REM sleep behavior disorder: Characteristics of polysomnographic and behavioral manifestations Abstract REM sleep behavior disorder (RBD) is a disease characterized by abnormal motor activity corresponding to the dream content. REM sleep without atonia (RWA) and behavioral manifestations are the main features registered by video-polysomnography (PSG). Because idiopathic RBD (iRBD) is considered as prodromal stage of synucleinopathies, the direction of current research is the search for markers of early conversion. The goal of this study was to observe the group of patients with iRBD with regard to the development of manifest neurodegenerative disease, to find and test a new polysomnographic marker of phenoconversion, to perform analysis of the movements registered by video and to quantify excessive fragmentary myoclonus (EFM), which is a frequent finding in neurodegenerative processes. A total of 55 patients with iRBD were observed for 2.3±0.7 years. The annual conversion rate was 5.5%. Mixed RWA, representing simultaneous occurrence of phasic and tonic RWA, was suggested as a new marker of phenoconversion. Converted patients showed a higher mixed RWA (p=0.009) and the ROC analysis confirmed that mixed RWA is the best predictive marker of conversion among other RWA types (AUC 0.778). An average of...

Indiana University-Purdue University Indianapolis (IUPUI) / Lafora disease is a neurodegenerative disorder caused by mutations in either the EPM2A or the EPM2B gene that encode a glycogen phosphatase, laforin and an E3 ubiquitin ligase, malin, respectively. A hallmark of the disease is accumulation of insoluble, poorly branched, hyperphosphorylated glycogen in brain, muscle and heart. The laforin-malin complex has been proposed to play a role in the regulation of glycogen metabolism and protein degradation/quality control. We evaluated three arms of protein quality control (the autophagolysosomal pathway, the ubiquitin-proteasomal pathway, and ER stress response) in embryonic fibroblasts from Epm2a-/-, Epm2b-/- and Epm2a-/- Epm2b-/- mice. There was an mTOR-dependent impairment in autophagy, decreased proteasomal activity but an uncompromised ER stress response in the knockout cells. These defects may be secondary to the glycogen overaccumulation. The absence of malin, but not laforin, decreased the level of LAMP1, a marker of lysosomes, suggesting a malin function independent of laforin, possibly in lysosomal biogenesis and/or lysosomal glycogen disposal. To understand the physiological role of malin, an unbiased diGly proteomics approach was developed to search for malin substrates. Ubiquitin forms an isopeptide bond with lysine of the protein upon ubiquitination. Proteolysis by trypsin cleaves the C-terminal Arg-Gly-Gly residues in ubiquitin and yields a diGly remnant on the peptides. These diGly peptides were immunoaffinity purified using anti-diGly antibody and then analyzed by mass spectrometry. The mouse skeletal muscle ubiquitylome was studied using diGly proteomics and we identified 244 nonredundant ubiquitination sites in 142 proteins. An approach for differential dimethyl labeling of proteins with diGly immunoaffinity purification was also developed. diGly peptides from skeletal muscle of wild type and Epm2b-/- mice were immunoaffinity purified followed by differential dimethyl labeling and analyzed by mass spectrometry. About 70 proteins were identified that were present in the wild type and absent in the Epm2b-/- muscle tissue. The initial results identified 14 proteins as potential malin substrates, which would need validation in future studies.

In dieser Arbeit kann gezeigt warden, dass mit der kortiko-muskulären und intermuskulären Frequenzanalyse distinkte Koheränzmuster bei verschiedenen Bewegungsstörungen (kortikaler Myoklonus, Extremitätendystonie, Myoklonus bei kortikobasaler Degeneration) identifiziert werden können. Ferner konnte gezeigt werden, dass das retikulospinale System mit der intermuskulären Frequenzanalyse untersucht werden kann, was neue Perspektiven bei der Untersuchung subkortikaler Abschnitte des motorischen Systems ermöglicht. / It can be shown in this work that distinct patterns of cortico-muscular and/or intermuscular coherence can be identfied in a variety of movement disorders (cortical myoclonus, limb dystonia, myoclonus of CBD). Additionally, it could be demonstrated that the assessment of the reticulospinal system is feasible by using intermuscular frequency analysis of homologous muscles, which might open up a new line of research of subcortical drives within the motor system.

