Periodic limb movements during sleep vs seizures and epileptiform discharges: some supposedly shared pathomechanisms / Movimentos periódicos dos membros durante o sono vs crises e descargas epileptiformes: alguns patomecanismos supostamente compartilhados

This is a narrative review that assesses some possible underlying abnormal mechanisms shared between periodic limb movements during sleep (PLMS) and interictal epileptiform discharges (IEDs) or epileptic seizures. The underlying abnormal mechanisms of PLMS are not clearly defined, but the hypotheses raised include a pure motor mechanism originating in the brainstem, spinal cord or a cortico-subcortical interaction, influenced by predisposing factors, through neural networks. PLMS rhythmicity appears to be closely linked to sleep microarchitecture, and also to cortical arousals, as with some types of epilepsy, which involve both the underlying sleep rhythms and their intrinsic functions as well as the so-called central pattern generators that produce rhythmic motor patterns. However, the relationship between PLMS and epilepsy has not yet been fully clarified. Rhythmicity and sleep fragmentation appear to be common denominators between them, at least more closely in sleep-related hypermotor epilepsy. To some extent, the electroencephalographic changes of PLMS would express an epiphenomenon of the involvement of some underlying brain networks common to epileptic seizures and IEDs.

Esta é uma revisão narrativa que avalia alguns possíveis mecanismos anormais subjacentes compartilhados entre os movimentos periódicos dos membros durante o sono (MPMS) e as descargas epileptiformes interictais (DEIs) ou crises epilépticas. Os mecanismos anormais subjacentes dos MPMS não estão claramente definidos, mas as hipóteses levantadas incluem mecanismo motor puro originado no tronco cerebral, medula espinhal ou uma interação córtico-subcortical, por influência de fatores predisponentes, através das redes neurais. A ritmicidade dos MPMS aparece estar intimamente ligada à microarquitetura do sono, e também aos despertares corticais, como acontece com alguns tipos de epilepsia, o que envolve tanto os ritmos subjacentes do sono e suas funções intrínsecas quanto os chamados geradores de padrões centrais que produzem padrões motores rítmicos. No entanto, a relação entre PLMS e epilepsia ainda não foi totalmente esclarecida. Ritmicidade e fragmentação do sono parecem ser denominadores comuns entre eles, pelo menos mais intimamente na epilepsia hipermotora relacionada ao sono. Em certa medida, as alterações eletroencefalográficas de PLMS expressariam um epifenômeno do envolvimento de algumas redes cerebrais subjacentes comuns a crises epilépticas e IEDs.

Preliminary clinical analysis for acute cerebral infarction with periodic limb movements / 中国脑血管病杂志

Objective To analyze the clinical features of patients with acute cerebral infarction combined with periodic limb movements during sleep (PLMS). Methods A total of 170 continuous patients with acute cerebral infarction in the Department of Neurology of the Second Affiliated Hospital of Soochow University from February 2016 to June 2018 was enrolled prospectively, including 102 males (60. 0%) and 68 females(40. 0%). Those patients were divided into non-PLMS group (period limb movement index[PLMI] 0. 05). (2) In the non-PLMS group, the proportion of partial anterior circulation infarction was the highest (34. 8%, 23/66), and the proportion of complete anterior circulation infarction was the lowest (10. 6%, 7/66). In the PLMS group, the proportion of lacunar infarction was the highest (36.5 %, 38/104), and the proportion of complete anterior circulation infarction was the lowest (8.7%, 9/104). There was statistically significant in stroke classification of OCSP between the two groups (χ2=12.528, P=0.006), but insignificant in fasting blood glucose, glycated hemoglobin, creatinine, homocysteine, total cholesterol and low-density lipoprotein levels between the two groups (both P > 0. 05). (3) The proportion of awakening, awakening time, and the number of awakenings in the non-PLMS group were all lower than those in the PLMS group, which were statistically significant (6.0[3.0, 8.0] vs. 12.0[7. 0, 19.0], 3.0[1.5, 4.2] min vs. 4.4[3.0, 6.0] min and 18.5[7.0, 33.8] times vs.50.0[28.0, 84.0] times, the Z values were -6.046, -3.922 and -6.8789, all P 0. 05). Conclusions Patients with acute cerebral infarction have a high proportion of PLMS in the acute phase. There is a high proportion of lacunar infarction and sleep fragmentation in patients with acute cerebral infarction combined with PLMS.

