Structural and functional multilayer network analysis in restless legs syndrome patients.

The combination of brain structural and functional connectivity offers complementary insights into its organisation. Multilayer network analysis explores various relationships across different layers within a single system. We aimed to investigate changes in the structural and functional multilayer network in 69 patients with primary restless legs syndrome (RLS) compared with 50 healthy controls. Participants underwent diffusion tensor imaging (DTI) and resting state-functional magnetic resonance imaging (rs-fMRI) using a three-tesla MRI scanner. We constructed a structural connectivity matrix derived from DTI using a DSI program and made a functional connectivity matrix based on rs-fMRI using an SPM program and CONN toolbox. A multilayer network analysis, using BRAPH program, was then conducted to assess the connectivity patterns in both groups. At the global level, significant differences there were between the patients with RLS and healthy controls. The average multiplex participation was lower in patients with RLS than in healthy controls (0.804 vs. 0.821, p = 0.042). Additionally, several regions showed significant differences in the nodal level in multiplex participation between patients with RLS and healthy controls, particularly the frontal and temporal lobes. The regions affected included the inferior frontal gyrus, medial orbital gyrus, precentral gyrus, rectus gyrus, insula, superior and inferior temporal gyrus, medial and lateral occipitotemporal gyrus, and temporal pole. These results represent evidence of diversity in interactions between structural and functional connectivity in patients with RLS, providing a more comprehensive understanding of the brain network in RLS. This may contribute to a precise diagnosis of RLS, and aid the development of a biomarker to track treatment effectiveness.

An FP's guide to caring for patients with seizure and epilepsy.

Optimizing your care requires that you distinguish between provoked and unprovoked seizures and focus on key elements of the patient's history.

Continuous EEG Characteristics in Critically ill Patients Presenting With Seizures Prior to Death From Cardiac Arrest.

Background: There have been limited reports about brain activity during cardiac arrest. Here we report 4 patients presenting with seizure who had cardiac arrest leading to their deaths while being on continuous video-EEG (cVEEG) monitoring and one-lead cardiac telemetry. Purpose: We illustrate characteristic stepwise EEG and EKG changes in these critically ill patients prior to their death. Research Design/Study Sample: All patients showed progressive broad spectrum of cardiac arrhythmias at or before the beginning of EEG suppression while there were no such changes seen in a control group of 4 randomly selected patients without cardiac arrest who had seizure on presentation and underwent cVEEG monitoring. Data Collection and Results: There was a progressive decline in EEG potentials associated with decreasing heart rate starting from the posterior region, more pronounced on the left, progressing to complete unilateral deactivation of the left fronto-central head regions while the right-sided networks became hyperactive before bilateral deactivation by the time of asystole. Conclusions: This case series provides a rare opportunity to compare EEG and EKG changes in patients who died while being on continuous EEG and EKG monitoring from hours to minutes prior to cardiac arrest and death.

Glymphatic system dysfunction in restless legs syndrome: evidenced by diffusion tensor imaging along the perivascular space.

STUDY OBJECTIVES: There is growing evidence pointing at glymphatic system dysfunction in diseases with circadian disruption, such as sleep disorders. Lower diffusivity in the direction of perivascular space has been shown in several neurological and sleep-related disorders; however, its role in restless legs syndrome (RLS) is unclear. We hypothesized that similarly, in RLS the diffusivity in glymphatic system is decreased. Here, we aimed to evaluate glymphatic system functionality in patients with RLS, compare it to healthy controls, and analyze the correlation between its function and clinical characteristics. METHODS: Sixty-nine patients with primary RLS and 51 healthy controls were recruited at a tertiary hospital. All participants underwent diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI) using a 3T MRI scanner, and the DTI along the perivascular space (DTI-ALPS) index was calculated using DTI data. We compared the DTI-ALPS index between the patients with RLS and healthy controls. We also conducted the correlation analysis between the DTI-ALPS index and clinical characteristics, including age, age of onset, symptom duration, and RLS severity. RESULTS: DTI-ALPS index differed significantly between the patients with RLS and healthy controls; the DTI-ALPS index in the patients with RLS was lower than that in the healthy controls (1.48 vs. 0.60, p = 0.008). There was no significant correlation between the DTI-ALPS index and clinical characteristics. CONCLUSION: A significantly lower DTI-ALPS index in patients with RLS suggests that the glymphatic system function is impaired in patients with RLS.

