Association of low serum ferritin levels with augmentation in patients with restless legs syndrome: A systematic review and meta-analysis.

BACKGROUND: Augmentation of restless legs syndrome (RLS) is an iatrogenic side effect induced by dopaminergic agents, and it is a major cause of therapeutic failure. Iron deficiency is a risk factor for RLS, but its effects on the development of RLS augmentation are unclear. This meta-analysis aimed to elucidate the association between serum ferritin and RLS augmentation. METHODS: We searched the PubMed, Cochrane Library, Embase, ClinicalKey, ScienceDirect, and ProQuest databases for studies comparing the serum ferritin levels of patients with augmented RLS and nonaugmented RLS. A meta-analysis based on a random-effects model was conducted. Levodopa equivalent dose (LED), International Restless Legs Study Group Severity Rating Scale (IRLS), and serum hemoglobin levels were also analyzed. RESULTS: Six observational studies fulfilled the eligibility criteria of this meta-analysis. A total of 220 RLS patients with augmentation and 687 RLS patients without augmentation were included. The results revealed that augmented RLS was significantly associated with low serum ferritin levels (p = 0.002), high LEDs (p = 0.026), and nonsignificantly associated with high IRLS scores (p = 0.227). CONCLUSIONS: A low serum ferritin level is associated with RLS augmentation. For patients with RLS who are iron deficient, iron supplements can not only relieve their fundamental RLS symptoms but also lower the risk of RLS augmentation. Moreover, non-dopminergic agents should be considered as the first-line treatment for patients with persistent low serum ferritin levels or those with moderate to severe RLS to prevent augmentation.

Association between subclinical epileptiform discharge and the behavioral and psychological symptoms in patients with Alzheimer's dementia.

OBJECTIVES: Behavioral and psychological symptoms of dementia (BPSD) are highly prevalent in patients with Alzheimer's disease (AD), causing burdens on caregivers. Behavioral and psychological symptoms of dementia and subclinical epileptiform discharge (SED) increased with the disease course of AD. However, the interaction between them was still unknown. The present study aimed to evaluate the associations between SED and BPSD. METHODS/DESIGN: Patients with AD from Kaohsiung Municipal Ta-tung Hospital were included in this study. International 10-20 system scalp electroencephalography (EEG) for 13 min was performed to detect SED. Behavioral and psychological symptoms of dementia was assessed by neuropsychiatric inventory (NPI) questionnaires. The occurrence of BPSD subsyndromes was compared between patients with and without SED. RESULTS: Two hundred sixty-three adult patients qualified for the inclusion criteria and were enrolled in this study. The mean age of patients was 80.2 years, and approximately 62% were women. 17.1% of patients showed SED on EEG. Apathy was the most commonly reported BPSD subsyndrome in this cohort. There was no significant difference in the prevalence of BPSD between patients with and without SED. (75.6% vs. 67.4%, p = 0.2806). However, the NPI score of irritability subsyndrome was significantly higher in the SED (+) group (2.6 ± 3.7 vs. 1.2 ± 2.7, p = 0.0028). In addition, subclinical epileptiform discharge in the frontal lobe was associated with a considerably higher occurrence of hyperactivity subsyndrome, including irritability. CONCLUSIONS: SED may not be a direct cause of BPSD, but the presence of SED may affect the manifestation of BPSD.

Reduction in the propensity of rapid eye movement sleep and phasic-to-tonic ratio in patients with refractory epilepsy.

STUDY OBJECTIVES: Patients with epilepsy exhibit disturbed sleep architecture and shorter rapid eye movement (REM) sleep compared with healthy controls. REM sleep consists of two microstates, phasic and tonic REM. Studies suggest that epileptic activity is suppressed in phasic but not in tonic REM. However, changes in the REM microstructure in patients with epilepsy are still unknown. Therefore, this study evaluated the differences in REM microstructure between patients with refractory and medically controlled epilepsy. METHODS: This retrospective case-control study included patients with refractory and medically controlled epilepsy. Sleep parameters of the patients were recorded by standard polysomnography. In addition, the microstructures of sleep and REM sleep were compared between the two epilepsy groups. RESULTS: Forty-two patients with refractory epilepsy and 106 with medically controlled epilepsy were evaluated. The refractory group showed significantly decreased REM sleep (p = 0.0062), particularly in the first and second sleep cycles (p = 0.0028 and 0.00482, respectively), as well as longer REM latency (p = 0.0056). Eighteen and 28 subjects in the refractory and medically controlled epilepsy groups, respectively, with comparable REM sleep percentages, underwent REM microstructure examination. Phasic REM sleep was significantly lower in the refractory group (4.5% ± 2.1% vs. 8.0% ± 4.1%; p = 0.002). In addition, the phasic-to-tonic ratio was significantly decreased (4.8 ± 2.3 vs. 8.9 ± 4.9; p = 0.002) and negatively associated with refractory epilepsy (coefficient = -0.308, p = 0.0079). CONCLUSION: Patients with refractory epilepsy exhibited REM sleep disturbance at both macro and microstructure levels.

