Amelia Tartara

Bio: Amelia Tartara is an academic researcher from University of Pavia. The author has contributed to research in topics: Epilepsy & Sleep disorder. The author has an hindex of 28, co-authored 84 publications receiving 2377 citations.

Obstructive sleep apnea in a clinical series of adult epilepsy patients: frequency and features of the comorbidity.

Abstract: Summary: Purpose: The aim of this study was to evaluate the rate and features of obstructive sleep apnea (OSA) in adult epilepsy patients. Methods: Two hundred eighty-three adult epilepsy patients (137 men; mean age, 33 years; range, 18‐70 years) were prospectively screened for OSA by means of a structured interview. Those in whom OSA was clinically suspected were monitored for a full night by using a portable device (Polymesam), and OSA was diagnosed when they had an Apnea/Hypopnea Index greater than five. Results: Coexistence of OSA with epilepsy was found in 10.2% (15.4% of the male and 5.4% of the female) epilepsy patients investigated. The OSA was mild in 66.6%, moderate in 22.2%, and severe in 11.1% of the cases. The “epilepsy + OSA” patients were older, heavier, more frequently male, and sleepier (p < 0.05) than those with “epilepsy only.” Furthermore, they experienced their first seizure at an older age (p < 0.05). Conclusions: Systematic investigation reveals that OSA is frequent in epilepsy patients. The major risk factors for OSA in our epilepsy patients were the same as those typically found in the general population. Of the epilepsy-related factors, older age at onset of seizures appears to be significantly related to comorbidity with OSA (p < 0.05). The presence in epilepsy patients of these features should alert the clinician to the possibility of an underlying OSA. Key Words: Epilepsy—Obstructive sleep apnea.

Effects of valproate, phenobarbital, and carbamazepine on sex steroid setup in women with epilepsy.

Abstract: Serum levels of sex-hormones, sex-hormone binding globulin, gonadotropin, and prolactin were evaluated during the follicular and the luteal phases in 65 women with epilepsy and in 20 healthy controls. Twenty-one patients were treated with sodium valproate (VPA), 21 with phenobarbital (PB), and 23 with carbamazepine (CBZ). VPA does not stimulate liver microsome enzymes, whereas PB and CBZ do. Patients on VPA therapy showed higher body weight and body mass index, but no significant differences in hirsutism score, or in ovary volume or polycystic ovary prevalence (at ultrasound examination). Estradiol levels were lower in all patient groups than in healthy controls in the follicular but not in the luteal phases. VPA affected luteal progesterone surge in 63.6% of cases. This effect was significantly lower in the CBZ and PB groups. Furthermore, increases in testosterone and delta 4-androstenedione levels and in free androgen index, along with a higher luteinizing hormone-follicle-stimulating hormone ratio in the luteal phase, were observed in women treated with VPA. Although sex-hormone binding globulin levels were higher in CBZ and PB than in VPA-treated patients, the differences were not significant because of the wide dispersion of the carrier protein levels. Inducer antiepileptic drugs decreased dehydroepiandrosterone sulfate levels, which remained unchanged during VPA treatment. No significant differences occurred in basal gonadotropin and prolactin levels.

Menstrual cycle and ovary alterations in women with epilepsy on antiepileptic therapy

