Background: Parkinson’s disease (PD) is a neurodegenerative disorder that causes distinct motor impairments (i.e., resting tremor, bradykinesia, rigidity, postural instability) and affects approximately one percent of the global population over the age of 60 years. Currently, there is no cure and diagnosis remain challenging due to the lack of well validated biomarkers. Prodromal PD is a phase that predates the onset of motor symptoms but includes brain changes and nonmotor symptoms, such as rapid eye movement sleep behaviour disorder (RBD) and hyposmia. Diffusion tensor imaging (DTI) provides non-invasively acquired metrics of microstructural changes in white matter and subcortical tissue and has potential as a biomarker for PD. To date, most DTI studies have focused on the clinical phase of PD. Investigating potential biomarkers in the prodromal phase of the disease is key for early diagnosis and treatment. This study had two primary objectives: (1) to investigate how white matter microstructure changes in different phases of PD progression, and (2) to investigate how sleep and motor symptoms relate to white matter microstructure in different phases of PD. Methods: All study data were downloaded from the Parkinson’s Progression Markers Initiative database. Subjects included 21 heathy controls (mean age=68.17±4.69; 6 female), 20 individuals with prodromal PD (14 with RBD and 6 with hyposmia) (mean age=67.95±5.90; 6 female), and 17 individuals with clinical PD (mean age=67.69±5.97; 6 female) (at baseline and one-year later). Tract based spatial statistics were used to determine between group differences in fractional anisotropy (FA) and mean diffusivity (MD) at the whole brain level and in a region of interest (ROI), the substantia nigra. The relationship between sleep or motor symptoms and DTI metrics were investigated within each group. Results: There were no differences between the groups in age, education level, or cognitive scores. Clinical PD had significantly higher motor symptoms than healthy controls or prodromal PD, and this significantly increased from baseline to one-year later. Between group comparisons showed increased MD (reflecting increased neurodegeneration) in prodromal PD relative to clinical PD (both at baseline and one-year later), while there were no group differences between either prodromal or clinical PD and healthy controls at the whole brain level or within the ROI. Increased motor symptoms were associated with neurodegeneration (i.e., decreased FA and increased MD) for healthy controls, while increased sleep symptoms were associated with decreased MD for clinical PD. Conclusion: This was the first to study of white matter microstructure differences in a mixed prodromal PD group relative to clinical PD. The detected early brain changes may support an RBD subtype of PD with overall different pattern of neurodegeneration. However, these results are preliminary and future studies must be conducted to clarify and expand upon the microstructural differences between prodromal and clinical PD, ideally with longitudinal follow-up. / Graduate / 2019-07-27

Although sleep forms an important part of an animal’s life, there is a paucity of knowledge about sleep behaviour. The function of sleep in birds is poorly understood, even though birds spend a large part of their lives sleeping. Sleep behaviour in passerine birds has not been looked at as extensively as that of non-passerine birds. I looked at the sleep behaviour of three relatively common passerine birds occurring in southern Africa, namely the Malachite Sunbird (Nectarinia famosa), the Cape White-eye (Zosterops pallidus) and the Fan-tailed Widowbird (Euplectes axillaris). By using an infra-red sensitive camera I described basic sleep behaviours at various ambient temperatures, of all three species, such as sleep position and eye closure, and also investigated the incidence of unihemispheric sleep. Individuals of all three species spent most of the night asleep and kept on waking up intermittently throughout the night, with no significant differences between temperatures. Cape White-eyes and Malachite Sunbirds showed an increase in back sleep and a decrease in front sleep at 5oC. Little evidence of unihemispheric sleep was found, suggesting that it is more likely to occur in non-passerines, especially ground dwelling birds. Diurnal birds generally sleep during the hours of darkness. Most male southern African sunbirds have pectoral tufts, although the function of these is not always understood. In male Malachite Sunbirds it has recently been found that they display their pectoral tufts almost continuously throughout the night, whilst asleep. I explored the possible function of this behaviour and suggest that these tufts might be a deterrent to predators, as they look like ‘eyes’ in the dark. A review of the use and occurrence of pectoral tufts in southern African sunbird species is also presented. Blood glucose concentrations of most birds are much higher than those found in mammals and it is still not known how they evade the complications of such high levels. I investigated the change in blood glucose concentrations of Malachite Sunbirds at two different ambient temperatures and at different times of the night and day and explored the possibility that gluconeogenesis might be used by birds to ‘warm up’ during arousal of torpor in the early morning, before daylight. Generally blood glucose levels were fairly high, between 13.6 and 21.4 mmol/L, which was expected. Blood glucose levels were higher at 5oC than at 25oC and generally lower in the early hours of the morning. Therefore I reject the assumption that Malachite Sunbirds use gluconeogenesis as an additional form of heat generation during torpor. It is thought that the difference in the levels of blood glucose might be a function of the cold temperature and the consumption of their nectarivorous diet. This research clearly highlights the need for further studies to be undertaken in the sleeping behaviours and patterns of birds, especially in southern African species. It also shows that more studies need to be done on the use of pectoral tufts in sunbird species and furthermore it is suggested that more research is needed to elucidate the mechanism by which Malachite Sunbirds are able to rapidly ‘warm up’ during arousal, when in torpor. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2007.

