Quantitative transcranial sonography in Wilson's disease and healthy controls: Cut-off values and functional correlates.

To compare transcranial sonography (TCS) findings in patients with predominantly neurological Wilson's disease (WD) to those from controls, and to correlate TCS data with the clinical profile of WD. Patients with WD (n=40/f=18) and healthy, matched controls (n=49/f=20) were assessed in terms of TCS, serum copper and iron parameters, and clinical scales, such as the Unified Wilson's Disease Rating Scale (UWDRS), Addenbrooke's Cognitive Examination-Revised (ACE-R), Mini Mental State Examination (MMSE), and Beck Depression Inventory. Lenticular nuclei and substantia nigra echogenic area cut-off values clearly differentiated WD patients from controls (area under the curve: 95.4% and 79.4%). Substantia nigra echogenic area was significantly larger in male than in female patients (p=0.001). Compared with controls, patients showed hyperechogenicity also in thalami and midbrain tegmentum/tectum; third ventricle width was increased and midbrain axial area was reduced. In the WD group, male gender correlated with substantia nigra echogenic area (r=0.515, p=0.0007) and serum ferritin levels (r=0.479, p=0.002); lenticular nuclei hyperechogenicity correlated with dystonia (r=0.326, p=0.04) and dysarthria (r=0.334, p=0.035); third ventricle width correlated with dystonia (r=0.439 p=0.005), dysarthria (r=0.449, p=0.004), parkinsonism (r=0.527, p<0.001), UWDRS neurological and total scores (both r=0.504, p=0.0009), MMSE (r=-0.496, p=0.001), and ACE-R (r=-0.534, p=0.0004). Lenticular nuclei echogenic area allowed highly accurate discrimination between patients and controls. The gender differences in substantia nigra echogenicity and iron metabolism are of interest in further studies in WD. TCS reflects different dimensions of WD pathology clearly differentiable from healthy controls and correlating with various clinical characteristics of WD.

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

Objective. Violent dream content and its acting out during rapid eye movement sleep are considered distinctive for rapid eye movement sleep behaviour disorder (RBD). This study reports first quantitative data on dreaming in a cohort of patients with treated Wilson's disease (WD) and in patients with WD with RBD. Methods. Retrospective questionnaires on different dimensions of dreaming and a prospective two-week home dream diary with self-rating of emotions and blinded, categorical rating of content by an external judge. Results. WD patients showed a significantly lower dream word count and very few other differences in dream characteristics compared to age- and sex-matched healthy controls. Compared to WD patients without RBD, patients with WD and RBD reported significantly higher nightmare frequencies and more dreams with violent or aggressive content retrospectively; their prospectively collected dream reports contained significantly more negative emotions and aggression. Conclusions. The reduction in dream length might reflect specific cognitive deficits in WD. The lack of differences regarding dream content might be explained by the established successful WD treatment. RBD in WD had a strong impact on dreaming. In accordance with the current definition of RBD, violent, aggressive dream content seems to be a characteristic of RBD also in WD.

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

OBJECTIVE: Quantitative data are reported on rapid eye movement (REM) sleep behavior disorder (RBD) in a cohort of predominantly neurological Wilson's disease (WD). METHODS: A total of 41 patients with WD and 41 healthy, age- and gender-matched controls were studied by conducting face-to-face interviews, neurological and clinical examinations, laboratory tests, and WD- and RBD-specific scales. Video-polysomnography and quantification of REM sleep without atonia (RWA) were conducted in 35 patients and 41 controls. RESULTS: Patients with WD showed significantly worse sleep quality, less sleep efficiency, increased wakefulness after sleep onset, and more arousals compared to healthy controls. Five patients with WD (four women) fulfilled the diagnostic criteria for RBD with significantly higher values in RWA, RBD Questionnaire-Hong Kong, and RBD Screening Questionnaire compared to patients with WD without RBD. In three patients with WD, RBD had manifested before any other symptom that could be attributed to WD. Percentage of RWA was significantly lower in WD without RBD than in WD with RBD, but still significantly increased compared to controls. CONCLUSIONS: RBD can be comorbid with WD. RWA is commonly present in WD, both in the presence or absence of clinical RBD. A causal connection is possible, though retrospective determination of RBD onset and the low number of patients do not allow a definitive conclusion at this point. However, screening for WD in idiopathic RBD is available at low cost and is recommended. Early-stage copper chelation therapy provides a highly effective treatment to prevent further WD manifestations and might also control the comorbid RBD.

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

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 α-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.

Dreaming under antidepressants: a systematic review on evidence in depressive patients and healthy volunteers.

Sleep related symptoms of depression include sleep fragmentation, early morning awakening, decreased rapid eye movement (REM) sleep latency, increased REM density, and more negative dream content. Most tricyclic antidepressants (ADs) increase total sleep time and decrease wake time after sleep onset, while many selective serotonin reuptake inhibitors (SSRIs) have an opposite effect. However, almost all ADs prolong REM sleep latency and reduce the amount of REM sleep. Case reports and research data indicate a strong effect of ADs on dream recall and dream content. We performed a systematic review (1950 to August 2010) about ADs impact on dreaming in depressive patients and healthy volunteers. Twenty-one clinical studies and 25 case reports were eligible for review and document a clear AD effect on dreaming. The major finding, both in depressed patients and in healthy volunteers, is a decrease of dream recall frequency (DRF) under ADs. This is a rather consistent effect in tricyclic ADs and phenelzine, less consistently documented also for SSRIs/serotonin norepinephrine reuptake inhibitors (SNRIs). Tricyclic ADs induce more positive dream emotions. Withdrawal from tricyclic ADs and from the monoamine oxidase inhibitors phenelzine and tranylcypromine may cause nightmares. Intake and even more withdrawal of SSRIs/SNRIs seem to intensify dreaming, which may be experienced in different ways; a potential to cause nightmares has to be taken into account. Though there are clear-cut pharmacological effects of ADs on DRF and dream content, publications have been surprisingly scarce during the past 60 years. There is evidence of a gap in neuropsychopharmacological research. AD effects on dreams should be recognized and may be used in treatment.

Wilson?s disease presenting as rapid eye movement sleep behavior disorder: a possible window to early treatment / Doença de Wilson apresentando-se com transtorno comportamental do sono REM: uma janela possível para instituição de tratamento precoce

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 α-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. .

Objetivo 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. .

Urinary 6-hydroxy-melatonin-sulfate excretion and circadian rhythm in patients with restless legs syndrome.

The precise etiology of the restless legs syndrome (RLS) is unknown. Sensory and motor symptoms of RLS worsen during evening/night, coincident with the physiological peak of pineal melatonin excretion. Decreased melatonin levels have been reported in insomnia, which is an associated feature of RLS. Melatonin substitution improved insomnia. A potential association between the idiopathic RLS (iRLS) and alterations in melatonin excretion was therefore explored. Daytime (7:00-22:00 hr) and night-time (22:00-7:00 hr) urinary excretion of 6-OH-melatonin-sulfate (aMLTs) was measured in 15 patients with iRLS and 11 controls by a radioimmunoassay. There was no significant difference between daytime and night-time urinary aMLTs excretion in iRLS as compared with controls (daytime: 6.14 +/- 5.20 ng versus 5.02 +/- 5.11 ng, NS; night-time: 21.07 +/- 17.05 ng versus 22.92 +/- 16.52 ng, NS). Our data do not provide evidence for a decrease of cumulative melatonin production in iRLS. Insomnia in RLS does not seem to be correlated with a deficit of melatonin.