Abstract: Impaired reproductive function is thought to frequently affect women with epilepsy, mainly when seizures originate in the temporal lobe. In this study, we evaluated menstrual cycle features and assessed ovulation by determining luteal progesterone (Pg) levels in 101 consecutive women with epilepsy (36 with idiopathic generalized epilepsy -IGE; 65 with partial epilepsy -PE), aged between 16 and 50 years, treated with various antiepileptic drugs (AED). PE originated in the temporal lobe (TLE) in 40 subjects, in the frontal lobe in 13, in the parietal lobe in 2, while the origin of focal seizures remained undetermined in 10 patients. In all patients, menstrual and reproductive history, body mass index, hair distribution and hormonal pattern were assessed. Suprapubic ovary ultrasound (US) examination was carried out in 83 patients (28 with IGE, 55 with PE). Three patients with IGE and one with PE were amenorrheic. Oligomenorrhea occurred in 16 patients, polymenorrhea in 2. Changes in menstrual cyclicity were independent from epilepsy type (19.4% in IGE; 23.1% in PE) and from origin of focal discharges (22.5% of patients with TLE; 20.0% with origin in other brain areas). Luteal Pg levels remained below 2 ng/ml in 30 patients independently of epilepsy type. Corpus luteum dysfunction was combined with hyperandrogenism in 15 of these patients. In the other cases different alterations of hypothalamus-pituitary-ovary axis were observed. Valproic acid blunted luteal Pg surge more frequently than other AED. Polycystic ovaries (PCO) were observed in 14 (16.9%) patients (21.0% with IGE; 14.5% with PE). These prevalences are not higher than those reported in the general population. Among PE patients, PCO was found in 1 case with undertemined focal origin and in 7 TLE cases, who also had ovary volume significantly larger than patients with seizures originating from the frontal or parietal lobe. Epileptic women exhibited an increased occurrence of multifollicular ovaries (MFO) found in 12 cases (14.4% vs 5% in the general population). However, no defined hormonal or clinical pictures were associated with this US alteration in most patients. These findings reappraise the impact of ovary alterations in women mainly affected by mild to moderate epilepsy, on differing AED regimens, with the exception of more frequent ovulatory dysfunction and PCO occurrence in patients taking VPA.

Vigabatrin in the treatment of epilepsy: a double-blind, placebo-controlled study.