Síndrome de piernas inquietas en niños: caracterización clínica / Characterization of restless leg syndrome in children

El Síndrome de piernas inquietas (SPI) o Enfermedad de Willis­Ekbom, es una condición neurológica que afecta al 2-4% de los niños en edad escolar. Etiológicamente se ha relacionado al metabolismo del hierro y a factores genéticos entre otros. En niños aun es una patología poco diagnosticada. Trabajo observacional descriptivo, en el cual se realiza caracterización clínica, según criterios internacionales, en 14 pacientes menores de 18 años, 9 varones. Edad promedio 8 años. Sintomatología inicial variada, desde resistencia a ir a la cama, hasta dibujar sus molestias. En 10 se comprobó déficit de hierro. En 11 pacientes se realizó un polisomnograma, 10 de ellos con un índice elevado de movimientos periódicos de extremidades. El uso de pregabalina y aporte de hierro fue el tratamiento más utilizado. Dos pacientes tenían padres diagnosticados con SPI.

Abstract. The Restless Legs Syndrome (RLS) or Willis-Ekbom Disease is a neurological condition that affects 2-4% of school-age children. Its etiology has been related to the metabolism of iron and genetic factors among others. In children it is still a frequently undiagnosed disorder. This is a descriptive observational report, in which clinical characterization is carried out according to international criteria in 14 patients under 18 years old, 9 boys. Average age is 8 years old. The initial symptomatology was varied, from resistance to comply with bedtime, to drawing their discomfort. In 9, iron deficiency was found. A polysomnogram was performed in 11 patients, 10 of which had a high periodic limb movements index. The use of pregabalin and supplementary iron were the most used treatments. Two patients had parents diagnosed with RLS.

Decreased Nocturnal Blood Pressure Dipping in Patients with Periodic Limb Movements in Sleep / 수면정신생리

OBJECTIVES: Previous studies have shown that periodic limb movements in sleep (PLMS) could be one of risk factors for cardiovascular morbidity. The purpose of this study was to investigate the association between PLMS and blood pressure changes during sleep. METHODS: We analyzed data from 358 adults (176 men and 182 women) aged 18 years and older who were free from sleep apnea syndrome (Respiratory Disturbance Index 15)]. Blood pressure change patterns were compared using repeated measures analysis of variance. RESULTS: Systolic blood pressure in the high PLMI group was lower than that in the low PLMI group (p = 0.036). These results were also significant when adjusted for gender and age, but were not statistically significant when adjusted for BMI, alcohol, smoking, anti-hypertension medication use and sleep efficiency (p = 0.098). Systolic blood pressure dropped by 9.7 mm Hg in the low PLMI group, and systolic blood pressure in the high PLMI group dropped by 2.9 mm Hg. There was a significant difference in delta systolic blood pressure after sleep between the two groups in women when adjusted for age, BMI, alcohol, smoking, antihypertensive medication use and sleep efficiency (p = 0.023). CONCLUSION: PLMS was significantly associated with a decreasing pattern in nocturnal BP during sleep, and this association remained significant in women when adjusted for age, BMI, alcohol, smoking, antihypertension medication use and sleep efficiency related to blood pressure. We suggest that PLMS may be associated with cardiovascular morbidity.

Periodic Limb Movements in Sleep is Associated with Increased Mortality

OBJECTIVE: To elucidate the association between periodic limb movements in sleep (PLMS) and mortality. METHODS: Nocturnal polysomnographic recordings of 1,344 subjects obtained from 1995 to 2008 were reviewed. The subjects were divided into four groups based on PLMS and insomnia: reference group (PLMS≤5), insomnia group (PLMS≤5 with insomnia symptoms), 515 group. We searched each subject's Identification Number in the death records from the Statistics of Korea, the national bureau of statistics, to determine deaths in the cohort that occurred prior to December, 2013. Cox-proportional hazard regression and Kaplan-Meier survival curve analyses were used to compare mortality among the four groups. RESULTS: Hazard ratios (HRs) in the 515 groups were significantly higher than that in the reference group before adjusting for age and gender [HR, 3.37; 95% confidence interval (CI), 1.73–6.55; p15 group had a higher mortality rate than that in the reference group after adjusting for age, gender, and sleep efficiency (HR, 1.99; 95% CI, 1.06–2.21; p=0.033). CONCLUSION: These results suggest that PLMS may be associated with increased mortality.

