Nocturnal frontal lobe epilepsy

The paroxysmal motor events during sleep are certainly common.The systematic use of nocturnal video-polysomnography has largely improved the diagnostic yield in patients with clusters of nocturnal motor events. Two broad nosological categories have been identified: parasomnias (sleep terror and sleep-walking), which are thought to represent disorders of arousal during sleep, and the epileptic seizures arising from sleep (nocturnal epilepsy). In recent years, particular attention has been devoted to those seizures arising from epileptic foci located within the frontal lobe or within the temporal lobe with early involvement of the frontal lobe: so-called nocturnal frontal lobe epilepsy (NFLE). Also in recent years the clinical, neuroradiological and neurophysiological profile of NFLE has clearly been delineated: up to 40% of patients with NFLE had at least one first-degree relative with a probable primary parasomnia: about 20% of patients had a family history of epilepsy; 5 to 10% had NFLE, with nocturnal seizures quite similar to those of the proband; the age at onset of seizures ranged from 1 to 65 years; the mean frequency of seizures was 15-20 per month; patients often complained of nocturnal sleep disruption (about one half of them reported excessive daytime sleepiness); one third of patients also had occasional seizures during wakefulness, usually in childhood; the seizures had a stereotypic motor pattern, of various complexity; traditional neuroradiological examinations showed abnormalities in about 10% of cases; there was a wide intra-familial variation in the severity of seizure disorder. There was also considerable intra-individual variation in severity during the different periods of life, with an age-dependent degree of severity; ictal EEG abnormalities were found in 30 to 60% of patients; the EEG during sleep showed interictal focal epileptiform abnormalities in about 50% of patients; in about two third of patients carbamazepine, clonazepam or their association were able to greatly reduce nocturnal seizures in frequency and complexity and, in some cases, to completely control them. The differential diagnosis between sporadic (and familial) NFLE from benign parasomnias is difficult from the history alone. A full video-polysomnographic study should be proposed to all the patients complaining of repeated nocturnal motor, autonomic and behavioural episodes, in order to provide a correct diagnosis

Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy

Narcolepsy has genetic and environmental risk factors, but the specific genetic risk loci and interaction with environmental triggers are not well understood. Here, the authors identify genetic loci for narcolepsy, suggesting infection as a trigger and dendritic and helper T cell involvement. Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix (R). Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix (R)

Parkinsonism with excessive daytime sleepiness: A narcolepsy-like disorder?

Abstract : Background : Parkinsonian patients with excessive daytime sleepiness (EDS), hallucinations, REM sleep behavior disorder (RBD), short mean sleep latencies, and sleep-onset REM periods (SOREMP) on multiple sleep latency tests (MSLT) have been reported. In these patients a narcolepsy-like pathophysiology of sleep-wake disturbances has been suggested. Patients and methods : We studied 14 consecutive patients with Parkinsonism and EDS. Standard studies included assessment of duration and severity of Parkinsonism (Hoehn & Yahr score), Epworth sleepiness score (ESS), history of "REM-symptoms” (RBD/hallucinations/sleep paralysis/cataplexy-like episodes), polysomnography (PSG),MSLT, and measurement of cerebrospinal fluid (CSF) levels of hypocretin-1 (orexin A). Results : There were 12 men and 2 women (mean age 69 years; range 54-82). The mean duration and the Hoehn & Yahr score were 6.3 years and 2.2, respectively. Diagnoses included idiopathic Parkinson's disease (IPD, n=10), dementia with diffuse Lewy bodies (n=3), and multisystem atrophy (n=1). The ESS was ≥10 in all patients (mean 12; range 10-18). "REM-symptoms” were reported by all but two patients (hallucinations: n=9; RBD: n=9).None of the patients reported cataplexy-like symptoms or sleep paralysis. On PSG sleep apnea (apnea hypopnea index > 10/h, n=7), periodic limb movements during sleep (PLMS-index > 10/h, n=6), and features of RBD (n=5) were found. On MSLT mean sleep latency was < 5 minutes in 10 patients, and SOREMP were found in two patients. When compared with controls (n=20, mean 497 pg/ml; range 350-603), CSF hypocretin-1 levels were normal in 8 patients and low in 2 patients (221 and 307 pg/ml, respectively). Conclusion : These findings do not support the hypothesis of a "final common pathway” in the pathophysiology of narcolepsy and Parkinsonism with EDS. Sleep apnea and PLMS may play a so-far underestimated role in the pathogenesis of EDS in Parkinsonian patient