Abstract: Summary: The efficacy and tolerability of vigabatrin (γ-vinyl GABA, GVG), given as add-on therapy to 23 adult outpatients with severe drug-resistant epilepsy (17 with partial seizures), were studied using a double-blind, placebo-controlled, crossover design The study consisted of two 7-week periods during which vigabatrin and placebo were administered in random sequence Dosage was 10 g twice daily for patients weighing ≤65 kg and 15 g twice daily for patients weighing >65 kg Three patients were dropped from the study, two for reasons unrelated to treatment and one because of the appearance of vertigo, headache, dysarthria, and ataxia, which subsided rapidly when vigabatrin was stopped (3 g daily) Sixteen of the 20 patients available for analysis showed a decrease in the total number of seizures as compared with the placebo period Of these, 12 showed a >50% reduction in seizure frequency and 4 of the 12 showed a >75% reduction Both the total number of seizures and the number of partial seizures were significantly reduced by vigabatrin (p < 001) Only in the patient who dropped out were severe adverse effects seen The most frequently reported unwanted effect was mild drowsiness, which developed in seven patients on vigabatrin and in one on placebo Postitive effects, however, were also seen with six patients who reported an improved sense of well-being while receiving vigabatrin as compared with only 1 during the placebo period No consistent changes in electrocardiogram (ECG), electroencephalogram (EEG), and visual-, auditory-, and somatosensory-evoked potentials were seen during the study Serum levels of associated anticonvulsants remained unchanged, with the exception of a decrease in serum phe-nytoin during vigabatrin in the only phenytoin-treated patient We conclude that add-on treatment with vigabatrin is effective and well tolerated in adult patients with drug-resistant epilepsy RESUME L'efficacite et la tolerance du vigabatrin (gamma-vinyl-GABA, GVG) prescrit en supplement chez 23 patients adultes ambulatoires presentant une epilepsie severe et resistante (dont 17 avec des crises partielles), ont eteetudiees dans le cadre d'un protocole en double aveugle, contre placebo, avec cross-over L'etude a comporte 2 periodes de 7 semaines pendant lesquelles le GVG et le placebo ont ete administres dans un ordre laisse au hasard La dose etait de 1 g 2 fois par jour pour les patients pesant 65 kg ou moins, 1,5 g 2 fois par jour pour les patients pesant plus de 65 kg 3 patients ont abandonne l'etude, 2 pour des motifs sans liens avec le traitement, 1 en raison de l'apparition de vertiges, cephalees, dysarthrie et ataxie, rapidement resolutifs a l'arret du vigabatrin (3 g/j) 16 des 20 patients retenus ont presente une reduction de la frequence des crises par rapport a la periode placebo, dont 12 une reduction de plus de 50% et parmi ceux-ci, 4 une reduction de plus de 75% Le nombre total des crises et le nombre des crises partielles ont significativement diminue sous vigabatrin (p < 001) En dehors du patient qui a quitte l'etude, aucun effet secondaire serieux n'a ete note L'effet secondaire le plus frequemment rapporte fut une discrete somnolence, chez 7 patients sous vigabatrin et 1 patient sous placebo Des effets positifs ont cependant aussi ete signales par 6 patients sous vigabatrin qui ont note une sensation de mieux-etre, contre 1 patient sous placebo Il n'a pas ete note pendant cette etude de modification notable de l'ECG, de l'EEG ni des potentiels evoques visuels, auditifs ou somesthesiques Les taux seriques des anticomitiaux associes sont restes stables, a l'exception d'une diminution du taux sanguin de phenytoine pendant la periode GVG chez le seul patient recevant ce traitement Nous concluons que l'adjonction au traitement antiepileptique du vigabatrin est efficace et bien toleree chez les patients adultes presentant une epilepsie resistante aux therapeutiques RESUMEN Utilizando un estudio doble ciego, controlado con placebo y cruzado, se ha valorado la eficacia y tolerabilidad de la vigaba-trina (gamma-vinil-GABA, GVG), administrada como terapeutica complementaria a 23 pacientes adultos no hospitalizados con epilepsia severa resistente a medicaciones (17 de ellos con crisis parciales) El estudio consistio en dos periodos de siete semanas durante los cuales se administraron en una secuencia randomizada la vigabatrina y el placebo La dosis fue de 10 g dos veces diarias para pacientes que pesaban menos de 65 kg y 15 g dos veces diarias para pacientes por encima de los 65 kg Tres pacientes interrumpieron el estudio, 2 por razones no rela-cionadas con el tratamiento y 1 porque presento vertigos, dolor de cabeza, disartria y ataxia, sintomas que cesaron rapidamente al interrumpir la vigabatrina (3 g diarios) Dieciseis de los 20 pacientes disponibles para analisis mostraron una reduccion en el numero total de ataques comparandolos con el periodo de placebo De estos, 12 mostraron una reduccion por encima del 50% de la frecuencia de ataques y 4 de los 12 por encima del 75% Tanto el numero total de ataques como el numero de los ataques parciales se redujo significativamente con la vigabatrina (p < 001) Excluyendo el enfermo que abandono el estudio, no se observaron efectos adversos severos Las quejas mas frecuentes consistfan en ligera somnolencia que aparecio en 7 enfermos to-mando vigabatrina y en 1 con placebo Los efectos positivos, sin embargo, tambien fueron observados en 6 enfermos que decla-raban una mejorfa de su bienestar durante el tratamiento con vigabatrina comparandolos con solo 1 durante el periodo placebo No se observaron cambios persistentes en el ECG, EEG y en los potenciales evocados visuales, auditivos y somatosenso-riales durante el estudio Los niveles sericos de las medicaciones anticonvulsivas asociadas permanecieron sin modificacion con la excepcion de una reduccion de la fenitofna serica durante el tratamiento con vigabatrina y en el unico paciente tratado con enitoina Se concluye que el tratamiento complementario con vigabatrina es efectivo y bien tolerado en pacientes adultos con epilepsia resistente a medicaciones ZUSAMMENFASSUNG Die Wirkung von Vigabatrin (Gammavinyl Gaba, GVG) und die Toleranz ihm gegenuber wurde bei 23 erwachsenen ambu-lanten Patienten mit schwerer medikamentenresistenter Epilepsie (17 mit Partialanfallen) in einer Doppelblind- placebokon-trollierten Crossoverstudie untersucht, denen das Medikament zusatzlich gegeben wurde Die Untersuchung bestand aus zwei 7-Wochen-Perioden, wahrend welcher Vigabatrin und Placebo in Zufallsfolge angewandt wurden Die Dosierung betrug bei Patienten die 65 kg oder weniger wogen, 1 g 2 × taglich und fur Patienten iiber 65 kg 2 × taglich 1,5 g 3 Patienten schieden aus, 2 aus behandlungsunabhangigen Grilnden, 1 wegen Schwindel-zustanden, Kopfschmerzen, Dysarthrie und Ataxie die prompt auf Absetzen von Vigabatrin (3 g taglich) verschwanden 16 der 20 Patienten, die analysiert werden konnten, zeigten eine Ab-nahme der Anfallshaufigkeit verglichen mit der Placeboperiode Von diesen hatten 12 eine mehr als 50%-ige Verminderung der Anfallsfrequenz und 4 der 12 eine mehr als 75%-ige Sowohl die Gesamtzahl der Anfalle als auch die Anzahl der Partialanfalle wurden durch Vigabatrin signifikant reduziert (p < 0,01) Mit Ausnahme der Patienten, die ausschieden, wurden keine schweren Nebenwirkungen gesehen Der am haufigsten berich-tete unerwenschte Effekt war eine leichte Mudigkeit, die sich bei 7 Patienten unter Vigabatrin und bei 1 unter Placebo einstellte Positive Wirkungen wurden jedoch auch bei 6 Patienten gesehen, die ein gesteigertes Wohlbefinden unter Vigabatrin be-richteten Dem gegenuber steht nur 1 Patient, der solches wahrend der Placebo-Periode berichtete Keine deutlichen Veranderungen im EKG, EEG und in den VEP, AEP oder SSEP registriert wurden wahrend der Untersuchung Die Serumspiegel der anderen Antikonvulsiva anderten sich nicht; eine Ausnahme bildete die Abnahme des Serumphenytoin unter Vigabatrin beim einzigen mit Phenytoin behandelten Patienten Es wird gefol-gert, daβ die zusatzliche Therapie mit Vigabatrin wirkungsvoll ist und bei erwachsenen Patienten mit therapieresistenter Epilepsie gut vertragen wird

