Sleep macrostructure and cyclic alternating pattern in patients who underwent surgery for hippocampal sclerosis: A prospective controlled polysomnographic study.

INTRODUCTION: Temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS) is one of the most common drug-resistant epilepsy. Surgery is currently accepted as an effective and safe therapeutic approach compared to antiseizure medications (ASMs). The study aims to evaluate the effect of surgical treatment of TLE-HS on sleep profile and architecture by subjective and objective evaluation of sleep in basal condition after one month and one year. METHODS: Thirteen patients with TLE-HS were recruited to undergo overnight polysomnography and a subjective evaluation of nocturnal sleep utilizing the Pittsburgh Sleep Quality Index (PSQI) and daytime somnolence through the Epworth Sleepiness Scale (ESS) in basal condition (T0), one month (T1) and one year after surgery (T2), respectively. Thirteen healthy controls (HC) matched for age, sex and BMI were recruited. Scoring and analysis of sleep macrostructure and cyclic alternating pattern (CAP) parameters were performed. RESULTS: The comparison between patients in basal condition (T0) and HC showed a significant lower sleep efficiency (p = 0.003) and REM percentage (p < 0.001). Regarding CAP, patients at T0 showed higher total CAP rate (p < 0.001), CAP rate in N2 (p < 0.001), higher A3 (%) (p = 0.001), higher mean duration of A1 (p = 0.002), A3 index (p < 0.001), cycle in sequences (p < 0.001), lower B duration (p < 0.001), cycle mean duration (p < 0.001) than HC. Surgery did not induce significant changes in nocturnal macrostructural polysomnographic variables in T1 and T2. Lower CAP rate (T1 vs T0 and T2 vs T0 p < 0.001), CAP rate in N3 (T1 vs T0 and T2 vs T0 p < 0.001), A3 (%) (T1 vs T0 and T2 vs T0 p < 0.001); lower phase A2 index (T1 vs T0 p < 0.001) and A3 index (T1 vs T0 p < 0.001), lower phase A1 index (T2 vs T0 p < 0.001) and cycle in sequences (T2 vs T0 p = 0.002) higher B mean duration (T2 vs T0 p = 0.002). No significant differences were found between T1 and T2 in CAP parameters. CONCLUSION: We found a significant NREM sleep instability in patients with TLE-HS compared with HC. In addition, anterior temporal lobectomy (ATL) induced a significant improvement in sleep continuity as evaluated by cyclic alternating pattern already one month later and this effect persisted after one year. ALT seems to restore a more resilient sleeping brain.

Subjective sleep disorders and daytime sleepiness in patients with restrictive type anorexia nervosa and effects on quality of life: a case-control study.

To evaluate sleep disorders and daytime drowsiness in a cohort of patients affected by anorexia nervosa and their impact on health-related quality of life. We evaluated patients affected by restricting-type of anorexia nervosa (AN-R) and healthy controls by the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale, Beck Depression Index. We also used the Short-Form Health Survey (SF-36) questionnaire to assess the quality of life in both AN-R and controls. Twenty-eight out of 34 AN-R patients (82.3%) in contrast with ten out of 34 healthy subjects (29.4%) had a pathological PSQI score compared to HC (p < 0.0001). The overall PSQI score (p < 0.001), sleep quality (p < 0.001), sleep duration (p = 0.02), sleep efficiency (p = 0.002), sleep disturbances (p = 0.03) and daytime dysfunction (p = 0.004) were significantly higher in AN-R than in controls. SF36 showed significantly reduced scores of standardized physical components (p = 0.01) and standardized mental components (p < 0.001), physical function (p < 0.001), physical role (p < 0.001) and general health (p < 0.001), vitality (p < 0.001), social functioning (p < 0.001) emotional role (p = 0.001) and mental health (p < 0.001) in AN-R. We found a significant correlation between the PSQI score and both the physical role (r = - 0.35, p = 0.03) and level of education (r = 0.38, p = 0.02). Our data showed reduced overall sleep quality without excessive daytime sleepiness in AN-R. Sleep quality correlated significantly with quality of life (physical role) and level of education.

