Raffaele Manni

Relationship between hallucinations, delusions, and rapid eye movement sleep behavior disorder in Parkinson's disease.

Psychotic symptoms are the main and the most disabling “nonmotor” complications of Parkinsons disease (PD), the pathophysiology of which is poorly recognized. Polysomnographic studies have shown a relationship between visual hallucinations and rapid eye movement (REM) sleep. The objective of this study is to clarify the relationship between psychotic symptoms and REM sleep behavior disorder (RBD) in PD. In a Parkinsons disease outpatient unit, 289 consecutive subjects with idiopathic PD were administered (in the period from January to December 2002) a multiple‐choice questionnaire and structured interview on sleep and mental disorders. RBD was diagnosed in accordance with the minimal diagnostic criteria of the International Classification of Sleep Disorders. Hallucinations and delusional disorders were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders‐IV criteria. The presence or absence of psychotic symptoms, of RBD, and of daytime sleepiness, as well as motor status, cognitive status, and mood were assessed. Approximately 32% (n = 92) of the subjects presented with psychotic disorders; 30% (n = 86) had experienced hallucinations; 2% (n = 6) had delusions without hallucinations. Sixty‐two (72%) hallucinators reported nocturnal hallucinations. A total of 6.6% (n = 19) of the subjects complained of a delusional disorder. There were 26.6% (n = 77) of subjects who presented with RBD: 28 (36%) with onset before and 49 (63%) with onset after PD diagnosis. The presence of RBD was associated with an increased risk of manifesting hallucinations and delusions (odds ratio [OR], 2.73). Other independent clinical factors found to have an effect on psychotic disorders were cognitive impairment (OR, 3.92), disease duration (OR, 2.46), advanced age (OR, 2.34), and severity of motor symptoms (OR, 2.06). These results suggest that RBD is widely associated with psychosis in PD.

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.

REM sleep behavior disorder, hallucinations, and cognitive impairment in Parkinson's disease

The objective of this study was to evaluate the relationship between REM sleep behavior disorder (RBD), hallucinations, and cognitive impairment in Parkinsons disease (PD). One hundred and ten PD patients, divided into three groups (without RBD or hallucinations; with RBD but no hallucinations; with RBD and hallucinations), were submitted to neuropsychological evaluation. The group without RBD and hallucinations showed normal neuropsychological tests when compared to normal controls. The group with hallucinations was characterized by a more severe cognitive impairment affecting both short‐ and long‐term memory, logical abilities, and frontal functions, while the RBD‐only group presented frontal impairment. The hypothesis that RBD in PD can be considered a risk factor not only of the hallucinations but also of more severe and diffuse cognitive abnormalities needs to be strengthened through a longitudinal evaluation.

Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: A multicenter study

To assess whether risk factors for Parkinson disease and dementia with Lewy bodies increase rate of defined neurodegenerative disease in idiopathic rapid eye movement (REM) sleep behavior disorder (RBD).

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.

Comorbidity between epilepsy and sleep disorders

Despite being relatively common and potentially able to have clinical and pathophysiological consequences, the comorbidity between epilepsy and sleep disorders is poorly investigated in the literature and rarely taken into consideration by clinicians in general practice. There is increasing evidence that obstructive sleep apnoea (OSA) coexists in epilepsy (in 10% of unselected adult epilepsy patients, 20% of children with epilepsy and up to 30% of drug-resistant epilepsy patients). A few lines of evidence suggest that continuous positive airway pressure treatment of OSA in epilepsy patients improves seizure control, cognitive performance and quality of life. Parasomnias and epileptic seizures can coexist in the same subject making the differential diagnosis of these conditions particularly challenging. In childhood, a frequent association between epilepsy and NREM arousal parasomnias, enuresis and rhythmic movement disorder has been documented. A particular pattern of association has been found between nocturnal frontal lobe epilepsy (NFLE) and NREM arousal parasomnias, the latter being found in the personal or family history of up to one third of NFLE patients. As far as REM parasomnias are concerned, REM sleep behaviour disorder, unrecognised or misdiagnosed, has been found to co-occur in 12% of elderly epilepsy patients. Patients with epilepsy often complain of poor, non-restorative sleep; however, insomnia in epilepsy is poorly investigated, with the literature giving conflicting prevalence data and no information on the impact of this disorder on seizure control, or on the best therapeutic approach to insomnia in this particular group of patients. A greater awareness, among clinicians, of the comorbidities between sleep disorders and epilepsy may help to prevent misdiagnosis and mistreatment. Sleep hygiene measures in epilepsy need to be more comprehensive, taking into account the various pathologies that may underlie disordered sleep in epilepsy patients.

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.

The FLEP scale in diagnosing nocturnal frontal lobe epilepsy, NREM and REM parasomnias: Data from a tertiary sleep and epilepsy unit

Purpose: To test the usefulness of the FLEP scale in diagnosing nocturnal frontal lobe epilepsy (NFLE), arousal parasomnias, and REM sleep behavior disorder (RBD).