Patients with psychogenic nonepileptic seizures, alone or epilepsy-associated, share a psychological profile distinct from that of epilepsy patients

Abstract: The aim of this study was twofold: 1 – to identify a psychological profile of patients with psychogenic nonepileptic seizures (PNESs) that is possibly distinct from that of subjects affected by epileptic seizures (ESs) alone; 2 – to detect the possible differences between the clinical features and psychological profile of patients affected by PNESs alone and those of subjects in whom PNESs are associated with epileptic seizures (ES/PNES patients). We assessed the psychological profiles of 2 different groups of subjects. The first group was of 38 patients who had all developed PNESs after epileptic seizures (ES\PNES, group 1). The second group was of 31 patients with PNESs alone (PNES, group 2). We compared the psychological findings of each of these 2 groups with those of 2 control groups, composed of patients who matched groups 1 and 2 for sex, age, and educational level, but who were affected only by ESs (groups 1C and 2C). Finally, we considered possible differences between the ictal symptoms and signs of PNESs occurring in ES/PNES and in PNES patients. Both the ES/PNES group and the PNES group revealed higher percentages of Somatoform Disorders and Cluster B Personality Disorders (DSM-III-R diagnoses) than the ES patients in the control groups. The scores obtained on the Psychophysiological Distress Scale of the Cognitive Behavioural Assessment Battery (CBA) followed the same pattern. Among PNES ictal phenomena, autonomic symptoms and signs were significantly more frequent in the PNES than in the ES/PNES group. The occurrence of PNESs mimicking generalised tonic-clonic ESs (GTC-PNESs) was significantly associated with a low academic level. The results of this study suggest that the patients with PNESs alone and those affected by PNESs and ESs share the same psychological profile, which is different from that of patients with ESs alone. However, some differences between ES/PNES and PNES patients were found in the clinical semiology of their PNESs. Our findings could have implications for the diagnosis and for the treatment of patients with PNESs.

