A. Tartara

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

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.

Obstructive Sleep Apnea in a Clinical Series of Adult Epilepsy Patients: Frequency and Features of the Comorbidity

Summary:  Purpose: The aim of this study was to evaluate the rate and features of obstructive sleep apnea (OSA) in adult epilepsy patients.

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

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 1.0 g twice daily for patients weighing ≤65 kg and 1.5 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 < 0.01). 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.

Poor sleep in adolescents: A study of 869 17-year-old Italian secondary school students

Subjective sleep quality and its related factors were investigated in 869 (530 F, 339 M) 17‐year‐old adolescents, who were selected from the pupils of state‐run secondary schools in the city of Pavia in the north west of Italy. The study was conducted cross sectionally, and it consisted of a questionnaire based survey. One hundred and forty‐two subjects (16.5% of the whole sample, 19% of the females and 11.7% of the males) met the criteria chosen for definition as poor sleepers (namely, a complaint of «non restorative nocturnal sleep», «often» or «always» over the previous 12 mo). A significant association was found between chronic poor sleep and (1) gender (female) (2) emotional factors, such as worries, anxiety and depression (3) poor sleep hygiene (4) arousal related parasomnia. Only 4% of poor sleepers took sleep promoting drugs (including benzodiazepines, homeopathic products and other medications), generally without seeking medical advice.

Hypersomnia in the Prader Willi syndrome: clinical-electrophysiological features and underlying factors

OBJECTIVE Excessive daytime sleepiness is a common symptom in Prader Willi syndrome (PWs). Sleep disordered breathing (SDB) and narcoleptic traits such as REM sleep onsets (SOREMPs) have been reported in these subjects. We evaluated nighttime and daytime sleep patterns in patients with PWs in order to clarify the nature of their hypersomnia. DESIGN AND METHODS We performed overnight continuous EEG-polysomnographic studies (with breathing monitoring included) in 14 subjects (6 M,8 F; mean age 17 years, range 8-37) affected by PWs unselected for sleep disturbances. Ten patients underwent a Multiple Sleep Latency Test (MSLT) the day following the nocturnal sleep studies. Patients assessment was completed by means of immunogenetic characterization. RESULTS Nocturnal polysomnographic investigation documented sleep related breathing abnormalities such as central apneas, hypopneas or hypoventilation which mainly occurred during REM sleep in 8 subjects and did not cause sleep disruption. Only 4 subjects presented an increase in the Respiratory Disorder Index (RDI) slightly above the normal limits. In 8 subjects out of 10, with and without SDB, the mean daytime sleep latency could be considered abnormal according to the Tanner staging of pubertal development. Five patients showed at least two SOREMPs at MSLT. Subjects with and without SOREMPs had, respectively, a mean age of 18.6 SD 7.9 (4 M, 1 F) and 14.5 SD 2.9 (4 F, 1 M). The paternal deletion:uniparental dysomy ratio at genotypic characterization was 4:1 and 3.5:1 in subjects with and without SOREMPs, respectively. No patient presented DR-15 nor Dq-6. CONCLUSIONS Excessive sleepiness is a frequent disturbance in PWs. Subgroups of PW patients show hypersomnolence and SOREMPs. Sleep disordered breathing appears to have a limited role in the genesis of hypersomnia which not seems on the other hand attributable to the coexistence of narcolepsy phenotype. Hypersomnia in PW syndrome is likely to mainly be attributable to a primary hypothalamic dysfunction. The potential interacting role of other factors such as subjects age, sex and genetic pattern is suggested and deserve further investigation.

Sex Hormones and Pituitary Function in Male Epileptic Patients with Altered or Normal Sexuality

