Uma origem subcortical para os movimentos periódicos dos membros no sono (MPMS) é apoiada pela ausência de potenciais de eletroencefalograma cerebral no início dos movimentos dos membros detectados por eletromiografia (EMG) durante a polissonografia.[7]Rijsman RM, Stam CJ, de Weerd AW. Abnormal H-reflexes in periodic limb movement disorder: impact on understanding the pathophysiology of the disorder. Clin Neurophysiol. 2005;116:204-210.
http://www.ncbi.nlm.nih.gov/pubmed/15589198?tool=bestpractice.com
[18]Vetrugno R, Provini F, Plazzi G, et al. Propriospinal myoclonus: a motor phenomenon found in restless legs syndrome different from periodic limb movements during sleep. Mov Disord. 2005; 20:1323-1329.
http://www.ncbi.nlm.nih.gov/pubmed/16007657?tool=bestpractice.com
[19]Lee MS, Choi YC, Lee SH, et al. Sleep-related periodic leg movements associated with spinal cord lesions. Mov Disord. 1996;11:719-722.
http://www.ncbi.nlm.nih.gov/pubmed/8914100?tool=bestpractice.com
[20]Lee MS, Lyoo CH, Kim WC, et al. Periodic bursts of rhythmic dyskinesia associated with spinal anesthesia. Mov Disord. 1997;12:816-817.
http://www.ncbi.nlm.nih.gov/pubmed/9380075?tool=bestpractice.com
[21]Bucher SF, Seeleos KC, Oertel WH, et al. Cerebral generators involved in the pathogenesis of the restless legs syndrome. Ann Neurol. 1997;41:639-645.
http://www.ncbi.nlm.nih.gov/pubmed/9153526?tool=bestpractice.com
[22]Bara-Jimenez W, Aksu M, Graham B, et al. Periodic limb movements in sleep: state-dependent excitability of the spinal flexor reflex. Neurology. 2000;54:1609-1616.
http://www.ncbi.nlm.nih.gov/pubmed/10762502?tool=bestpractice.com
A análise por EMG dos MPMS sugere um padrão de propagação atribuível às vias proprioespinhais, com a atividade motora se iniciando em músculos, como o quadríceps femoral, antes de se disseminar para a outra perna e os músculos axiais.[7]Rijsman RM, Stam CJ, de Weerd AW. Abnormal H-reflexes in periodic limb movement disorder: impact on understanding the pathophysiology of the disorder. Clin Neurophysiol. 2005;116:204-210.
http://www.ncbi.nlm.nih.gov/pubmed/15589198?tool=bestpractice.com
[18]Vetrugno R, Provini F, Plazzi G, et al. Propriospinal myoclonus: a motor phenomenon found in restless legs syndrome different from periodic limb movements during sleep. Mov Disord. 2005; 20:1323-1329.
http://www.ncbi.nlm.nih.gov/pubmed/16007657?tool=bestpractice.com
[19]Lee MS, Choi YC, Lee SH, et al. Sleep-related periodic leg movements associated with spinal cord lesions. Mov Disord. 1996;11:719-722.
http://www.ncbi.nlm.nih.gov/pubmed/8914100?tool=bestpractice.com
[20]Lee MS, Lyoo CH, Kim WC, et al. Periodic bursts of rhythmic dyskinesia associated with spinal anesthesia. Mov Disord. 1997;12:816-817.
http://www.ncbi.nlm.nih.gov/pubmed/9380075?tool=bestpractice.com
[21]Bucher SF, Seeleos KC, Oertel WH, et al. Cerebral generators involved in the pathogenesis of the restless legs syndrome. Ann Neurol. 1997;41:639-645.
http://www.ncbi.nlm.nih.gov/pubmed/9153526?tool=bestpractice.com
[22]Bara-Jimenez W, Aksu M, Graham B, et al. Periodic limb movements in sleep: state-dependent excitability of the spinal flexor reflex. Neurology. 2000;54:1609-1616.
http://www.ncbi.nlm.nih.gov/pubmed/10762502?tool=bestpractice.com
MPMS foram relatados distalmente a transecções completas da medula espinhal, e são observados durante a indução de anestesia espinhal.[20]Lee MS, Lyoo CH, Kim WC, et al. Periodic bursts of rhythmic dyskinesia associated with spinal anesthesia. Mov Disord. 1997;12:816-817.
