Wilson?s disease presenting as rapid eye movement sleep behavior disorder: a possible window to early treatment

Abstract

Objective: To describe characteristics of REM sleep behavior disorder in Wilson's disease. Method: Questionnaire-based interviews (patients and relatives), neurological examinations, two-week prospective dream-diary, video-polysomnography, transcranial sonography, MRI. Results: Four Wilson's disease cases with REM sleep behavior disorder were described; three had REM sleep behavior disorder as initial symptom. All showed mesencephalic tegmental/tectal sonographic hyperechogenicities and two presented ponto-mesencephalic tegmental MRI hyperintensities. Conclusion: This first description of REM sleep behavior disorder in Wilson's disease in literature documents REM sleep behavior disorder as a possible presenting symptom of Wilson's disease and adds further evidence to the parallelism of Parkinson's disease and Wilson's disease in phenotype and brainstem topography, which ought to be further studied. REM sleep behavior disorder has prognostic relevance for neurodegeneration in a-synucleinopathies. In Wilson's disease, usefulness of early diagnosis and treatment are already well established. REM sleep behavior disorder in Wilson's disease offers a possible theoretical model for potential early treatment in this extrapyramidal and brainstem paradigm syndrome, previewing the possibility of neuroprotective treatment for REM sleep behavior disorder in "pre-clinical" Parkinson's disease.Keywords: Wilson's disease, parkinsonian syndromes, rapid eye movement sleep behavior disorder, parasomnias, tegmentum. RESUMOObjetivo: Descrever características do transtorno comportamental do sono REM (TCSR) na doença de Wilson (DW). Método: Aplicação de entrevistas, vídeo-polissonografia, sonografia transcraniana (STC), ressonância magnética (RM), diário de sonhos. Resultados: Descrevemos quatro casos de DW com TCSR. Três apresentaram o TCSR como primeira manifestação. Todos mostraram hiperecogenicidades mesencefálicas na STC, dois apresentaram hiperintensidades ponto-mesencefálicas na RM. Conclusão: Esta é a primeira descrição do TCSR na DW. Relatamos o TCSR como um sintoma inicial da DW. Acrescentamos prova para o paralelismo entre a doença de Parkinson e DW, com relação aos fenótipos e localização das lesões cerebrais. Nas alfa-sinucleinopatias, o TCSR tem relevância prognóstica quanto à neurodegeneração. Na DW, já conhecemos a importância de diagnóstico e tratamento precoces. O TCSR na DW oferece um modelo para antecipar o tratamento desta síndrome de acometimento dos núcleos basais e tronco, vislumbrando a possibilidade de tratamento neuroprotetor para a fase "pré-clínica" da DP.Palavras-chave: doença de Wilson, síndromes parkinsonianas, transtorno comportamental do sono REM, parassonias, tegmento.Wilson's disease (WD) causes tissue copper storage, especially in brain, cornea, and liver. Early stages of metal deposits in basal ganglia and brainstem in WD may be detected by transcranial sonography (TCS) 1 . WD's patients frequently suffer from disorders of sleep 2,3,4 , including altered REM sleep 2 , nevertheless REM slee...

Wilson's disease with and without rapid eye movement sleep behavior disorder compared to healthy matched controls

“…Nevertheless, these estimations were confirmed by the mothers of all five patients with RBD. Repeat MRIs documented an almost complete disappearance of pontine and mesencephalic tegmental lesions in our trientine treated male patient with RBD [15]. This morphologic development was chronologically paralleled, to a large extent, by the evolution from an initially severe expression of RBD to an eventual …”

“…This study was performed to: (1) further characterize sleep and sleep disturbances in WD as compared to healthy subjects, (2) evaluate the possible existence of RWA and RBD in WD, and (3), inasmuch present, characterize and quantify neurological and somnological features of RBD in WD as compared to WD without RBD and to healthy controls. Preliminary data of four cases of this cohort have been published [15].…”

Rapid Eye Movement Sleep Behavior Disorder: Overview and Current Perspective

“…In contrast to alphasynuclein disorders, it is not a precursor in these conditions but occurs either coincidental or subsequent to development of other neurological symptoms [43]. Table 1 enlists various disorders such as amyloidopathies, tauopathies, TDP-43 proteinopathies, tri/tetranucleotide repeat disorders, genetic, congenital, and developmental conditions which have been reported to occur with RBD although at a much lower frequency [3,[44][45][46][47]. The one exception is spinocerebellar ataxia type 3 (SCA3), a trinucleotide repeat disorder of cerebellar and brainstem degeneration.…”

Dream Recall Frequencies and Dream Content in Wilson’s Disease with and without REM Sleep Behaviour Disorder: A Neurooneirologic Study

“…On the other hand, in some movement disorder conditions, physical motor disability has been shown to affect dream content very little [ 12 , 13 ], as these patients generally dream of themselves without limitations of their movement abilities. In addition, RBD has been recently described also in WD [ 14 ]. Polysomnography parameters and sleep quality have been shown to be significantly worse in WD, both with and without RBD, as compared to healthy controls [ 15 ].…”