Sleep Disorders in Patients With Craniopharyngioma: A Physiopathological and Practical Update.

Sleep disorders (SDs) represent an important issue in patients with craniopharyngioma (CP). Nearly 70% of these patients complain of sleep-wake cycle alterations and/or excessive diurnal somnolence due to sleep-related breathing disorders, such as obstructive sleep apnea (OSA) and/or central hypersomnia, including secondary narcolepsy. SDs may severely reduce quality of life, increase disease-related cardiorespiratory and cardiovascular morbidity, and finally play a major role in increased long-term mortality reported on patients with CP. A major risk factor for SDs is represented by the hypothalamic syndrome, which may develop because of direct hypothalamic damage by the tumor itself and/or complications of the treatments, neurosurgery and/or radiotherapy, and typically includes permanent neuroendocrine dysfunctions, morbid obesity, and secondary metabolic disorders. Despite increasing attention to SDs in the general population, and in particular to OSA as a risk factor for cardio-metabolic diseases and excessive daytime somnolence, sleep evaluation is still not routinely proposed to patients with CP. Hence, SDs are often underdiagnosed and undertreated. The aim of this paper is to update current knowledge of the pathogenesis and prevalence of SDs in patients with CP and propose practical algorithms for their evaluation and management in clinical practice. Particular attention is paid to screening and diagnostic tools for appropriate characterization of SDs, identification of risk factors, and potential role of hypothalamic sparing surgery in the prevention of morbid obesity and SDs. Available tools in sleep medicine, including lifestyle interventions, drugs, and respiratory devices, are discussed, as well as the importance of optimal hormone replacement and metabolic interventions. Current limits in the diagnosis and treatment of SDs in patients with CP and possible future avenues for research agenda are also considered.

Effects of eslicarbazepine as add-on therapy on sleep architecture in temporal lobe epilepsy: results from "Esleep" study.

RATIONALE: Studies looking at the effect of antiseizure medications (ASMs) on the sleep microstructure of subjects with epilepsy are scarce. This study aims to evaluate the impact of eslicarbazepine (ESL) as add-on therapy on the sleep microstructure in temporal lobe epilepsy (TLE). METHODS: Twelve patients affected by TLE were recruited to undergo overnight polysomnography and a subjective evaluation of nocturnal sleep utilizing the Pittsburgh Sleep Quality Index (PSQI) and daytime somnolence through the Epworth Sleepiness Scale (ESS) before and after three months of treatment with ESL as add-on therapy. Ten healthy controls (HC) matched for age, sex and BMI were recruited. Scoring and analysis of sleep macrostructure and cyclic alternating pattern (CAP) parameters were performed. RESULTS: Ten patients completed the study. The comparison between patients in basal condition (T0) and HC showed a significant lower sleep efficiency (p = 0.049), REM percentage (p = 0.002), higher REM latency (p = 0.02), N2 (p = 0.001) and WASO (p = 0.01). Regarding CAP, patients at T0 showed higher CAP rate in N1 (p = 0.01), lower A1 (%) (p = 0.03), higher A3 (%) (p = 0.01), higher mean duration of A (p = 0.02) and A3 (p = 0.006), A3 index (p = 0.02) than HC. ESL did not induce any significant changes in nocturnal macrostructural polysomnographic variables and PSQI scores. Furthermore, the ESS score showed no modification after treatment. Lower CAP rate in N3 (p = 0.02), phase A2 index (p = 0.02) average number of CAP cycle per sequences and mean duration of CAP sequences (both p = 0.02) was evident after ESL. A trend toward significance was evident for the decrease of CAP rate in N1 (p = 0.09) and N2 (p = 0.09), and for the increase of B phase mean duration (p = 0.07). CONCLUSION: We found significant improvement in sleep continuity as measured by CAP after ESL. These findings suggest that ESL may positively modulate sleep fragmentation in patients with TLE, and hence enhance sleep quality. Our results suggest a favourable sleep profile with the use of ESL.