The diagnosis of Parkinson’s disease (PD) follows the UK Brain Bank Criteria, which demands bradykinesia and one additional symptom, i.e. rigidity, resting tremor or postural instability. The latter is not a useful sign for the early diagnosis of PD, because it does not appear before Hoehn and Yahr stage 3. Early symptoms of PD which precede the onset of motor symptoms are hyposmia, REM sleep behavioral disorder, constipation, and depression. In addition, an increasing number of patients whose PD is related to a genetic defect are being described. Thus, genetic testing may eventually develop into a tool to identify at-risk patients. The clinical diagnosis of PD can be supported by levodopa or apomorphine tests. Imaging studies such as cranial CT or MRI are helpful to distinguish idiopathic PD from atypical or secondary PD. SPECT and PET methods are valuable to distinguish PD tremor from essential tremor if this is clinically not possible. Using all of these methods, we may soon be able to make a premotor diagnosis of PD, which will raise the question whether early treatment is possible and ethically and clinically advisable. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

The diagnosis of Parkinson’s disease (PD) follows the UK Brain Bank Criteria, which demands bradykinesia and one additional symptom, i.e. rigidity, resting tremor or postural instability. The latter is not a useful sign for the early diagnosis of PD, because it does not appear before Hoehn and Yahr stage 3. Early symptoms of PD which precede the onset of motor symptoms are hyposmia, REM sleep behavioral disorder, constipation, and depression. In addition, an increasing number of patients whose PD is related to a genetic defect are being described. Thus, genetic testing may eventually develop into a tool to identify at-risk patients. The clinical diagnosis of PD can be supported by levodopa or apomorphine tests. Imaging studies such as cranial CT or MRI are helpful to distinguish idiopathic PD from atypical or secondary PD. SPECT and PET methods are valuable to distinguish PD tremor from essential tremor if this is clinically not possible. Using all of these methods, we may soon be able to make a premotor diagnosis of PD, which will raise the question whether early treatment is possible and ethically and clinically advisable. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

No description available.