INTRODUÇÃO: Os Movimentos Periódicos dos Membros (PLM) são movimentos repetitivos, estereotipados, que ocorrem principalmente nos membros inferiores e associam-se freqüentemente à Síndrome das Pernas Inquietas (SPI), na qual os pacientes relatam necessidade de mover os membros, geralmente associada a desconforto que pode ser exacerbado com a inatividade e piora no fim da tarde ou à noite. PLM são relatados em pacientes com lesão medular, indicando um componente medular da desordem. Neste trabalho, PLM e SPI são analisados em pacientes com lesão medular. MÉTODOS: Neste estudo observacional realizado entre novembro de 2007 e novembro de 2008, comparou-se achados polissonográficos, Escala de Sonolência de Epworth, Questionário de Síndrome das Pernas Inquietas, entre 2 grupos de indivíduos com idade de 18 a 40 anos, sem outros distúrbios de sono: Grupo Controle (GC) e Grupo Lesão Medular (LM). RESULTADOS: LM contou com 9 homens e GC tinha 8 homens e 8 mulheres. Não houve diferença significativa entre as idades de cada grupo: LM com 28 ±7,382 anos e CG com 24,38 ± 4,031 anos. O grupo LM caracterizou-se por 3 lesões cervicais ASIA A, 5 lesões torácicas A e 1 lesão torácica B avaliados através da avaliação American Spinal Cord Injury Association ASIA, com tempo de lesão variando de 1 ano e 1 mês a 5 anos e 2 meses, com mediana de 4, 615 anos; as causas de lesão medular foram acidente de motocicleta (86,44%), mergulho (6,78%) e queda de bicicleta (6,78%). 77,80% de LM apresenta Movimentos Periódicos dos Membros (PLM) em comparação com 31,30% de GC (p=0,04; IC95% = 1,2-51,2). Não houve diferença significativa na gravidade de PLM entre os grupos (p>0,05). Em LM, não houve diferença significativa entre PLM índex NREM e PLM índex REM (p= 0,05). Na avaliação de sonolência, não houve diferença significativa entre os grupos (p>0,05); não houve correlação entre PLM e sonolência excessiva diurna (r= 0,02). LM apresentou 100% de frequência de SPI contra 17% de GC (p < 0,0001). Não houve diferença significativa entre os grupos na gravidade da SPI (p>0,05). Em relação ao número de microdespertares, não houve diferença significativa entre os grupos (p>0,05). Não houve diferença significativa entre os grupos na comparação de eficiência de sono (p>0,05), porém o subgrupo dos tetraplégicos de LM apresentou 9,97±2,17 minutos de tempo de latência enquanto o GC apresentou 3,65±2,43 minutos (p=0,01). CONCLUSÕES: a SPI e o PLM são mais frequentes em lesados medulares que na população em idade de 18 a 40 anos sem outros distúrbios de sono associados, o que pode sugerir que PLM e SPI estejam relacionados ao Centro Gerador de Padrão Medular. / INTRODUCTION: The Periodic Leg Movements (PLM) are repetitive, stereotyped movements that occur mainly in legs and are frequently associated to Restless Legs Syndrome (RLS) in which patients refer the need to move the limbs, usually associated to discomfort that might worse with inactivity and worse in the evening or night. PLM are reported in patients with spinal cord injury thus indicating a spinal component in the disorder. In this research PLM were analyzed in spinal cord injury patients. METHODS: In this observation study performed from November 2007 to November 2008, polysomnographic findings, Epworth Sleepiness Scale Score and an adapted form of International Restless Legs Syndrome Scale Score were compared between 2 groups formed by 18 to 40 years old volunteers without any other sleep disturbances: Control Group (CG) and Spinal Cord Injury Group (SCIG). RESULTS: The SCIG was composed by 9 men and the CG was composed by 8 men and 8 women. There was no statistically significant difference in ages of each group: SCIG 28 ±7,382 years and CG 24,38 ± 4,031 years. The SCGI group was characterized by 3 A cervical spinal cord injury (SCI), 5 A thoracic SCI and 1 B thoracic SCI classified according to American Spinal Cord Injury Association (ASIA) evaluation, presenting from 1 year and 1 month to 5 years and 2 months of injury time, with median of 4,615 years. The SCI were caused by motorcycle accident (86,44%), shallow water diving (6,78%) and bicycle fall (6,78%). In SCIG 77,80% presented PLM while 31,30% presented PLM in CG (p=0,041; CI95% = 1,2-51,2). There wasn´t significant difference in PLM severity between groups (p>0,05). In SCIG there wasn´t significant difference between PLM index NREM and PLM index REM (p>0,05). There wasn´t correlation between PLM and excessive diurnal somnolence (r=0,02). SCGI presented 100% of RLS comparing to 17% in CG (p < 0,0001). There was no significant difference in RLS severity between groups (p>0,05). There was no significant difference in arousal index between groups (p>0,05).There was no significant difference in sleep efficiency (p>0,05), however the subgroup of tetraplegic patients in SCIG presented 9,97±2,17 minutes while CG presented 3,65±2,43 minutes of sleep onset time (p=0,01). CONCLUSIONS: RLS and SPI are more recurrent in SCI patients than in general population from 18 to 40 years old without any other sleep disturbances. This might suggest that PLM and RLS are related to Spinal Cord Central Pattern Generator.