Restless Legs Syndrome in Patients with Epilepsy: Risk analysis, Polysomnography, and Quality of Life evaluation.

STUDY OBJECTIVES: Restless legs syndrome (RLS) is a circadian rhythm related sensorimotor disorder due to brain iron deficiency, with lesion sites at the putamen and substantia nigra. However, epilepsy is a disease with abnormal electric discharge from the cortex and can be triggered with iron disequilibrium. We designed a case-control study to discover the association between epilepsy and RLS. METHODS: A total of 24 patients with epilepsy and RLS and 72 patients with epilepsy without RLS were included. Most of the patients underwent polysomnography and video electroencephalogram tests and took sleep questionnaires. We collected information on seizure characteristics, including general or focal onset, epileptogenic focus, current antiseizure medications, medically responsive epilepsy or refractory epilepsy, and nocturnal attacks. The sleep architectures of the two groups were compared. We analyzed the risk factors for RLS using multivariate logistic regression. RESULTS: Among the patients with epilepsy, the occurrence of RLS was associated with refractory epilepsy (OR 6.422, P = 0.002) and nocturnal seizures (OR 4.960, P = 0.005). Sleep parameters were not significantly associated with RLS status. Quality of life was significantly impaired in the group with RLS in both the physical and mental domains. CONCLUSIONS: Refractory epilepsy and nocturnal seizures were strongly correlated with RLS in patients with epilepsy. RLS should be considered a predictable comorbidity in patients with epilepsy. The management of RLS not only led to better control of the patient's epilepsy but also improved their quality of life.

Association between Subclinical Epileptiform Discharge and the Severity of Cognitive Decline in Alzheimer's Disease: A Longitudinal Cohort Study.

BACKGROUND: Alzheimer's disease (AD) is the most common type of dementia. Aging is a risk factor for both AD and seizures. Subclinical epileptiform discharge (SED) has no evident clinical manifestation in patients with AD. Therefore, SED is liable to be overlooked in these patients since electroencephalography is not routinely performed in clinical settings. Previous studies about the association between SED and AD have yielded inconsistent results. OBJECTIVE: The current study aimed to evaluate the prevalence of SED and its effect on AD severity and clinical outcomes. METHODS: Patients with AD from Kaohsiung Municipal Ta-tung Hospital were included in this study. International 10-20 system scalp electroencephalography for 13 minutes was performed to detect SED. Clinical outcomes of patients with and without SED were assessed by neuropsychological tests [Cognitive Abilities Screening Instrument (CASI), Mini-Mental State Examination (MMSE), and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB)]. RESULTS: 288 patients (mean age 80.5 years, 60.4% female) were enrolled in this study. Fifty-seven (19.8%) out of 288 patients with AD had SED. The prevalence of SED increased with the severity of cognitive impairment. Compared with patients without SED, those with SED showed significantly greater decline in CASI (-9.32 versus -3.52 points, p = 0.0001) and MMSE (-2.52 versus -1.12 points, p = 0.0042) scores in one year. CONCLUSION: SED may play a significant role in AD progression and is a potential therapeutic target.

Static postural stability and neuropsychological performance after awakening from REM and NREM sleep in patients with chronic insomnia: a randomized, crossover, overnight polysomnography study.

