evidence. Support for the results of this thesis is provided by the accredited bibliography accumulated on the incidence of ischemic stroke differences between sexes that have different physiology, genetic background, differences in steroid hormone receptor tissue distributions and other related differences. In particular evidence strongly support that estrogen regulates ACE mRNA transcription, also in relation to ACE I/D polymorphism. Regardless the exact and in detail pathophysiology of gender specific stroke incidence, many sex influenced genes, as for example ACE I/D genotypes and alleles, should be considered in many more female samples, or in many more samples of both sexes, in order to reassure power and validity of sex differences in ischemic stroke.Οι πολυμορφισμοί του συστήματος ρενίνης - αγγειοτενσίνης - αλδοστερόνης, και κυρίως ο πολυμορφισμός Ι/D του μετατρεπτικού ενζύμου, έχουν συσχετισθεί ή έχει γίνει προσπάθεια να συσχετιστούν με την επίπτωση και τη βαρύτητα διαφόρων νόσων, όπως είναι η υπέρταση, η προεκλαμψία, η στεφανιαία νόσος, η διαβητική νεφροπάθεια, η IgA νεφροπάθεια, η ενδοεγκεφαλική αιμορραγία και τα ισχαιμικά αγγειακά εγκεφαλικά επεισόδια. Σε σχέση με τα αγγειακά εγκεφαλικά επεισόδια (ΑΕΕ), πολλές εργασίες μελετούν τη σχέση των γονοτύπων και των αλληλομόρφων Ι/D με την πιθανότητα εμφάνισης ΑΕΕ, τον τύπο του ΑΕΕ, την ηλικία των ασθενών, τη βαρύτητα του επεισοδίου και τη θνησιμότητα, τη συνύπαρξη αρτηριακής υπέρτασης, την παρουσία καρωτιδικών πλακών, το intima media thickness (ΙΜΤ) και άλλες παραμέτρους με αντικρουόμενα αποτελέσματα. Μέσα στον ορυμαγδό των διαφορετικών μελετών με τα ποικίλα αποτελέσματα, συγκεντρώσαμε τους ασθενείς με ισχαιμικά ΑΕΕ που νοσηλεύτηκαν στη Νευρολογική Κλινική του Πανεπιστημιακού Νοσοκομείου Ιωαννίνων, ηλικίας μικρότερης ή ίσης των 70 ετών, σε διάστημα 36 μηνών, προκειμένου να επανεξετάσουμε όλες σχεδόν τις γνωστές Βιβλιογραφικά παραμέτρους σε σχέση με το γενετικό τους υπόστρωμα ως προς τον I/D πολυμορφισμό, στο δικό μας κλειστό γεωγραφικά πληθυσμό της Βορειοδυτικής Ελλάδος. Αφού αποκλείσαμε άλλες πιθανές αιτίες, ως υπεύθυνες για πρόκληση του ισχαιμικού επεισοδίου, όπως είναι η ύπαρξη εμβολογόνου εστίας, η ύπαρξη ανοσολογικής διαταραχής ή διαταραχής του πηκτικού μηχανισμού, καταλήξαμε σε ένα σύνολο 176 ασθενών, 60 γυναικών και 116 αντρών, το οποίο συγκρίθηκε με 178 υγιή άτομα παρόμοιας ηλικίας και φύλου και με παρόμοιους γνωστούς προδιαθεσικούς παράγοντες στην πρόκληση ΑΕΕ. Στους ασθενείς αυτούς έγινε πλήρης κλινικός και παρακλινικός έλεγχος, καταγραφή των δημογραφικών στοιχείων και των στοιχείων του ιστορικού τους και εξαγωγή DNA προς προσδιορισμό του πολυμορφισμού που έφεραν. Καταγραφή δημογραφικών στοιχείων και στοιχείων του ιστορικού και εξαγωγή DNA διενεργήθηκε και στην ομάδα ελέγχου. Τα αποτελέσματα, που προέκυψαν από τις συγκρίσεις των δύο ομάδων, δεν ανέδειξαν στατιστικά σημαντικό αποτέλεσμα ως προς την επίπτωση των ΑΕΕ, την υποκατηγορία των ΑΕΕ, την ηλικία των ασθενών, την ηλικία εμφάνισης του πρώτου επεισοδίου, τη βαρύτητα και την επαναληψιμότητα των επεισοδίων, την υπέρταση, το βάρος των ασθενών και το ΙΜΤ των καρωτίδων. Σημαντικά στατιστικό αποτέλεσμα προέκυψε κατά την επεξεργασία των αποτελεσμάτων σε σχέση με το φύλο των ασθενών, με τις γυναίκες που φέρουν την II ομοζυγωτία να έχουν μειωμένο κίνδυνο να υποστούν ΑΕΕ, συγκρινόμενες με τους άντρες ασθενείς (p=0.038, OR=0.1137) και συγκρινόμενες με τις υγιείς γυναίκες της ομάδας ελέγχου (p= 0.0251, OR= 0.1853). Μέσα από την ίδια στατιστική ανάλυση προέκυψε το αλληλόμορφο D να δρα επιβαρυντικά στις γυναίκες (p=0.024, OR=0.024) και προφυλακτικά στους άντρες, ως προς την πρόκληση ΑΕΕ. Ελάχιστες μελέτες που αφορούν στον Ι/D πολυμορφισμό έχουν εξετάσει τη διαφορετική κατανομή των γονοτύπων και των αλληλομόρφων στα δύο φύλα και καμία δεν αφορά στην πρόκληση ΑΕΕ. Γνωρίζουμε για παράδειγμα ότι η ομοζυγωτία DD έχει συσχετιστεί με αυξημένα επίπεδα αγγειοτενσίνης στις γυναίκες και ότι ευθύνεται για πρόκληση ανευρύσματος κοιλιακής αορτής επίσης στις γυναίκες αλλά σε επίπεδο πρόκλησης ΑΕΕ και σύνδεσης των πολυμορφισμών με το φύλο έχουν πολλά να γίνουν ακόμη. Η απάντηση για το αποτέλεσμα, το οποίο προέκυψε στην παρούσα διδακτορική διατριβή, μπορεί να βρίσκεται στην αποδεδειγμένη Βιβλιογραφικά διαφορά στην επίπτωση των ΑΕΕ στα δύο φύλα, που φέρουν διαφορετικό γενετικό υλικό ως προς τους υποδοχείς των οιστρογόνων, και στη επίδραση των οιστρογόνων στους πολυμορφισμούς του RAS και συνεπώς και στον I/D πολυμορφισμό. Όποιος και αν είναι ο ακριβής παθοφυσιολογικός μηχανισμός, που ευθύνεται για τη διαφορετική επίπτωση ΑΕΕ στα δύο φύλα με διαφορετικούς γονοτύπους και αλληλόμορφα ως προς τον Ι/D πολυμορφισμό, θα πρέπει αυτός να διερευνηθεί σε Βάθος και να λάβουν χώρα μεγαλύτερες μελέτες με περισσότερους ακόμη πολυμορφισμούς και εστίαση στο διαχωρισμό θήλεων και αρρένων πασχόντων