Transcranial Alternating Current Stimulation (tACS) as a Treatment for Insomnia.

We investigated the effects of transcranial alternating stimulation (tACS) in patients with insomnia. Nine patients with chronic insomnia underwent two in-laboratory polysomnography, 2 weeks apart, and were randomized to receive tACS either during the first or second study. The stimulation was applied simultaneously and bilaterally at F3/M1 and F4/M2 electrodes (0.75 mA, 0.75 Hz, 5-minute). Sleep onset latency and wake after sleep onset dropped on the stimulation night but they did not reach statistical significance; however, there were significant improvements in spontaneous and total arousals, sleep quality, quality of life, recall memory, sleep duration, sleep efficiency, and daytime sleepiness.

Cognitive behavioral therapy for insomnia in restless legs syndrome patients.

OBJECTIVES: The purpose of this study was to investigate the effects of cognitive behavioral therapy for insomnia (CBTI) in patients with Restless Legs Syndrome (RLS). METHODS: This is a randomized controlled study. The patients were sequentially selected and randomly assigned to either a CBTI group or a non-CBTI group. A total of 25 RLS patients with comorbid insomnia were recruited from a tertiary university hospital sleep center. Twelve were assigned to the CBTI group, and 13 were assigned to the non-CBTI group. The CBTI group received 4 sessions of behavioral therapy, while the non-CBTI group received one informative session on sleep hygiene. All patients completed sleep and psychiatric-related questionnaires. In addition, each individual completed a one-week sleep log for collecting subjective sleep data and actigraphy for objective sleep data. RESULTS: After conducting the CBTI, there were significant improvements in severity of insomnia symptoms, subjective sleep efficiency, total sleep time, latency to sleep onset, wake after sleep onset, objective latency to sleep onset, and anxiety in the CBTI group as compared to the non-CBTI group. The effect of CBTI on sleep-related data was maintained for up to three months. CONCLUSIONS: CBTI was effective in RLS patients by improving sleep quality and anxiety symptoms. CBTI may be considered in clinical practice for RLS patients with comorbid insomnia.

Clinical characteristics of Korean pediatric patients with restless legs syndrome.

OBJECTIVES: Restless legs syndrome (RLS) is a common neurological disorder but it is not sufficiently recognized in children and adolescents. It often overlaps with growing pains in children, and as a result the clinical characteristics of pediatric RLS are not well studied, especially in Asia. The purpose of this study is to investigate the clinical characteristics of pediatric RLS patients in Korea and compare it to those of adult RLS patients. METHODS: We retrospectively reviewed the medical records of all pediatric RLS patients (≤18 years) from January 2015 to December 2018 in a regional tertiary hospital sleep center. We randomly selected adult primary RLS patients without comorbid medical disorders from our sleep center's dataset as controls. The number of controls was determined to be twice the number of pediatric RLS patients according to sample size calculation. The clinical and polysomnographic (PSG) characteristics of both groups were compared. The independent t-test, chi-squared test, and Fisher's exact test were used for analyzing quantitative data between the two groups and p < 0.05 was considered statistically significant. RESULTS: Twenty-nine primary pediatric RLS patients and 57 adult RLS patients were enrolled. Pediatric RLS patients showed equal prevalence between sexes, as opposed to adults where there is female predominance. Ferritin level was significantly lower in pediatric patients, although it remained within the normal range. Also, pediatric RLS patients showed less severe RLS symptoms and had better sleep quality than adults did in both objective and subjective measures. In addition, PLMS was shown to be less common in pediatric RLS patients compared to adults. CONCLUSIONS: Pediatric RLS patients showed relatively mild to moderate RLS symptoms and a smaller likelihood of experiencing PLMS than adult patients, which is comparable to similar western studies. Long-term evaluation of a patient's clinical course through multicenter clinical studies is strongly suggested for the future.