Sleep Complaints, Sleep and Breathing Disorders in Myotonic Dystrophy Type 2.

PURPOSE OF REVIEW: To update the current knowledge concerning sleep complaints and breathing disorders in myotonic dystrophy type 2 (DM2) and to better understand if sleep and breathing symptoms may add a further clinical definition of DM2. RECENT FINDINGS: Although DM2 has been poorly evaluated, the most relevant sleep disorders are sleep-disordered breathing (SDB) (37.5-66.7%) and restless legs syndrome (RLS) (50-60%). Excessive daytime somnolence (EDS) is not consistent with SDB, and a large percentage of patients with sleep complaints (58-69%) report pain. In addition, respiratory dysfunctions are reported in 6 to 15% of DM2 patients, albeit few data are available regarding pulmonary restriction, hypoventilation, and non-invasive ventilation (NIV). SDB, RLS, and pain may contribute to sleep fragmentation and EDS in DM2. In addition, few studies report hypoventilation and pulmonary restriction, although there are no studies at all on NIV, except for limited clinical experiences. These findings suggest performing a careful pulmonary examination and NIV when required. Furthermore, sleep studies and respiratory evaluation should be recommended if OSA or respiratory muscle dysfunctions are suspected. A large polysomnographic study should be performed to clarify the link between sleep disorders, pain, and sleep disruption in DM2.

Comparative Sleep Disturbances in Myotonic Dystrophy Types 1 and 2.

PURPOSE OF REVIEW: To update current knowledge regarding sleep disturbances and myotonic dystrophies so as to better understand if sleep symptoms may help in the early recognition of the two genetic subtypes: myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2). RECENT FINDINGS: Sleep-disordered breathing (SDB), restless legs syndrome, periodic limb movements in sleep, hypersomnia, and REM sleep dysregulation are frequently described in DM1 patients. SDB does not always explain hypersomnia, but a central dysregulation of sleep-wake modulation is reported mainly in DM1. Sleep apnea, restless legs syndrome, and REM sleep without atonia have been reported in single case reports and small case series of DM2. DM2 is less prevalent and more recently described than DM1, with a milder phenotype than DM1. The most frequent sleep disorders in DM1 are hypersomnia, SDB, periodic limb movements, and a narcoleptic-like phenotype, whereas restless legs syndrome, SDB, and REM sleep without atonia seem to be the most frequent sleep disorders in DM2. Comparative sleep studies are strongly required to delineate the sleep phenotype of myotonic dystrophies.

Profile of pitolisant in the management of narcolepsy: design, development, and place in therapy.

Narcolepsy is a rare sleep disorder characterized by excessive daytime sleepiness and rapid eye movement sleep dysregulation, manifesting as cataplexy and sleep paralysis, as well as hypnagogic and hypnopompic hallucinations. Disease onset may occur at any age, although adolescents and young adults are mainly affected. Currently, the diagnosis delay ranges from 8 to 10 years and drug therapy may only attenuate symptoms. Pitolisant is a first-in-class new drug currently authorized by the European Medicines Agency to treat narcolepsy with or without cataplexy in adults and with an expanded evaluation for the treatment of neurologic diseases such as Parkinson's disease and epilepsy. This article reviews the pharmacokinetic and pharmacodynamic profile of pitolisant, highlighting its effectiveness and safety in patients with narcolepsy. We performed a systematic review of the literature using PubMed, Embase, and Google Scholar. We report on the efficacy and safety data of pitolisant in narcoleptic patients regarding cataplexy episodes and subjective and objective daytime sleepiness. The development program of pitolisant was characterized by eight Phase II/III studies. One proof-of-concept study followed by two pivotal studies, three randomized controlled trials, and two open studies were evaluated. Our review confirmed the effectiveness of pitolisant in treating major clinically relevant narcolepsy symptoms, including cataplexy, as compared to placebo. In addition, pitolisant revealed a safe profile when compared with placebo and active comparators. Headache, insomnia, and nausea were the prominent side effects. Further long-term randomized controlled trials comparing the efficacy of pitolisant with active comparators (ie, modafinil and sodium oxybate) may clarify its real place in therapy and its possible use as a first-line agent on the basis of its safety and tolerability.