The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias.

Abstract: Context Narcolepsy, a neurological disorder affecting 1 in 2000 individuals, is associated with HLA-DQB1*0602 and low cerebrospinal fluid (CSF) hypocretin (orexin) levels. Objectives To delineate the spectrum of the hypocretin deficiency syndrome and to establish CSF hypocretin-1 measurements as a diagnostic tool for narcolepsy. Design Diagnosis, HLA-DQ, clinical data, the multiple sleep latency test (MSLT), and CSF hypocretin-1 were studied in a case series of patients with sleep disorders from 1999 to 2002. Signal detection analysis was used to determine the CSF hypocretin-1 levels best predictive for International Classification of Sleep Disorders (ICSD)–defined narcolepsy (blinded criterion standard). Clinical and demographic features were compared in narcoleptic subjects with and without low CSF hypocretin-1 levels. Setting Sleep disorder and neurology clinics in the United States and Europe, with biological testing performed at Stanford University, Stanford, Calif. Participants There were 274 patients with narcolepsy; hypersomnia; obstructive sleep apnea; restless legs syndrome; insomnia; and atypical hypersomnia cases such as familial cases, narcolepsy without cataplexy or without HLA-DQB1*0602, recurrent hypersomnias, and symptomatic cases (eg, Parkinson disease, depression, Prader-Willi syndrome, Niemann-Pick disease type C). The subject group also included 296 controls (healthy and with neurological disorders). Intervention Venopuncture for HLA typing, lumbar puncture for CSF analysis, primary diagnosis using the International Classification of Sleep Disorders, Stanford Sleep Inventory for evaluation of narcolepsy, and sleep recording studies. Main Outcome Measures Diagnostic threshold for CSF hypocretin-1, HLA-DQB1*0602 positivity, and clinical and polysomnographic features. Results HLA-DQB1*0602 frequency was increased in narcolepsy with typical cataplexy (93% vs 17% in controls), narcolepsy without cataplexy (56%), and in essential hypersomnia (52%). Hypocretin-1 levels below 110 pg/mL were diagnostic for narcolepsy. Values above 200 pg/mL were considered normal. Most subjects with low levels were HLA-DQB1*0602–positive narcolepsy-cataplexy patients. These patients did not always have abnormal MSLT. Rare subjects without cataplexy, DQB1*0602, and/or with secondary narcolepsy had low levels. Ten subjects with hypersomnia had intermediate levels, 7 with narcolepsy (often HLA negative, of secondary nature, and/or with atypical cataplexy or no cataplexy), and 1 with periodic hypersomnia. Healthy controls and subjects with other sleep disorders all had normal levels. Neurological subjects had generally normal levels (n = 194). Intermediate (n = 30) and low (n = 3) levels were observed in various acute neuropathologic conditions. Conclusions Narcolepsy-cataplexy with hypocretin deficiency is a genuine disease entity. Measuring CSF hypocretin-1 is a definitive diagnostic test, provided that it is interpreted within the clinical context. It may be most useful in cases with cataplexy and when the MSLT is difficult to interpret (ie, in subjects already treated with psychoactive drugs or with other concurrent sleep disorders).