Symptom-related changes in current perception threshold of restless legs syndrome.

Few studies have investigated the mechanisms responsible for the symptoms of restless legs syndrome (RLS). However, these studies were mainly performed during the asymptomatic period and therefore their findings might not apply to changes in sensory processing that occur during the symptomatic period. The objective of this study was to investigate the function of sensory nerve fibres in RLS patients using the current perception threshold (CPT) test during the daytime and in the presence of symptoms. Ninety-three patients with RLS and 34 healthy controls were included in the study. RLS patients were further divided into two subgroups, those who were experiencing RLS symptoms during the CPT test (symptom+) and those without symptoms (symptom-). Demographic data, RLS rating scale score and visual analogue scale were collected. Of the 127 enrolled subjects, CPT values were significantly lower in RLS patients than in controls for all three frequencies. Among the control and RLS subgroups (53 symptom+, 40 symptom-), symptom+ patients showed lower CPT values than controls. This finding indicates a relative hyperaesthetic state in the sensory afferents of peripheral nerves in symptom+ patients. There were no significant differences between the symptom- group and controls. The significantly lower CPT values for all three frequencies in symptom+ patients suggest that central sensory processing disturbance of sensory nerve fibres' input may be involved in the development of symptoms in RLS patients.

The clinical utility of non-invasive video-electroencephalographic monitoring has been diversifying.

BACKGROUND: Inpatient long-term video-electroencephalographic (VEEG) monitoring has been used extensively for differential diagnosis of paroxysmal events. We evaluated the diagnostic yield and clinical utility of VEEG performed in a comprehensive epilepsy center. METHOD: We retrospectively reviewed all cases of VEEG performed from May 2003 to April 2018. We analyzed the data to determine its clinical utility and diagnostic yield. RESULTS: A total of 1335 cases were reviewed. After excluding 147 cases of intracranial recording and 163 cases with incomplete medical records, 1025 cases of VEEG were included. The mean duration of VEEG was 2.3 ± 1.6 days (range = 1-14). A total of 763 VEEGs documented epileptic seizures or interictal epileptiform discharges (IEDs) to confirm the diagnosis of epilepsy. There were 99 psychogenic non-epileptic seizure, 36 status epilepticus, and 34 VEEGs which revealed generalized or focal slow activities without any clinical seizures or IEDs. VEEG was normal in 170 cases. The diagnostic yield of VEEG varied from 83.4 to 88.4% depending on its definition. The proportion of epilepsy in total cases of VEEG continued to decrease from 77.2 to 61.4%. In contrast, the proportion of normal VEEG steadily increased from 4.1 to 24.1% during the same time period. CONCLUSIONS: This study ascertained how useful VEEG is and the utility of VEEG has been diversifying in clinical circumstances beyond epilepsy. VEEG can play a pivotal role in the diagnostic approach to epilepsy and its differential diagnoses.

Default mode network deactivation in pediatric temporal lobe epilepsy: Relationship to a working memory task and executive function tests.

OBJECTIVES: Children with temporal lobe epilepsy (TLE) exhibit executive dysfunction on traditional neuropsychological tests. There is limited evidence of different functional network alterations associated with this clinical executive dysfunction. This study investigates working memory deficits in children with TLE by assessing deactivation of the default mode network (DMN) on functional Magnetic Resonance Imaging (fMRI) and the relationship of DMN deactivation with fMRI behavioral findings and neuropsychological test performance. EXPERIMENTAL DESIGN: fMRI was conducted on 15 children with TLE and 15 healthy controls (age: 8-16 years) while performing the N-back task in order to assess deactivation of the DMN. N-back accuracy, N-back reaction time, and neuropsychological tests of executive function (Delis-Kaplan Executive Function System [D-KEFS] Color-Word Interference and Card Sort tests) were also assessed. PRINCIPAL OBSERVATIONS: During the N-back task, children with TLE exhibited significantly less deactivation of the DMN, primarily in the precuneus/posterior cingulate cortex compared with controls. These alterations significantly correlated with N-back behavioral findings and D-KEFS results. CONCLUSIONS: Children with TLE exhibit executive dysfunction which correlates with DMN alterations. These findings suggest that the level of deactivation of specific functional networks may contribute to cognitive impairment in children with TLE. The findings also indicate that children with TLE have network alterations in extratemporal lobe brain regions.