The Changes in Polysomnographic Sleep Variables by Periodic Limb Movements During Sleep / 수면정신생리

OBJECTIVES: Periodic limb movement disorder (PLMD) has been debated with regard to its clinical significance and diagnostic criteria. The current diagnostic criterion for PLMD in adults has been changed from periodic limb movement index (PLMI) > 5/ hour to PLMI > 15/hour by the International Classification of Sleep Disorders (ICSD). In this study, we aimed to investigate the changes in polysomnographic sleep variables according to PLMI and to determine the relevance of the diagnostic criterion for PLMD. METHODS: Out of 4195 subjects who underwent standard polysomnography, we selected 666 subjects (370 males and 296 females, aged 47.1 ± 14.8) who were older than 17 years and were not diagnosed with primary insomnia, sleep apnea, narcolepsy, or REM sleep behavior disorder. Subjects were divided into three groups according to PLMI severity: group 1 (PLMI ≤ 5), group 2 (5 15). Demographic and polysomnographic sleep variables and Epworth sleepiness scale (ESS) were compared among the three groups. RESULTS: There were significant differences among the three groups in age and gender. Sleep efficiency (SE) and stage 3 sleep percentage in group 1 were significantly higher than those in groups 2 and 3. The wake after sleep onset (WASO) score in group 1 was significantly lower than those in groups 2 and 3. However, there were no significant differences in SE, stage 3 sleep percentage, or WASO between groups 2 and 3. Sleep latency (SL) in group 1 was significantly lower than that in group 3, but there was no difference in SL between group 2 and group 3. ESS score in group 1 was significantly higher than that in group 3, but there was no difference between group 2 and group 3. Partial correlation analysis adjusted by age showed that PLMI was significantly related to SE and WASO. CONCLUSION: This study suggests that PLMI influences polysomnographic sleep variables. In addition, we found the individuals who did not have PLMD but had PLMI > 5 were not different in polysomnographic sleep variables from the individuals who had PLMD according to the current criterion. These results raise questions about the relevance of the current diagnostic criterion of PLMD.

Clinical Characteristics and Pathophysiological Features of Restless Legs Syndrome (RLS): Recent Advances and Future Challenges.

Restless Legs Syndrome (RLS)/Willi’s-Ekbom disease (WED) or Jimmy Legs is a neurological sensory-motor disorder that causes intense restlessness and unpleasant creepy-crawly feelings inside the lower legs at rest. It can be primary (idiopathic) or secondary (symptomatic) and affects 7-10% of general population with a significant female predominance. RLS is generally associated with conditions like iron deficiency, low serum ferritin levels, pregnancy, menopause, chronic renal disease, diabetes mellitus, cardiovascular disease, Parkinson’s disease and rheumatoid arthritis etc, however, the relationship is not completely understood. In this review, I discussed recent developments on epidemiology, etiology, pathogenesis, diagnosis and clinical management of RLS.

Sleep disorders frequency in post-polio syndrome patients caused by periodic limb movements / Frequência de transtornos do sono em pacientes com síndrome pós-pólio causados por movimentos periódicos dos membros

Post-polio syndrome (PPS) in individuals with polio longer than 15 years is characterized by weakness and/or muscle fatigue, deficit of deglutition and breath and periodic limb movements (PLM) during sleep. We undertook a review of 99 patients with PPS, and assessed the frequency of PLM through polysomnographic recordings at our sleep disorders unit. The total number of PLM, total time of sleep (TTS), efficiency of sleep (EfS), awaking index (AI) and apnea-hypopnea index (AHI) were analyzed. Sixteen patients presented PLM in excess of 5 for the entire night. When comparing these with the group without PLM, a correlation was found (p=0.001). Significant difference was found for the correlation of the parameters: IAH, ID, TTS and EfS when compared the two groups. There is a close relationship between PPS and PLM.