Derivation of Research Diagnostic Criteria for Insomnia: Report of an American Academy of Sleep Medicine Work Group

Abstract: Insomnia is a highly prevalent, often debilitating, and economically burdensome form of sleep disturbance caused by various situational, medical, emotional, environmental and behavioral factors. Although several consensually-derived nosologies have described numerous insomnia phenotypes, research concerning these phenotypes has been greatly hampered by a lack of widely accepted operational research diagnostic criteria (RDC) for their definition. The lack of RDC has, in turn, led to inconsistent research findings for most phenotypes largely due to the variable definitions used for their ascertainment. Given this problem, the American Academy of Sleep Medicine (AASM) commissioned a Work Group (WG) to review the literature and identify those insomnia phenotypes that appear most valid and tenable. In addition, this WG was asked to derive standardized RDC for these phenotypes and recommend assessment procedures for their ascertainment. This report outlines the WG's findings, the insomnia RDC derived, and research assessment procedures the WG recommends for identifying study participants who meet these RDC.

Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease

Abstract: REM sleep behaviour disorder (RBD) is a parasomnia characterized by the loss of normal skeletal muscle atonia during REM sleep with prominent motor activity accompanying dreaming. The terminology relating to RBD, and mechanisms underlying REM sleep without atonia and RBD based on data in cat and rat are presented. Neuroimaging data from the few published human cases with RBD associated with structural lesions in the brainstem are presented, in which the dorsal midbrain and pons are implicated. Pharmacological manipulations which alter RBD frequency and severity are reviewed, and the data from human neuropathological studies are presented. An anatomic framework and new schema for the pathophysiology of RBD are proposed based on recent data in rat regarding the putative flip-flop switch for REM sleep control. The structure in man analogous to the subcoeruleus region in cat and sublaterodorsal nucleus in rat is proposed as the nucleus (and its associated efferent and afferent pathways) crucial to RBD pathophysiology. The association of RBD with neurological disease ('secondary RBD') is presented, with emphasis on RBD associated with neurodegenerative disease, particularly the synucleinopathies. The hypothesized pathophysiology of RBD is presented in relation to the Braak staging system for Parkinson's disease, in which the topography and temporal sequence of synuclein pathology in the brain could explain the evolution of parkinsonism and/or dementia well after the onset of RBD. These data suggest that many patients with 'idiopathic' RBD are actually exhibiting an early clinical manifestation of an evolving neurodegenerative disorder. Such patients may be appropriate for future drug therapies that affect synuclein pathophysiology, in which the development of parkinsonism and/or dementia could be delayed or prevented. We suggest that additional clinicopathological studies be performed in patients with dementia or parkinsonism, with and without RBD, as well as in patients with idiopathic RBD, to further elucidate the pathophysiology and also characterize the clinical and pathophysiological relevance of RBD in neurodegenerative disease. Furthermore, longitudinal studies in patients with idiopathic RBD are warranted to characterize the natural history of such patients and prepare for future therapeutic trials.

Epilepsy in Children

Abstract: 10·5 million children worldwide are estimated to have active epilepsy. Over the past 15 years, syndrome-oriented clinical and EEG diagnosis, and better aetiological diagnosis, especially supported by neuroimaging, has helped to clarify the diversity of epilepsy in children, and has improved management. Perinatal and postinfective encephalopathy, cortical dysplasia, and hippocampal sclerosis account for the most severe symptomatic epilepsies. Ion channel defects can underlie both benign age-related disorders and severe epileptic encephalopathies with a progressive disturbance in cerebral function. However, the reasons for age-related expression in children are not understood. Neither are the mechanisms whereby an epileptic encephalopathy originates. Several new drugs have been recently introduced but have provided limited therapeutic benefits. However, treatment and quality of life have improved because the syndrome-specific efficacy profile of drugs is better known, and there is heightened awareness that compounds with severe cognitive side-effects and heavy polytherapies should be avoided. Epilepsy surgery is an important option for a few well-selected individuals, but should be considered with great caution when there is no apparent underlying brain lesion.