The first night effect during polysomnography, and patients' estimates of sleep quality.

We surveyed patients the next morning after in-laboratory polysomnography (PSG) to compare the first night effect (FNE) and reverse first night effect (RFNE) in different sleep disorders. A questionnaire was given to 852 patients with insomnia (n = 171), restless legs syndrome (n = 186), obstructive sleep apnea (n = 369), simple snoring (n = 54), REM sleep behavior disorder (n = 39), and hypersomnia (n = 33). FNE was seen in 48.9%, 30.5% slept as usual, and 20.6% had RFNE. The highest incidences of FNE were seen in OSA, simple snoring, hypersomnia, and in men. We propose to use these findings as a reference when interpreting nocturnal in-laboratory PSG results.

Case of fatal familial insomnia caused by a d178n mutation with phenotypic similarity to Hashimoto's encephalopathy.

Fatal familial insomnia (FFI) is a rare prion disease commonly inherited in an autosomal dominant pattern from a mutation in the PRioN Protein (PRNP) gene. Hashimoto's encephalopathy (HE) is characterised by encephalopathy associated with antithyroid peroxidase (TPO) or antithyroglobulin (Tg) antibodies. These two conditions characteristically have differing clinical presentations with dramatically different clinical course and outcomes. Here, we present a case of FFI mimicking HE. A woman in her 50s presented with worsening confusion, hallucinations, tremor and leg jerks. Several maternal relatives had been diagnosed with FFI, but the patient had had negative genetic testing for PRNP. MRI of brain, cervical and thoracic spine were unremarkable except for evidence of prior cervical transverse myelitis. Cerebrospinal fluid analysis was normal. Anti-TPO and anti-Tg antibodies were elevated. She was started on steroids for possible HE and showed improvement in symptoms. Following discharge, the results of her PRNP gene test returned positive for variant p.Asp178Asn.

Diagnosis and Surgical Treatment of Drug-Resistant Epilepsy.

Despite appropriate trials of at least two antiepileptic drugs, about a third of patients with epilepsy remain drug resistant (intractable; refractory). Epilepsy surgery offers a potential cure or significant improvement to those with focal onset drug-resistant seizures. Unfortunately, epilepsy surgery is still underutilized which might be in part because of the complexity of presurgical evaluation. This process includes classifying the seizure type, lateralizing and localizing the seizure onset focus (epileptogenic zone), confirming the safety of the prospective brain surgery in terms of potential neurocognitive deficits (language and memory functions), before devising a surgical plan. Each one of the above steps requires special tests. In this paper, we have reviewed the process of presurgical evaluation in patients with drug-resistant focal onset epilepsy.

Comorbid Insomnia With Obstructive Sleep Apnea: Clinical Characteristics and Risk Factors.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and chronic insomnia are two common sleep disorders and both are considered independent risk factors for heart disease. The aim of this study was to investigate the prevalence of comorbid insomnia with OSA and to compare its clinical characteristics with those of OSA without insomnia. METHODS: Patients who visited two tertiary university hospital sleep centers were screened. Those with a diagnosis of OSA using polysomnography were divided into two groups based on their scores on the Korean version of the Insomnia Severity Index (ISI-K): OSA with insomnia (OSA+I) (ISI-K score ≥ 15) and OSA without insomnia (OSA-I) (ISI-K score < 15). Subjective symptoms were evaluated using sleep questionnaires including ISI-K. Demographic and clinical characteristics of OSA+I and OSA-I were compared. RESULTS: Out of 476 patients with OSA, 139 (29.2%) had significant insomnia. Patients in the OSA+I group had a higher percentage of females (35.3% versus 19.6%, P < .001) and have higher rates of heart disease (19.4% versus 8.6%, P < .001). OSA+I group showed lower quality of life, lower quality of sleep, higher sleep propensity, and higher depression as measured by the Korean versions of the Short-Form 36-Item Health Survey, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Beck Depression Inventory, respectively. There were no significant differences in adherence to continuous positive airway pressure between the groups. CONCLUSIONS: There is a high prevalence of comorbid insomnia with OSA (29.2%), consistent with previous findings in Western studies. Comorbid insomnia with OSA may constitute a cumulative risk factor for cardiovascular disease. These findings warrant further investigation into the mechanisms involved in its pathogenesis and devising more efficient treatments.

