Functional connectivity and topology in patients with restless legs syndrome: a case-control resting-state functional magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Functional connectivity studies revealed alterations within thalamic, salience, and default mode networks in restless legs syndrome patients. METHODS: Eighty-two patients with restless legs syndrome (untreated, n = 30; on dopaminergic medication, n = 42; on alpha-2-delta ligands as mono- or polytherapy combined with dopaminergic medication, n = 10), and 82 individually age- and gender-matched healthy controls were studied with resting-state functional magnetic resonance imaging. Connectivity of 12 resting-state networks was investigated with independent component analysis, and network topology was studied with graph methods among 410 brain regions. RESULTS: Patients with restless legs syndrome showed significantly higher connectivity within salience (p = 0.029), executive (p = 0.001), and cerebellar (p = 0.041) networks, as well as significantly lower (p < 0.05) cerebello-frontal communication compared to controls. In addition, they had a significantly higher (p < 0.05) clustering coefficient and local efficiency in motor and frontal regions; lower clustering coefficient in the central sulcus; and lower local efficiency in the central opercular cortex, temporal, parieto-occipital, cuneus, and occipital regions compared to controls. Untreated patients had significantly lower (p < 0.05) cerebello-parietal communication compared to healthy controls. Connectivity between the thalamus and frontal regions was significantly increased (p < 0.05) in patients on dopaminergic medication compared to untreated patients and controls. CONCLUSIONS: Networks with higher intranetwork connectivity (i.e., salience, executive, cerebellar) and lower cerebello-frontal connectivity in the restless legs syndrome patients, as well as lower cerebello-parietal connectivity in untreated patients, correspond to regions associated with attention, response inhibitory control, and processing of sensory information. Intact cerebello-parietal communication and increased thalamic connectivity to the prefrontal regions in patients on dopaminergic medication suggests a treatment effect on thalamus.

Standard procedures for the diagnostic pathway of sleep-related epilepsies and comorbid sleep disorders: an EAN, ESRS and ILAE-Europe consensus review.

BACKGROUND AND PURPOSE: Some epilepsy syndromes (sleep-related epilepsies, SREs) have a strong link with sleep. Comorbid sleep disorders are common in patients with SRE and can exert a negative impact on seizure control and quality of life. Our purpose was to define the standard procedures for the diagnostic pathway of patients with possible SRE (scenario 1) and the general management of patients with SRE and comorbidity with sleep disorders (scenario 2). METHODS: The project was conducted under the auspices of the European Academy of Neurology, the European Sleep Research Society and the International League Against Epilepsy Europe. The framework entailed the following phases: conception of the clinical scenarios; literature review; statements regarding the standard procedures. For the literature search a stepwise approach starting from systematic reviews to primary studies was applied. Published studies were identified from the National Library of Medicine's MEDLINE database and Cochrane Library. RESULTS: Scenario 1: Despite a low quality of evidence, recommendations on anamnestic evaluation and tools for capturing the event at home or in the laboratory are provided for specific SREs. Scenario 2: Early diagnosis and treatment of sleep disorders (especially respiratory disorders) in patients with SRE are likely to be beneficial for seizure control. CONCLUSIONS: Definitive procedures for evaluating patients with SRE are lacking. Advice is provided that could be of help for standardizing and improving the diagnostic approach of specific SREs. The importance of identifying and treating specific sleep disorders for the management and outcome of patients with SRE is underlined.

Objective rest-activity cycle analysis by actigraphy identifies isolated rapid eye movement sleep behavior disorder.

BACKGROUND AND PURPOSE: Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is characterized by abnormal behaviours during REM sleep. Several studies showed that iRBD is a prodromal stage of synucleinopathies. Therefore, identifying iRBD in the general population is of utmost importance. In this study, we explore whether the assessment of rest-activity rhythm features can distinguish patients with iRBD from patients with disorders characterized by other pathological motor activity during sleep and healthy controls. METHODS: Nineteen patients with video-polysomnographic diagnosis of iRBD, 39 patients with other disorders with motor activity during sleep [19 with restless leg syndrome (RLS) and 20 with untreated sleep apnea syndrome (SAS)] and 16 healthy controls underwent 2-week actigraphy and video-polysomnography, and completed REM sleep behavior disorder screening questionnaires. Non-parametric analyses were applied to assess the rest-activity rhythm features. RESULTS: Patients with iRBD showed lower sleep efficiency, increased estimated wake after sleep onset and increased frequency of prolonged activity bouts compared to those with RLS and controls, while no difference emerged compared with SAS patients. Moreover, patients with iRBD presented increased occurrence of estimated nap in comparison to those with RLS, those with SAS and controls. The I < O, a 24-h measure that expresses the relationship between nocturnal and diurnal motor activity intensity, distinguished patients with iRBD from those with RLS, those with SAS and controls, with an area under the curve greater than that of REM sleep behavior disorder screening questionnaires. An I < O of 98.32 shows the best balance between sensitivity (63.2%) and specificity (89.1%). DISCUSSION: The I < O index distinguished iRBD patients from those with other pathological motor activity during sleep and controls, confirming its use as an objective measure suitable to screen large at-risk populations.