A síndrome pós-pólio (SPP) se manifesta em indivíduos que tiveram poliomielite, após 15 anos ou mais. Caracteriza-se por fraqueza e/ou fadiga muscular, déficit de deglutição e respiração e movimentos periódicos dos membros (PLM) no sono. Identificou-se a freqüência de PLM no sono em 99 polissonografias de pacientes com SPP, atendidos no ambulatório da Universidade Federal de São Paulo/ Escola Paulista de Medicina. Analisou-se número total de PLM, tempo total de sono (TTS), eficiência do sono (EfS), índice de despertar (ID) e índice de apnéia-hipopnéia (IAH). Dezesseis pacientes apresentaram nº de PLM maior que 5 para a noite inteira. Não foi encontrada diferença significativa para a correlação dos parâmetros: índice de apnéia e hipopnéia, índice de despertar, tempo total de sono e eficiência do sono quando comparados os dois grupos. Portanto, considera-se a existência de uma relação entre a presença de PLM e a SPP.

Overview of Periodic Limb Movements During Sleep / 수면정신생리

Periodic leg movements during sleep (PLMS) are best described as repetitive stereotypical movements of the lower extremities characterized by dorsiflexion of the ankle, dorsiflexion of the toes and a partial flexion of the knee and sometimes the hip. The prevalence of PLMS is about 5-11% in adults and is predicted much higher than previously surveyed. They are also frequently found in various sleep disorders, several disorders not primarily affecting sleep, and patients taking psychiatric medications. Although they are rarely found in children, they are common findings in children referred to a pediatric sleep laboratory. The pathophysiology is strongly associated with decline of central dopaminergic function and closely related to arousal system during sleep. Benzodiazepines, levodopa, dopamine agonists and opioids are generally recommended for treatment but more controlled studies on the effectiveness are needed.

Síndrome das pernas inquietas: o que todo médico deve saber / Restless legs syndrome: what every physician should know

A síndrome das pernas inquietas é uma neuropatia causadora de relevante deterioração da qualidade devida nos pacientes acometidos. É conhecida desde a década de 40, mas somente nos últimos anos tem sidoamplamente investigada. Trabalhos recentes têm apontado a importância da história familiar na incidência eno prognóstico da doença, e alguns genes envolvidos já foram identificados. Embora a fisiopatogenia não estejatotalmente elucidada, sabe-se que deficiência de ferro e alterações das vias dopaminérgicas são a basepara o desenvolvimento do quadro. A síndrome das pernas inquietas é caracterizada por sintomas subjetivosde desconforto, principalmente em membros inferiores, acompanhada da urgência em movimentar as regiõesacometidas com relativa atenuação dos sintomas com a movimentação. Por se manifestar predominantementeao fim do dia, nos períodos de repouso e inatividade, o quadro resulta em má qualidade do sono e sonolênciaexcessiva diurna. A gravidade desse quadro é amplamente variável no tempo e no espaço. O diagnóstico éessencialmente clínico. As investigações laboratoriais geralmente são usadas para confirmação da causa. Asopções terapêuticas mostram os agentes dopaminérgicos como a classe mais eficiente de medicamentos, masse podem incluir opiáceos ou benzodiazepínicos em certos casos. Há muitas questões a respeito do mecanismoe do tratamento da síndrome das pernas inquietas, que demandam estudos mais consistentes

The restless legs syndrome is a neurological disorder responsible for reduced quality of life secondary to sleep deterioration. It has been described in the 40?s, but only recently more extensively investigated. The role playedby familiar history has only recently been identified with the determination of some possibly implicated genes.Although its physiopathology has not yet been completely elucidated, it seems possible that iron metabolism anddopaminergic mechanisms form the physiologic basis for understanding this disorder temporal development. Themain features of restless legs syndrome are urging to move the limbs often associated to subjective discomfortsensations, improved by moving or fidgeting. There is a circadian worsening with the symptoms increasing duringthe day and with inactivity, not uncommonly resulting in a bad sleep?s night and daytime sleepiness. The severityof restless legs syndrome symptoms varies in time and space. The diagnostic is essentially clinical. Laboratorywork up is mostly used for etiological confirmation. Therapeutic options show dopaminergic agents as the mostefficient drug class, but it can also include opiates or benzodiazepines in certain cases. There are many openquestions concerning restless legs syndrome mechanisms and treatment options that need to be addressed byconsistent research trials.

Actigraphic Evaluation of Treatment Responses in Periodic Limb Movements in Sleep Patient: Case Study / 수면정신생리

Periodic limb movements in sleep (PLMS) have been diagnosed easily by nocturnal polysomnography (NPSG) and treated effectively with dopamine receptor agonist, benzodiazepine and opioid. However, few reports have objectively assessed the treatment responses. We treated a PLMS patient with clonazepam and pramipexole, and evaluated their efficacy with actigraphy. Clonazepam improved sleep quality without reducing frequency of limb movements, and pramipexole reduced frequency of limb movements without improving sleep quality, results which are consistent with previous study findings. Actigraphy proved useful in evaluation of treatment response of PLMS.