Le trouble comportemental en sommeil paradoxal (TCSP) idiopathique est caractérisé par une activité motrice indésirable et souvent violente au cours du sommeil paradoxal. Le TCSP idiopathique est considéré comme un facteur de risque de certaines maladies neurodégénératives, particulièrement la maladie de Parkinson (MP) et la démence à corps de Lewy (DCL). La dépression et les troubles anxieux sont fréquents dans la MP et la DCL. L’objectif de cette étude est d’évaluer la sévérité des symptômes dépressifs et anxieux dans le TCSP idiopathique. Cinquante-cinq patients avec un TCSP idiopathique sans démence ni maladie neurologique et 63 sujets contrôles ont complété la seconde édition du Beck Depression Inventory (BDI-II) et le Beck Anxiety Inventory (BAI). Nous avons aussi utilisé le BDI for Primary Care (BDI-PC) afin de minimiser la contribution des facteurs confondant dans les symptômes dépressifs. Les patients avec un TCSP idiopathique ont obtenu des scores plus élevés que les sujets contrôles au BDI-II (9.63 ± 6.61 vs. 4.32 ± 4.58; P < 0.001), au BDI-PC (2.20 ± 2.29 vs. 0.98 ± 1.53; P = 0.001) et au BAI (8.37 ± 7.30 vs. 3.92 ± 5.26; P < 0.001). Nous avons également trouvé une proportion plus élevée des sujets ayant des symptômes dépressifs (4/63 ou 6% vs. 12/55 ou 22%; P = 0.03) ou anxieux (9/50 or 18% vs. 21/43 ou 49%; P = 0.003) cliniquement significatifs. La proportion des sujets ayant des symptômes dépressifs cliniquement significatifs ne change pas en utilisant le BDI-PC (11/55 or 20%) Les symptômes dépressifs et anxieux sont fréquents dans le TCSP idiopathique. L’examen de routine des patients avec un TCSP idiopathique devrait inclure un dépistage systématique des symptômes dépressifs et anxieux afin de les prévenir ou les traiter. / Idiopathic rapid-eye-movement sleep behaviour (iRBD) disorder can be a premotor feature of Parkinson’s disease (PD) or dementia with Lewy bodies (DLB). Depressive and anxiety symptoms are frequent nonmotor features in PD or DLB. We assessed the frequency and severity of depressive and anxiety symptoms in patients with iRBD compared to healthy control subjects. Fifty-five iRBD patients and 63 age and sexmatched healthy subjects were studied. Participants completed the Beck Depression Inventory – Second Edition (BDI-II) and Beck Anxiety Inventory (BAI). We assessed the depressive and anxiety symptoms and compared the proportion of participants with clinically significant depressive or anxiety symptoms. We also used the BDI for Primary Care (BDI-PC) to minimize confounding factors that could overestimate depressive symptoms. iRBD patients scored higher than controls on the BDI-II (9.63 ± 6.61 vs. 4.32 ± 4.58; P < 0.001)), BDI-PC (2.20 ± 2.29 vs. 0.98 ± 1.53; P = 0.001) and BAI (8.37 ± 7.30 vs. 3.92 ± 5.26; P < 0.001). Compared to controls, we found a higher proportion of patients with iRBD with either clinically significant depressive (4/63 or 6% vs. 12/55 or 22% P = 0.03) or anxiety symptoms (9/50 or 18% vs. 21/43 or 49%; P = 0.003). The proportion of iRBD patients with clinically significant depressive symptoms remains unchanged using the BDI-PC (11/55 or 20%). Depressive and anxiety symptoms are frequent features in iRBD. Routine examination of patients with iRBD disorder should include an assessment of depressive and anxiety symptoms in order to prevent or treat them.

<p>The manifestations of early sleep disturbances on cerebrospinal fluid and their relations with early developmental competencies are understudied. Recent studies highlight cerebrospinal fluid disbursement as a potential factor associated with dysfunctions in brain development. With two studies, we explored sleep and extra-axial cerebrospinal fluid (EA-CSF) connection as a potential mechanistic pathway by which sleep dysregulation influences brain and behavior development. Specifically, we evaluated associations between (1) EA-CSF to total cerebral volume (EA-CSF/TCV) ratios, (2) parent-report of child sleep problems, and (3) social communication development in typical (Study 1) and atypical populations (Study 2). In typical infants, early sleep problems did not precede later elevated EA-CSF/TCV ratios or social-communicative competence. Elevated EA-CSF/TCV ratios were associated with impaired social communication skills, suggesting that a relationship between elevated EA-CSF/TCV ratios and social communication impairments exists regardless of neurological or sleep problems. In an atypical population with autism spectrum disorder (ASD), older children with ASD had similar EA-CSF/TCV ratios to a group of their typically developing peers. Sleep problems were negatively associated with EA-CSF/TCV ratios but positively associated with social-communicative impairments for children with ASD, highlighting the influence of sleep problems on both brain and behavioral outcomes in an atypical population. In both studies, EA-CSF volumes continue to increase during early development in the typically developing populations (but not later in the atypical sample), underlining its relevance as a marker of atypical processing. Recognizing the potential roles of EA-CSF in influencing several biosocial and behavioral aspects of development, we encourage researchers to continue to explore EA-CSF growth, especially during developmental periods of flux and transition. Future work with longitudinal data can also serve to explore sleep-related developmental changes in EA-CSF, in association with behavioral and phenotypic changes. </p>