Summary Male epileptic patients frequently complain of sexual dysfunction, particularly impotence and loss of libido. Epilepsy itself, antiepileptic drugs (AEDs), and psychosocial factors are believed to contribute to impaired sexuality. We studied luteinizing hormone (LH) ulsatile secretion, gonadotropin, and prolactin (PRL) esponses to LH‐releasing hormone (LHRH) and thyrotropin‐releasing hormone (TRH) in 37 adult male epileptic patients receiving AED monotherapy who were seizure‐free and had normal EEGs. Sexuality was assessed by psychological interview. Impotence was diagnosed in 8 patients (in 2 combined with loss of sexual desire). The occurrence of hyposexuality (‐20%) was independent of epilepsy syndrome or AED. No change in total testosterone (T) level was observed. Free T (ft)and dihydrotestosterone (DHT) levels were lower and sex hormone binding globulin (SHBG) levels were higher in epileptic subjects than in healthy controls, but a statistically significant difference was not observed between hypo‐ and normosexual patients. In impotent epileptic patients, estradiol (E2) levels were significantly increased as compared with those of patients with preserved sexuality and of healthy controls. The unbalanced relation between androgen and E2 levels was emphasized by decreased fT/E2, fT/E2, and DHT/E2 ratios obtained in hyposexual epileptic patients. In this group, LHRH induced blunted LH peaks. No changes were noted in LH pulsatility features. These findings of higher E2 levels and of decreased LH response to LHRH administration in some epileptic patients with impaired sexuality, may suggest they have subclinical hypogonadotropic hypogonadism.

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.

Partial Epileptic Seizures of Different Origin Variably Affect Cardiac Rhythm

Summary: Purpose: The present study was aimed at evaluating electrocardiographic (ECG) changes associated with partial epileptic seizures without seizure activity secondarily generalized.

Evaluation of sleepiness in epilepsy

Excessive daytime sleepiness often complicates the clinical picture of epilepsy, facilitating the occurrence of seizures and aggravating cognitive disabilities and/or behavioral problems. Thus it further adversely affects social and working activities of epileptic subjects. Both unstructured and structured clinical reports documented a not negligible proportion of epilepsy patients suffering from excessive daytime sleepiness. Studies based on neurophysiological testing such as Multiple Sleep Latency Test or Maintenance Wakefulness Test revealed a degree of daytime sleepiness tendency in epilepsy patients greater than that they subjectively estimate. Antiepileptic drugs play a remarkable role in determining drowsiness in epilepsy patients and they are generally viewed as the only cause of sleepiness in these patients. However excessive daytime sleepiness has been documented in epilepsy patients before starting any drug treatment or after its discontinuation. Both clinical and neurophysiological studies have clearly documented the possible role of seizure occurrence and of co-morbidity as determinants of excessive daytime sleepiness in epilepsy patients. Nocturnal sleep fragmentation and daytime sleepiness have been reported in temporal lobe and frontal lobe epilepsy, namely nocturnal frontal lobe epilepsy. Some recent reports have stressed that obstructive sleep apnea and periodic limb movements during sleep can significantly account for sleepiness complaints in epilepsy patients; most of the antiepileptic drugs can worsen obstructive sleep apnea. To date the evaluation of daytime sleepiness of epilepsy patients in clinical practice has been based mainly or exclusively on clinical reports. To improve our understanding of this symptom in epilepsy patients, the use of standardized sleepiness scales should be encouraged. Patients with persistent daytime sleepiness without a clear cause-and-effect relationship with antiepiletic drugs treatment or in whom a coincident sleep pathology is suspected, should be investigated by means of neurophysiological testing such as Multiple Sleep Latency Test or Maintenance Wakefulness Test.

Nocturnal sleep in multisystem atrophy with autonomic failure: Polygraphic findings in ten patients

A nocturnal polysomnographic study with infrared video-monitoring was performed in ten patients with multisystem atrophy with autonomic failure (MSA-AF) (seven males, three females; median age: 54 years), selected irrespective of the presence of sleep complaints. The MSA-AF patients showed disrupted sleep patterns. Quantitative and qualitative alterations of REM sleep were found, some of which resembled those seen in patients with REM sleep behaviour syndrome. However, only one patient reported episodes of REM behaviour. Six patients showed arterial oxyhaemoglobin (HbSaO2) drops below 90% during sleep in relation to recurrent apnoeas or hypopnoeas (HbSaO2 nadir 70%). The apnoea hypopnoea index was above the upper limit of the normal range in three of these patients in the absence of obesity or bronchopulmonary diseases. Among patients with sleep-related breathing impairment, laryngeal stridor (three cases) or snoring (one case) were observed. Patients with sleep-related breathing disorders (SBD) exhibited a higher degree of autonomic dysfunction than patients without SBD.