http://www.ncbi.nlm.nih.gov/pubmed/9380075?tool=bestpractice.com
Essas observações induziram a sugestão de que MPMS são gerados na medula espinhal e surgem da ativação de diversos geradores medulares centrais não sincronizados.[20]Lee MS, Lyoo CH, Kim WC, et al. Periodic bursts of rhythmic dyskinesia associated with spinal anesthesia. Mov Disord. 1997;12:816-817.
http://www.ncbi.nlm.nih.gov/pubmed/9380075?tool=bestpractice.com
[22]Bara-Jimenez W, Aksu M, Graham B, et al. Periodic limb movements in sleep: state-dependent excitability of the spinal flexor reflex. Neurology. 2000;54:1609-1616.
http://www.ncbi.nlm.nih.gov/pubmed/10762502?tool=bestpractice.com
Tem-se sugerido também que os MPMS podem ser modulados por influências supraespinhais descendentes, potencialmente surgindo do sistema reticular do tronco encefálico.[7]Rijsman RM, Stam CJ, de Weerd AW. Abnormal H-reflexes in periodic limb movement disorder: impact on understanding the pathophysiology of the disorder. Clin Neurophysiol. 2005;116:204-210.
http://www.ncbi.nlm.nih.gov/pubmed/15589198?tool=bestpractice.com
[18]Vetrugno R, Provini F, Plazzi G, et al. Propriospinal myoclonus: a motor phenomenon found in restless legs syndrome different from periodic limb movements during sleep. Mov Disord. 2005; 20:1323-1329.
http://www.ncbi.nlm.nih.gov/pubmed/16007657?tool=bestpractice.com
[19]Lee MS, Choi YC, Lee SH, et al. Sleep-related periodic leg movements associated with spinal cord lesions. Mov Disord. 1996;11:719-722.
http://www.ncbi.nlm.nih.gov/pubmed/8914100?tool=bestpractice.com
[20]Lee MS, Lyoo CH, Kim WC, et al. Periodic bursts of rhythmic dyskinesia associated with spinal anesthesia. Mov Disord. 1997;12:816-817.
http://www.ncbi.nlm.nih.gov/pubmed/9380075?tool=bestpractice.com
[21]Bucher SF, Seeleos KC, Oertel WH, et al. Cerebral generators involved in the pathogenesis of the restless legs syndrome. Ann Neurol. 1997;41:639-645.
http://www.ncbi.nlm.nih.gov/pubmed/9153526?tool=bestpractice.com
[22]Bara-Jimenez W, Aksu M, Graham B, et al. Periodic limb movements in sleep: state-dependent excitability of the spinal flexor reflex. Neurology. 2000;54:1609-1616.
http://www.ncbi.nlm.nih.gov/pubmed/10762502?tool=bestpractice.com
Essa hipótese recebeu algum apoio de estudos funcionais por RNM envolvendo regiões dopaminérgicas do tronco encefálico nos MPMS.[25]Cervenka S, Palhagen SE, Comley RA, et al. Support for dopaminergic hypoactivity in restless legs syndrome: a PET study on D2-receptor binding. Brain. 2006;129:2017-2028.
http://brain.oxfordjournals.org/content/129/8/2017.full
http://www.ncbi.nlm.nih.gov/pubmed/16816393?tool=bestpractice.com
A hipoatividade dopaminérgica foi postulada como um mecanismo para MPMS associados à síndrome das pernas inquietas, com uma redução na transmissão dopaminérgica potencialmente exacerbada por baixos níveis de ferro.[23]Allen R. Dopamine and iron in the pathophysiology of restless legs syndrome (RLS). Sleep Med. 2004;5:385-391.
http://www.ncbi.nlm.nih.gov/pubmed/15222997?tool=bestpractice.com
[24]Clemens S, Rye D, Hochman S. Restless legs syndrome: revisiting the dopamine hypothesis from the spinal cord perspective. Neurology. 2006;67:125-130.
http://www.ncbi.nlm.nih.gov/pubmed/16832090?tool=bestpractice.com
[25]Cervenka S, Palhagen SE, Comley RA, et al. Support for dopaminergic hypoactivity in restless legs syndrome: a PET study on D2-receptor binding. Brain. 2006;129:2017-2028.
http://brain.oxfordjournals.org/content/129/8/2017.full
http://www.ncbi.nlm.nih.gov/pubmed/16816393?tool=bestpractice.com
O benefício sintomático proporcionado por opiáceos conduziu a teorias que postulam que os MPMS podem ser resultantes de um distúrbio no equilíbrio da absorção de dopamina-opiáceos aos neurotransmissores que medeiam as ações motoras e a percepção da dor.