Spectral Analysis of Hidden EEG Arousal Activity in Periodic Leg Movements in Sleep without Microarousal / 수면정신생리

OBJECTIVES: Periodic leg movements in sleep (PLMS) might be subdivided based upon whether or not they are associated with visible EEG microarousals (MA). MA is considered to be responsible for nonrestorative sleep and daytime fatigue. The American Sleep Disorders Association's (ASDA) scoring rules for MA based on visual analysis of the EEG changes suggest that MA should last more than 3 seconds. However, it has been suggested that visual analysis may not detect some changes in EEG activity. This study is aimed at measuring changes in EEG spectra during PLMS without MA in order to better understand the arousing response of PLMS. METHODS: Ten drug-free patients (three men and seven women) diagnosed with PLMS by polysomnography were studied. Spectral analysis of the EEG was performed in each patient on 30 episodes of PLMS without MA, chosen randomly across the night in stage 2 non-REM sleep. We applied stricter criteria for MA compared to ASDA, by defining it as a return to alpha and theta frequency lasting at least 1 second. RESULTS: The mean PLMS index was 16.7 10.0. The mean PLMS duration was 1.3 0.7 seconds. Comparison of 4-second EEG activity both before and after the onset of PLMS without MA using independent t-test showed that the movements were associated with significant increase of relative activity in the delta band (p=0.000) and significant decrease of activity in the alpha (p=0.01) and sigma (p=0.000) bands. No significant decrease in the theta (p=0.05), beta (p=0.129), or gamma (p=0.062) bands was found. CONCLUSIONS: PLMS without MA was found to be associated with EEG change characterized by increase in the delta frequency band. This finding seems to be compatible with the hypothesis of an integrative hierarchy of arousal responses of Sforza's. Considering that the subjects had lower PLMS index and shorter PLMS duration than those of the previous study, it is suggested that an even less severe form of PLMS without MA could induce neurophysiologic change, which may potentially be of clinical significance.

The Comorbidity of Periodic Limb Movements Disorder in Patients with Sleep-Related Breathing Disorder / 결핵

BACKGROUND: Sleep-related breathing disorders(SRBD) and periodic leg movements disorder(PLMD) are both common, and are considered as separate sleep disorders. However, both disorders show high comorbidity. SRBD and PLMD can result in excessive daytime sleepiness and insomnia due to frequent sleep fragmentation So, it is very important to consider the presence of PLMD, when we are dealing with the diagnosis and management of SRBD. The objectives of this study were to determine the incidence of PLMD in patients with SRBD, and 13 describe any differences between patients with and without PLMD. METHOD: The authors reviewed the sleep recordings of 106 Patients with a final diagnosis of SRBD(obstruclive sleep apnea or upper airway resistance syndrome), who underwent full nocturnal polysomnography, including the monitoring of the anterior tibialis electromyogram. All sleep records were recorded and scored using the standard criteria. The data was analyzed by the student t-test. RESULTS: 106 patients(M=76, F=30) were included in the analysis. Data revealed a mean age of 49.5 +/- 13.6 years, a respiratory disturbance index(RDI) of 22.3 +/- 25.4/hour sleep, a lowest oxygen saturation of 84.9 +/- 11.3%, a mammal esophageal pressure of -41.0 +/- 19.1cm H2O, and PLM index(PLMI) index(PLMI) 13.1 +/- 22.4 movements/ hour sleep. Forty four percent(47 of 106 patients) had a PLMI of greater than 5 on this study. The mean age of the patients with PLMD was significantly higher than that of the patients without PLMD(p < 0.005). Fe-male patients with SRBD accompanied more PLMD(p < 0.05). The apnea index of the patients with PLMD was significantly lower than that of the patients without PLMD(p < 0.01). The percentage of stage 1 sleep in the patients with PLMD was significantly lower than that of the patients without PLMD(p < 0.05). CONCLUSION: The prevalence of PLMD in the patients with SRBD was high at 44.3%. The patients with PLMD were older and had more high RDI in comparison to the patients without PLMD, which was consistent with previous findings. The authors recommend that more careful consideration of PLMD is required when diagnosing and treating SRBD.