Quantitative sensory test for primary restless legs syndrome/Willis-Ekbom disease using the current perception threshold test.

BACKGROUND: Restless legs syndrome/Willis-Ekbom disease (RLS/WED) is a sensorimotor neurological disorder, and it is especially aggravated at night. The purpose of this study was to investigate the diurnal sensory dysfunction in primary RLS/WED using the current perception threshold (CPT) test, compared to healthy controls. METHODS: Thirty primary RLS/WED subjects and 30 healthy controls were enrolled. The severity of RLS/WED and sleep problems were evaluated in all subjects. Peripheral polyneuropathy was excluded through neurological examination and nerve conduction study. We used the Neurometer® system for the CPT test and applied three different parameters (2000 Hz, 250 Hz, and 5 Hz), to stimulate both big toes. The CPT test was performed twice, once during the asymptomatic daytime period and again in the evening, when the patients were symptomatic. RESULTS: The mean ages of the RLS/WED group and controls were 50.5 ± 11.7 (22; 73.3% female), and 46.3 ± 11.4 (24; 80.0% female), respectively. The mean international RLS/WED study group severity scale score was 28.6 ± 4.25. There was no significant difference in the current perception thresholds between the RLS/WED patients and controls in daytime. However, the RLS/WED patients had lower mean CPT measurements for all three stimulation protocols in the evening (2000 Hz: 393.2 ± 93.7 vs 430.8 ± 79.6, 250 Hz: 172.0 ± 48.4 vs 198.5 ± 38.2, and 5 Hz: 98.0 ± 34.1 vs 124.6 ± 31.3), while the healthy controls showed no difference. CONCLUSIONS: RLS patients showed a lower CPT in the evening. The diurnal variation of hyperalgesia in RLS/WED patients indicates a central (circadian) sensory processing disturbance rather than a peripheral disturbance.

Quality of life in patients with an idiopathic rapid eye movement sleep behaviour disorder in Korea.

There have been few quality of life studies in patients with idiopathic rapid eye movement sleep behaviour disorder. We compared the quality of life in idiopathic rapid eye movement sleep behaviour disorder patients to healthy controls, patients with hypertension, type 2 diabetes mellitus without complication and idiopathic restless legs syndrome. Sixty patients with idiopathic rapid eye movement sleep behaviour disorder (24 female; mean age: 61.43 ± 8.99) were enrolled retrospectively. The diagnosis was established based on sleep history, overnight polysomnography, neurological examination and Mini-Mental State Examination to exclude secondary rapid eye movement sleep behavior disorder. All subjects completed questionnaires, including the Short Form 36-item Health Survey for quality of life. The total quality of life score in idiopathic rapid eye movement sleep behaviour disorder (70.63 ± 20.83) was lower than in the healthy control group (83.38 ± 7.96) but higher than in the hypertension (60.55 ± 24.82), diabetes mellitus (62.42 ± 19.37) and restless legs syndrome (61.77 ± 19.25) groups. The total score of idiopathic rapid eye movement sleep behaviour disorder patients had a negative correlation with the Pittsburg Sleep Quality Index (r = -0.498, P < 0.001), Insomnia Severity Index (r = -0.645, P < 0.001) and the Beck Depression Inventory-2 (r = -0.694, P < 0.001). Multiple regression showed a negative correlation between the Short Form 36-item Health Survey score and the Insomnia Severity Index (ß = -1.100, P = 0.001) and Beck Depression Inventory-2 (ß = -1.038, P < 0.001). idiopathic rapid eye movement sleep behaviour disorder had a significant negative impact on quality of life, although this effect was less than that of other chronic disorders. This negative effect might be related to a depressive mood associated with the disease.