Zonisamide in the management of epilepsy in the elderly.

Zonisamide (ZNS), a second-generation antiepileptic drug, indicated as add-on treatment of focal epilepsy, has been recently approved as monotherapy for the treatment of partial seizures in adults affected by newly diagnosed epilepsy in Europe. Evidence on the efficacy and tolerability of antiepileptic drugs in the elderly is still lacking as these patients are frequently excluded from clinical trials. Here, a comprehensive overview of available data regarding the use of ZNS in the treatment of epilepsy in elderly people is provided. In a pooled analysis conducted in patients aged ≥65 years, no new/unexpected safety findings have emerged. Few data from uncontrolled investigations suggest that ZNS may be effective and well tolerated when administered as monotherapy or adjunctive antiepileptic treatment in the elderly. However, evidence from these observational studies is less than satisfactory, and randomized controlled trials focused on these patients are still needed.

Topiramate-induced periodic limb movement disorder in a patient affected by focal epilepsy.

Periodic limb movement disorder (PLMD) is characterized by pathological periodic limb movements during sleep, insomnia and/or diurnal sleepiness, and the absence of another primary sleep disorder. We report a patient with complex partial seizures who developed PLMD while taking topiramate (TPM). He had no evidence of metabolic and/or other conditions inducing PLMD. He also had fragmented sleep and disruptive PLMS on polysomnography, and PLMS subsided with change of antiepileptic drug. Topiramate may modulate the dopaminergic pathway by inhibition of glutamate release, thereby inducing PLMD as observed in our patient. Although a single case does not allow any generalization, PLMD should be considered in patients complaining of insomnia and treated with TPM.

Improvement of restless legs syndrome by varenicline as antismoking treatment.

Varenicline is a partial agonist at the α4ß2 nicotinic acetylcholine receptor effective as smoking cessation pharmacotherapy. We present a familial case of severe restless legs syndrome (RLS) resistant to polytherapy who showed a consistent and effective amelioration of RLS symptoms after introduction of varenicline as antismoking drug.

Effects of zonisamide as add-on therapy on sleep-wake cycle in focal epilepsy: a polysomnographic study.

PURPOSE: The purpose of this study was to evaluate the effects of zonisamide (ZNS) as adjunctive therapy on sleep-wake cycle and daytime somnolence in adult patients affected by focal epilepsy. METHODS: Thirteen patients affected by focal epilepsy were recruited to undergo a 24-hour ambulatory polysomnography, Multiple Sleep Latency Test (MSLT), and a subjective evaluation of nocturnal sleep by means of the Pittsburgh Sleep Quality Index (PSQI) and daytime somnolence by means of the Epworth Sleepiness Scale (ESS) before and after 3 months of treatment with ZNS as add-on therapy. RESULTS: Twelve patients completed the study. Zonisamide therapy reduced seizures by >50% in 8 out of 12 patients. Zonisamide did not induce any significant changes in nocturnal polysomnographic variables and in PSQI scores. In addition, mean sleep latency and ESS score were unmodified after treatment. CONCLUSION: Zonisamide seems to be effective and safe in focal epilepsy. Both subjective and objective sleep parameters showed no detrimental effects on nocturnal sleep and daytime somnolence in patients with focal epilepsy using ZNS. Since some AEDs induce sleep impairment, which is known to trigger EEG abnormalities and seizures and to worsen quality of life, our findings suggest a positive profile of ZNS.