Basic clinical features do not predict dopamine transporter binding in idiopathic REM behavior disorder.

REM sleep behavior disorder (RBD) is strongly associated with development of Parkinson's Disease and other α-synuclein-related disorders. Dopamine transporter (DAT) binding deficit predicts conversion to α-synuclein-related disorders in individuals with RBD. In turn, identifying which individuals with RBD have the highest likelihood of having abnormal DAT binding would be useful. The objective of this analysis was to examine if there are basic clinical predictors of DAT deficit in RBD. Participants referred for inclusion in the RBD cohort of the Parkinson Progression Markers Initiative were included. Assessments at the screening visit including DAT SPECT imaging, physical examination, cognitive function screen, and questionnaire-based non-motor assessment. The group with DAT binding deficit (n = 49) was compared to those without (n = 26). There were no significant differences in demographic or clinical features between the two groups. When recruiting RBD cohorts enriched for high risk of neurodegenerative disorders, our data support the need for objective biomarker assessments.

Sleep and sleep disorders in Franz Kafka's narrative works.

OBJECTIVE: As Franz Kafka, one of the most important writers of the 20th century, suffered from severe chronic insomnia disorder and inadequate sleep hygiene that impaired his quality of life, we speculated that sleep disorders would be found in his narrative works. METHODS: We read Kafka's complete literary works looking for references to sleep and sleep disorders, excluding insomnia. RESULTS: In Kafka's works, sleeping well and for a long time was used as an allegory of having a pleasant life. We found that some of his characters were disturbed by excessive daytime sleepiness and sleep attacks, circadian rhythm sleep-wake disorders, sleep-related hallucinations, sleep symptoms in the context of heart failure and abnormal sleep behaviors (eg, sleep-talking, sleep-crying, sleep-laughing and dream-enacting motor manifestations). Kafka also recalled a dream where bruxism occurred. CONCLUSION: Kafka's narrative works contain characters suffering from a wide variety of sleep disorders which in some cases represent autobiographical elements but not in others indicating that he was an astute observer of people, sleep and its disorders. The inclusion of characters suffering from sleep disorders was used by Kafka as a literary resource to enrich his texts.

The insomnia of Franz Kafka.

OBJECTIVE: To characterize the insomnia suffered by Franz Kafka (1883-1924), one of the most important literary figures of the 20th century. METHODS: We read Kafka's diaries and private correspondence to his fiancée, friends, editors and relatives looking for references to his insomnia. RESULTS: We found 292 references to insomnia indicating that Kafka suffered from chronic insomnia disorder that originated from and was maintained by the following predisposing and precipitating factors: (1) a complex personality predisposing to an increased arousal level, (2) intrusive thoughts and ruminations at bedtime, (3) excessive worrying about sleep loss and its daytime consequences, and (4) an extraordinary intolerance to noise. Since he could not sleep at night and felt the necessity to compose his literary works in an absolutely quiet environment, Kafka deliberately changed his sleep-wake schedule so he could write at night and nap in the afternoon. These maladaptive sleep habits perpetuated his insomnia and led to chronic sleep deprivation resulting in fatigue, lack of concentration and sleep-related auditory, tactile and visual hallucinations. Kafka sought help in alternative medicine however this was ineffective in improving his insomnia. CONCLUSIONS: Kafka suffered from chronic insomnia disorder and had inadequate sleep hygiene resulting in chronic sleep deprivation. These sleep problems impaired Kafka's quality of life.

[Frequent neurological diseases associated with the restless legs syndrome]. / Häufige neurologische Erkrankungen assoziiert mit dem Restless-legs-Syndrom.

BACKGROUND: Restless legs syndrome (RLS) is a common neurological disease. Studies have shown that RLS is associated with a variety of medical and neurological disorders. OBJECTIVES: Using the example of three associated neurological diseases, the significance for everyday therapy decisions is assessed. MATERIAL AND METHODS: A systematic search was carried out in PubMed for all studies with the keyword "RLS" in combination with polyneuropathies (PNP), Parkinson's disease (PD) and multiple sclerosis (MS) and classified according to the methodology in high, medium or low study quality. RESULTS: Of 16 studies on RLS and MS, 10 were rated as "high". The high association frequency of RLS in MS between 13.3% and 65.1% (the variability possibly originates from different methods) prevents further statements about the prevalence. Within 30 studies on Parkinson's disease 17 were classified as having a high quality. In patients with Parkinson disease RLS occurs most frequently during therapy and is related to the duration of dopaminergic treatment. In patients with polyneuropathy, only 5 out of 24 studies were classified as being of high quality and an increased RLS prevalence was detected for acquired polyneuropathies with heterogeneous data for hereditary forms. CONCLUSION: There is an increased prevalence of association with RLS for the diseases discussed. This prevalence is possibly determined by the pathophysiology of these disorders. These diseases are possibly characterized by genetic predispositions as well, which can hopefully be classified more accurately in the future.