INTRODUÇÃO: Os Movimentos Periódicos dos Membros (PLM) são movimentos repetitivos, estereotipados, que ocorrem principalmente nos membros inferiores e associam-se freqüentemente à Síndrome das Pernas Inquietas (SPI), na qual os pacientes relatam necessidade de mover os membros, geralmente associada a desconforto que pode ser exacerbado com a inatividade e piora no fim da tarde ou à noite. PLM são relatados em pacientes com lesão medular, indicando um componente medular da desordem. Neste trabalho, PLM e SPI são analisados em pacientes com lesão medular. MÉTODOS: Neste estudo observacional realizado entre novembro de 2007 e novembro de 2008, comparou-se achados polissonográficos, Escala de Sonolência de Epworth, Questionário de Síndrome das Pernas Inquietas, entre 2 grupos de indivíduos com idade de 18 a 40 anos, sem outros distúrbios de sono: Grupo Controle (GC) e Grupo Lesão Medular (LM). RESULTADOS: LM contou com 9 homens e GC tinha 8 homens e 8 mulheres. Não houve diferença significativa entre as idades de cada grupo: LM com 28 ±7,382 anos e CG com 24,38 ± 4,031 anos. O grupo LM caracterizou-se por 3 lesões cervicais ASIA A, 5 lesões torácicas A e 1 lesão torácica B avaliados através da avaliação American Spinal Cord Injury Association ASIA, com tempo de lesão variando de 1 ano e 1 mês a 5 anos e 2 meses, com mediana de 4, 615 anos; as causas de lesão medular foram acidente de motocicleta (86,44%), mergulho (6,78%) e queda de bicicleta (6,78%). 77,80% de LM apresenta Movimentos Periódicos dos Membros (PLM) em comparação com 31,30% de GC (p=0,04; IC95% = 1,2-51,2). Não houve diferença significativa na gravidade de PLM entre os grupos (p>0,05). Em LM, não houve diferença significativa entre PLM índex NREM e PLM índex REM (p= 0,05). Na avaliação de sonolência, não houve diferença significativa entre os grupos (p>0,05); não houve correlação entre PLM e sonolência excessiva diurna (r= 0,02). LM apresentou 100% de frequência de SPI contra 17% de GC (p < 0,0001). Não houve diferença significativa entre os grupos na gravidade da SPI (p>0,05). Em relação ao número de microdespertares, não houve diferença significativa entre os grupos (p>0,05). Não houve diferença significativa entre os grupos na comparação de eficiência de sono (p>0,05), porém o subgrupo dos tetraplégicos de LM apresentou 9,97±2,17 minutos de tempo de latência enquanto o GC apresentou 3,65±2,43 minutos (p=0,01). CONCLUSÕES: a SPI e o PLM são mais frequentes em lesados medulares que na população em idade de 18 a 40 anos sem outros distúrbios de sono associados, o que pode sugerir que PLM e SPI estejam relacionados ao Centro Gerador de Padrão Medular. / INTRODUCTION: The Periodic Leg Movements (PLM) are repetitive, stereotyped movements that occur mainly in legs and are frequently associated to Restless Legs Syndrome (RLS) in which patients refer the need to move the limbs, usually associated to discomfort that might worse with inactivity and worse in the evening or night. PLM are reported in patients with spinal cord injury thus indicating a spinal component in the disorder. In this research PLM were analyzed in spinal cord injury patients. METHODS: In this observation study performed from November 2007 to November 2008, polysomnographic findings, Epworth Sleepiness Scale Score and an adapted form of International Restless Legs Syndrome Scale Score were compared between 2 groups formed by 18 to 40 years old volunteers without any other sleep disturbances: Control Group (CG) and Spinal Cord Injury Group (SCIG). RESULTS: The SCIG was composed by 9 men and the CG was composed by 8 men and 8 women. There was no statistically significant difference in ages of each group: SCIG 28 ±7,382 years and CG 24,38 ± 4,031 years. The SCGI group was characterized by 3 A cervical spinal cord injury (SCI), 5 A thoracic SCI and 1 B thoracic SCI classified according to American Spinal Cord Injury Association (ASIA) evaluation, presenting from 1 year and 1 month to 5 years and 2 months of injury time, with median of 4,615 years. The SCI were caused by motorcycle accident (86,44%), shallow water diving (6,78%) and bicycle fall (6,78%). In SCIG 77,80% presented PLM while 31,30% presented PLM in CG (p=0,041; CI95% = 1,2-51,2). There wasn´t significant difference in PLM severity between groups (p>0,05). In SCIG there wasn´t significant difference between PLM index NREM and PLM index REM (p>0,05). There wasn´t correlation between PLM and excessive diurnal somnolence (r=0,02). SCGI presented 100% of RLS comparing to 17% in CG (p < 0,0001). There was no significant difference in RLS severity between groups (p>0,05). There was no significant difference in arousal index between groups (p>0,05).There was no significant difference in sleep efficiency (p>0,05), however the subgroup of tetraplegic patients in SCIG presented 9,97±2,17 minutes while CG presented 3,65±2,43 minutes of sleep onset time (p=0,01). CONCLUSIONS: RLS and SPI are more recurrent in SCI patients than in general population from 18 to 40 years old without any other sleep disturbances. This might suggest that PLM and RLS are related to Spinal Cord Central Pattern Generator.