Exploring depression in Alzheimer's disease: an Italian Delphi Consensus on phenomenology, diagnosis, and management

Background: In Alzheimer's disease (AD), the progressive cognitive impairment is often combined with a variety of neuropsychiatric symptoms, firstly depression. Nevertheless, its diagnosis and management is difficult, since specific diagnostic criteria and guidelines for treatment are still lacking. The aim of this Delphi study is to reach a shared point of view among different Italian specialists on depression in AD. Methods: An online Delphi survey with 30 questions regarding epidemiology, diagnosis, clinical features, and treatment of depression in AD was administered anonymously to a panel of 53 expert clinicians. Results: Consensus was achieved in most cases (86%). In the 80% of statements, a positive consensus was reached, while in 6% a negative consensus was achieved. No consensus was obtained in 14%. Among the most relevant findings, the link between depression and AD is believed to be strong and concerns etiopathogenesis and phenomenology. Further, depression in AD seems to have specific features compared to major depressive disorder (MDD). Regarding diagnosis, the DSM 5 diagnostic criteria for MDD seems to be not able to detect the specific aspects of depression in AD. Concerning treatment, antidepressant drugs are generally considered the main option for depression in dementia, according to previous guidelines. In order to limit side effects, multimodal and SSRI antidepressant are preferred by clinicians. In particular, the procognitive effect of vortioxetine seems to be appealing for the treatment of depression in AD. Conclusions: This study highlights some crucial aspects of depression in AD, but more investigations and specific recommendations are needed

Extreme sleep state misperception: From psychopathology to objective-subjective sleep measures

Study objectives: We tested the hypothesis that patients with extreme sleep state misperception display higher levels of psychopathology and reduced quantitative estimation abilities compared to other patients with insomnia. Secondary aims included the evaluation of group differences in subjective self-reported quality of life and sleep quality and objective sleep parameters. Methods: In this cross-sectional, observational study, 249 patients with insomnia underwent a video-polysomnography with a subsequent morning interview to assess self-reported sleep estimates and filled in a large battery of questionnaires. Patients were classified into High Misperception (HM) and Moderate Misperception (MM) groups, according to the complement of the ratio between self-reported total sleep time and objective total sleep time (Misperception Index). Results: No significant differences emerged in any of the psychopathological measures considered between the HM and the MM group. Similarly, no effect was observed in quantitative estimation abilities. HM patients displayed a significantly increased number of awakenings per hour of sleep and a reduced dream recall rate. Their overall sleep quality and quality of life was significantly impaired. Conclusions: Future research on sleep misperception should focus on factors other than the level of psychopathology and estimation abilities, in particular sleep microstructure and quantitative EEG studies in both REM and NREM slee

Metabolic connectivity of resting-state networks in alpha synucleinopathies, from prodromal to dementia phase

Previous evidence suggests that the derangement of large-scale brain networks reflects structural, molecular, and functional mechanisms underlying neurodegenerative diseases. Although the alterations of multiple large-scale brain networks in Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) are reported, a comprehensive study on connectivity reconfiguration starting from the preclinical phase is still lacking. We aimed to investigate shared and disease-specific changes in the large-scale networks across the Lewy Bodies (LB) disorders spectrum using a brain metabolic connectivity approach. We included 30 patients with isolated REM sleep behavior disorder (iRBD), 28 with stable PD, 30 with DLB, and 30 healthy controls for comparison. We applied seed-based interregional correlation analyses (IRCA) to evaluate the metabolic connectivity in the large-scale resting-state networks, as assessed by [18F]FDG-PET, in each clinical group compared to controls. We assessed metabolic connectivity changes by applying the IRCA and specific connectivity metrics, such as the weighted and unweighted Dice similarity coefficients (DC), for the topographical similarities. All the investigated large-scale brain resting-state networks showed metabolic connectivity alterations, supporting the widespread involvement of brain connectivity within the alpha-synuclein spectrum. Connectivity alterations were already evident in iRBD, severely affecting the posterior default mode, attentive and limbic networks. Strong similarities emerged in iRBD and DLB that showed comparable connectivity alterations in most large-scale networks, particularly in the posterior default mode and attentive networks. Contrarily, PD showed the main connectivity alterations limited to motor and somatosensory networks. The present findings reveal that metabolic connectivity alterations in the large-scale networks are already present in the early iRBD phase, resembling the DLB metabolic connectivity changes. This suggests and confirms iRBD as a risk condition for progression to the severe LB disease phenotype. Of note, the neurobiology of stable PD supports its more benign phenotype