STUDY OBJECTIVES: Chronic insomnia disorder (CID) is a common sleep disorder, with a prevalence ranging from 6%-10% worldwide. Individuals with CID experience more fragmented sleep than healthy control patients do. They awaken frequently during the night and have a higher risk of injury from falling. Awakening from different sleep stages may have different effects on postural stability and waking performance. However, limited research has been conducted on this topic. METHODS: This prospective randomized crossover study was conducted between January 2015 and January 2017. We included 20 adults aged 20-65 years who fulfilled the diagnosis criteria for CID. Participants underwent 2 overnight polysomnography studies with an interval of at least 7 days. They were awakened during either rapid eye movement (REM) sleep or stage N1/N2 sleep alternatively. We compared measurements of static postural stability, vigilance scores, and neuropsychological tests between REM sleep and stage N1/N2 sleep awakening. RESULTS: Polysomnography parameters between the 2 nights were comparable. Participants who were awakened from REM sleep had worse static postural stability than those with stage N1/N2 sleep awakening. Compared with stage N1/N2 sleep awakening, larger mean sway areas of center of pressure (P = .0413) and longer center-of-pressure mean distances (P = .0139) were found in REM sleep awakening. There were no statistically significant differences in vigilance scores or neuropsychological tests between the 2 nights. CONCLUSIONS: REM sleep awakening was associated with worse static postural stability than was stage N1/N2 sleep awakening. No statistically significant differences were found in waking performance in alertness or in neuropsychological tests between stage N1/N2 and REM sleep awakening. CITATION: Yeh W-C, Chuang Y-C, Yen C-W, et al. Static postural stability and neuropsychological performance after awakening from REM and NREM sleep in patients with chronic insomnia: a randomized, crossover, overnight polysomnography study. J Clin Sleep Med. 2022;18(8):1983-1992.

Rapid eye movement sleep reduction in patients with epilepsy: A systematic review and meta-analysis.

BACKGROUND: Compared to healthy controls, adults with epilepsy have a disrupted sleep architecture. Changes in sleep macrostructure may be associated with the refractoriness of epilepsy. However, there is no consensus regarding the changes in sleep architecture in patients with epilepsy. This meta-analysis aimed to elucidate the differences in sleep architecture between patients with epilepsy and healthy controls. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. The PubMed, Embase, and Cochrane Central databases were searched (until May 2021) for studies comparing polysomnographic sleep macrostructures between patients with epilepsy and healthy controls. A meta-analysis was performed using a random-effects model. The percentage of rapid eye movement (REM) sleep, slow-wave sleep (SWS), and sleep efficiency (SE) were compared between patients with epilepsy and healthy controls. RESULTS: Overall, 24 studies involving 789 patients with epilepsy and 599 healthy controls fulfilled the eligibility criteria. Compared to healthy controls, patients with focal epilepsy had decreased REM sleep and SE. Patients with generalised epilepsy had increased SWS and decreased SE. Subgroup analyses focussed on the potential effect of seizure control on sleep architecture. The results revealed that both antiseizure medication (ASM)-untreated and treated patients had decreased SE. ASM treatment may restore REM sleep in patients with generalised epilepsy but not in patients with focal epilepsy. CONCLUSIONS: This meta-analysis revealed statistically significant differences in the sleep macrostructure between patients with epilepsy and healthy controls. There were significant differences in the sleep macrostructure between ASM-untreated patients and healthy controls, which may be an intrinsic change attributable to epilepsy.

Non-rapid eye movement sleep instability in adults with epilepsy: a systematic review and meta-analysis of cyclic alternating pattern.

STUDY OBJECTIVES: Epilepsy is characterized by disrupted sleep architecture. Studies on sleep macro- and microstructure revealed that patients with epilepsy experience disturbed rapid eye movement (REM) sleep; however, no consensus has been reached on non-REM (NREM) sleep changes. Cyclic alternating pattern (CAP) is a marker of sleep instability that occurs only during NREM sleep. This meta-analysis investigated CAP differences between patients with epilepsy and healthy controls. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines in searching PubMed, Embase, and Cochrane Central database for studies comparing polysomnographic sleep microstructures between patients with epilepsy and healthy controls. A meta-analysis using a random-effects model was performed. We compared CAP rates, percentages of phase A1, A2, A3 subtypes, and phase B durations between patients with epilepsy and healthy controls. RESULTS: A total of 11 studies, including 209 patients with epilepsy and 197 healthy controls, fulfilled the eligibility criteria. Compared with healthy controls, patients with epilepsy had significantly increased CAP rates and decreased A1 subtype percentages, and patients with sleep-related epilepsy had increased A3 subtype percentages. Subgroup analyses revealed that antiseizure medications (ASMs) decreased CAP rates and increased phase B durations but did not affect the microstates of phase A in patients with sleep-related epilepsy. CONCLUSIONS: This meta-analysis detected statistically significant differences in CAP parameters between patients with epilepsy and healthy controls. Our findings suggest patients with epilepsy experience NREM sleep instability. ASMs treatment may decrease NREM instability but did not alter the microstates of phase A.