An emerging problem in clinical practice: how to approach acute psychosis

Limbic encephalitis (LE) is rare, presents with memory impairment, seizures and behavioral disorder. We present a 44-year-old female with an agitation-depressive disorder associated with delusions and hallucinations, admitted to our hospital with the diagnosis of psychosis. A computed tomography (CT) scan of the brain and lumbar puncture on admission were normal. Because of clinical deterioration and addition of seizures in the clinical picture, further workup with serum and repeat cerebrospinal fluid studies, magnetic resonance imaging (MRI), and electroencephalogram disclosed a lesion in the left medial temporal lobe consistent with LE. The patient was treated symptomatically with antidepressive, antipsychotic and anticonvulsant drugs. Aggressive diagnostic tests for the presence of an occult cancer were negative. An 8-year follow up has not revealed a tumor to support a paraneoplasmatic origin of LE. This case, initially diagnosed and treated as psychosis, is a case of non-paraneoplasmatic, non-infective LE, probably caused by an autoimmune mechanism

Status epilepticus in scleromyxedema

Scleromyxedema is a rare dermatologic disorder, characterized by erythematous or yellowish lichenoid waxy papules. Neurological manifestations are rare but well-recognized. A 51-year-old woman, diagnosed with scleromyxedema, was admitted to the hospital with status epilepticus, caused by brain lesions, as disclosed in a brain magnetic resonance imaging (MRI). The patient was treated with anticonvulsants and corticosteroids and gradually recovered fully. A complete remission of the lesions was shown in a follow-up brain MRI. In cases with scleromyxedema and the presence of neurological manifestations, we need to pay attention to central nervous system involvement, especially when combined with brain MRI lesions, and treat the patient appropriately

Management of meningiomas

The primary treatment of meningiomas is surgery which can be curative if the tumor is completely removed. For parasagittal, lateral sphenoid wing and olfactory groove meningiomas, gross-total resection should be the goal. Tuberculum and diaphragma sella meningiomas can be resected through the subfrontal or the pterional approaches. In meningiomas of the sphenoid wing with osseous involvement or involvement of the cavernous sinus subtotal resection can be achieved via several surgical approaches. Similarly, subtotal resection rather than gross-total resection of meningiomas of the petroclival, parasellar, and posterior fossa regions can preserve neurological function. Prior to surgery, embolization may reduce intraoperative bleeding and prevent postoperative complications. Stereotactic radiosurgery can be used as an alternative treatment to surgery either as a first-line treatment or at recurrence. Various conventional radiotherapy techniques can be employed for residual tumor post surgery or at recurrence. Chemotherapy has modest activity and is reserved for selected cases. (C) 2009 Elsevier B.V. All rights reserved

Genetic and molecular alterations in meningiomas

Meningiomas are the most common benign intracranial tumors in adults arising from the dura matter. The etiology of meningiomas is mostly unknown, although several risk factors have been described, such as ionizing radiation, head injury, hormones and genetic factors. According to WHO they are classified into 3 grades, grade I, grade II and grade III. Meningiomas express various hormonal and growth factor receptors, such as progesterone, estrogen, somatostatin, transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) receptors, which may be related to their biological behavior and response to treatment. Chromosomal abnormalities linked to meningiomas involve chromosomes 22, 1p, 9p, 10p, 11, 14q, 15, 17, and 18q. In addition, genes that may be involved in the formation of meningiomas include NF2, DAL-1, p14 (ARF), p53, MDM2, Rb, p16 and c-myc. It is likely that detailed molecular information will aid in establishing a molecular grading of these tumors and predict response to treatment and survival. (C) 2010 Elsevier B.V. All rights reserved