Exploring depression in Parkinson's disease: an Italian Delphi Consensus on phenomenology, diagnosis, and management

Background: Depression is a prodromic and a frequent non-motor symptom of Parkinson's disease, associated to reduced quality of life and poor outcomes. The diagnosis of depression in parkinsonian patients represents a challenge due to the overlapping of symptoms typical of the two conditions. Methods: A Delphi panel survey was performed to reach a consensus amongst different Italian specialists on four main topics: the neuropathological correlates of depression, main clinical aspects, diagnosis, and management of depression in Parkinson's disease. Results and conclusion: Experts have recognized that depression is an established risk factor of PD and that its anatomic substrate is related to the neuropathological abnormalities typical of the disease. Multimodal and SSRI antidepressant have been confirmed as a valid therapeutic option in the treatment of depression in PD. Tolerability, safety profile, and potential efficacy on broad spectrum of symptoms of depression including cognitive symptoms and anhedonia should be considered when selecting an antidepressant and the choice should be tailored on the patients' characteristics

Executive Functioning and Personality Traits in Insomnia Disorder: A Preliminary Report on the Clinical Importance of Objective and Subjective Reduction of Total Sleep Time

To confirm and extend previous findings on the relationships between executive functioning (EF) and insomnia, as well as the available evidence on the associations between personality traits and insomnia, 30 consecutively-admitted insomnia participants and 30 community dwelling adult participants matched on age, gender and educational level, were administered a battery of EF measures and the Personality Inventory for DSM-5 (PID-5). Insomnia participants underwent two full-night polysomnographic (PSG) recording, followed by a morning assessment of subjective sleep parameters. A misperception index (MI) was computed in order to identify participants characterized by objective insomnia and non-objective insomnia. The EF performance associations between insomnia and poor performance on selected executive functions was confirmed. However, the objective insomnia and non-objective insomnia sub-groups show significant differences on specific EF indices, as well as on dysfunctional personality dimensions

Observational study of sleep-related disorders in Italian patients with Parkinson's disease: usefulness of the Italian version of Parkinson's disease sleep scale.

Sleep disturbances are common in patients with Parkinson's disease (PD). We aimed to evaluate prevalence and severity of nighttime sleep disturbances in Italian PD patients and to validate the Italian version of the Parkinson's disease sleep scale. A total of 221 PD patients and 57 healthy controls participated in a cross-sectional study with retest. PDSS, Epworth Sleepiness Scale (ESS), Hamilton Depression Rating Scale, Unified Parkinson's Disease Rating Scale (UPDRS), and Hoehn and Yahr staging were applied. PDSS total and individual items scores from patients were significantly lower than those in controls. Internal consistency of PDSS scale was satisfactory and intraclass correlation coefficient for test-retest reliability was 0.96 for total PDSS score. A significant negative correlation was found between total PDSS and ESS scores, and between total PDSS and HDRS scores. PDSS scores were also related to UPDRS sections II, III and IV, and H&Y stage. PDSS and ESS scores were not related to levodopa equivalent dose. Daytime sleepiness, depressive symptoms and disease severity correlate with sleep disturbances in Italian PD patients. The PDSS is a valid and reliable tool to evaluate sleep disturbances in Italian patients. © 2011 Springer-Verlag

Cognitive Reserve in Isolated Rapid Eye-Movement Sleep Behavior Disorder

Isolated rapid-eye-movement sleep behaviour disorder (RBD) is considered the prodromal stage of α-synucleinopathies (e.g., Parkinson’s disease and dementia with Lewy bodies); however, iRBD patients show a wide variety in the progression timing (5–15 years). The model of cognitive reserve (CR) might contribute to explaining this phenomenon. Our exploratory study aimed to evaluate, for the first time, the impact of CR level on cognitive performance in polysomnography-confirmed iRBD patients. Fifty-five iRBD patients (mean age ± SD: 66.38 ± 7.51; M/F 44/11) underwent clinical and neuropsychological evaluations at the time of diagnosis. The CR Index questionnaire was part of the clinical assessment. We found that iRBD patients with high levels of CR showed: (i) the lowest percentage of mild cognitive impairment (10%), and (ii) the best performance in visuo-constructive and verbal memory functions (i.e., the recall of the Rey–Osterrieth complex figure test). Our results suggest that CR might help iRBD patients better cope with the cognitive decline related to the neurodegenerative process, providing the first preliminary findings supporting CR as a possible protective factor in this condition. This might pave the way for future longitudinal studies to evaluate the role of CR as a modulating factor in the timing of iRBD conversion and cognitive deterioration development.</p