Quantitative evaluation of the microstructure of rapid eye movement sleep in refractory epilepsy: a preliminary study using electroencephalography and heart rate variability analysis.

INTRODUCTION: Patients with epilepsy have a disturbed sleep architecture. Polysomnographic studies have shown that patients with refractory epilepsy have decreased rapid eye movement (REM) sleep and longer REM latency than those with medically controlled epilepsy. However, little is known about the differences in the REM sleep microstructure between these patient groups. METHODS: We conducted a retrospective case-control study of 20 patients with refractory epilepsy (refractory group) and 28 patients with medically controlled epilepsy (medically controlled group). All patients completed sleep questionnaires and underwent overnight in-lab polysomnography. Five-minute electroencephalogram recordings at the C3 and C4 electrodes from each REM sleep were selected for spectral analysis, and 5-min electrocardiogram segments recorded during REM sleep were used for heart rate variability analysis. The groups' scores on the sleep questionnaires, polysomnographic sleep parameters, indices of sleep-related breathing disorders, and REM sleep electroencephalogram spectra were compared. RESULTS: The refractory group had decreased REM sleep (p < 0.001) and longer REM latency (p = 0.0357) than those of the medically controlled group. Moreover, electroencephalogram spectral analysis revealed that the refractory group had decreased absolute beta power (p = 0.0039) and relative beta power (p = 0.0035) as well as increased relative delta power (p = 0.0015) compared with the medically controlled group. CONCLUSIONS: Differences in the polysomnographic macrostructure and REM sleep microstructure between the study groups suggest REM sleep dysregulation in patients with refractory epilepsy.

Exploring factors associated with interictal heart rate variability in patients with medically controlled focal epilepsy.

PURPOSE: Heart rate variability (HRV) reflects the balance between the functional outputs of the sympathetic and parasympathetic nervous systems. It is lower in patients with epilepsy than in the healthy controls. However, HRV has been inadequately studied in different patient subgroups with medically controlled epilepsy. Hence, this study aimed to investigate factors associated with interictal HRV in patients with medically controlled epilepsy. METHODS: This retrospective cohort study included 54 patients (24 males and 30 females) with medically controlled focal epilepsy who only received monotherapy to eliminate the confounding effect of different antiseizure medications (ASMs). Patients with major systemic or psychiatric disorder comorbidities were excluded. For HRV analysis, electroencephalography and 5-minute well-qualified electrocardiogram segment recording were conducted during stage N1 or N2 sleep. In addition, the association between age, gender, seizure onset type, ASMs, and the time domain and frequency-domain HRV measures was analyzed. RESULTS: HRV negatively correlated with advanced age. Patients with focal to bilateral tonic-clonic seizure (FBTCS) had a significantly lower HRV than focal impaired awareness seizures (FIAS). HRV was not associated with any gender and ASMs. CONCLUSIONS: HRV negatively correlated with age, and patients with FBTCS had a decreased HRV. Thus, these patients may have a declining autonomic function. Therefore, different seizure types may carry different risks of autonomic dysfunction in patients with medically controlled focal epilepsy.

The impact of antiseizure medications on polysomnographic parameters: a systematic review and meta-analysis.

BACKGROUND: Oral antiseizure medications (ASMs) are first-line treatments for patients with epilepsy. However, ASMs may alter sleep architecture, adversely affecting patient outcomes. The meta-analysis aimed to elucidate the effect of ASMs on sleep architecture. METHODS: PubMed, Embase, and Cochrane Central database (up to Febrary 2021) were searched for randomized control trials (RCT) with effects of ASMs on polysomnography parameters. A meta-analysis using a random-effects model was performed. We did not set limitation to the participants with underlying diagnosis of epilepsy. RESULTS: Eighteen randomized-controlled trials fulfilled the eligibility criteria. The effects of five main groups of ASMs (sodium channel blockers, calcium channel blockers, GABA enhancers, synaptic vesicle glycoprotein 2A [SV2A] ligand, and broad-spetrum ASMs) on slow-wave sleep (SWS), rapid eye movement (REM) sleep, and sleep efficiency (SE) were analyzed. Compared with placebo, calcium channel blockers and GABA enhancers significantly increased SWS. GABA enhancers also decreased REM sleep percentage, whereas calcium channel blockers significantly increased SE. Sodium channel blockers, SV2A ligand and broad-spectrum ASMs did not affect SWS, REM sleep, or SE. The subgroup analysis revealed that gabapentin, pregabalin, and tiagabine increased the percentage of SWS. Tiagabine also decreased REM sleep, whereas pregabalin increased SE. Finally, levetiracetam did not affect SWS, REM sleep, and SE. CONCLUSIONS: This meta-analysis indicated that ASMs can have a statistically significant effect on sleep parameters; the effect differs between ASMs.

Rapid eye movement sleep disturbance in patients with refractory epilepsy: A polysomnographic study.

OBJECTIVE/BACKGROUND: Patients with epilepsy have disrupted sleep architecture and a higher prevalence of sleep disturbance. Moreover, obstructive sleep apnea (OSA) is more common among patients with refractory epilepsy. Few studies have compared subjective sleep quality, sleep architecture, and prevalence of OSA between patients with refractory epilepsy and those with medically controlled epilepsy. Therefore, this study aimed to evaluate the differences in sleep quality, sleep architecture, and prevalence of OSA between patients with refractory epilepsy and patients with medically controlled epilepsy. PATIENTS: This retrospective case-control study included 38 patients with refractory epilepsy and 96 patients with medically controlled epilepsy. Sleep parameters and indices of sleep-related breathing disorders were recorded by standard in-laboratory polysomnography. The scores from sleep questionnaires on sleep quality and daytime sleepiness were compared between the two groups. RESULTS: Patients with refractory epilepsy versus medically controlled epilepsy had statistically significantly decreased rapid eye movement (REM) sleep (13.5 ± 6.1% vs. 16.2 ± 6.1%) and longer REM latency (152.2 ± 84.1 min vs. 117.2 ± 61.9 min). Further, no differences were found in the prevalence of sleep-related breathing disorders, subjective sleep quality, prevalence of daytime sleepiness, and quality of life. Although not statistically significant, patients with refractory epilepsy have a lower rate of OSA compared with those with medically controlled epilepsy (21.1% vs. 30.2%). CONCLUSIONS: Patients with refractory epilepsy had more disrupted REM sleep regulation than those with medically controlled epilepsy. Although patients with epilepsy have a higher risk of OSA, in this study patients with refractory epilepsy were not susceptible to OSA.

Posterior reversible encephalopathy syndrome with ischemic infarction complicated with intrauterine fetal death: A case report.

RATIONALE: Posterior reversible encephalopathy syndrome (PRES), a rare neurologic disorder, manifests as headache, altered mental status, seizures, visual disturbances, and other focal neurologic signs with typically reversible clinical symptoms and image changes. Although the underlying mechanism remains unknown, a current theory indicates cerebral autoregulation failure as the primary cause. We report a case of PRES with stroke in an adult with intrauterine fetal death (IUFD). PATIENT CONCERNS: A 35-year-old Asian woman with twin pregnancy underwent cesarean section at 32 weeks of gestation because of IUFD. She presented with focal seizures and visual field defect 2 days after undergoing cesarean section. Her blood pressure and kidney, liver, and coagulation functions were normal without proteinuria. DIAGNOSIS: PRES was diagnosed based on a series of brain magnetic resonance imaging findings. Ischemic infarction in the right frontal lobe eventually developed to encephalomalacia. INTERVENTIONS: The patient received levetiracetam and valproate for seizure management. OUTCOMES: Five days after the onset, seizures were under control. All neurologic deficits completely improved after 21 days of admission. LESSONS: PRES can occur in women with IUFD without preeclampsia or eclampsia symptoms. Although most cases result in vasogenic edema of the brain and exhibit good prognosis, PRES can cause cytotoxic edema and permanently damage the brain.