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Claudia Trenkwalder

Publications and source records attributed to Claudia Trenkwalder.

15 recordsLinked to original sources
PubMed2025

Post-traumatic stress disorder and REM-sleep behavior disorder: exploring genetic associations and causal links.

OBJECTIVE: To explore potential genetic and/or causal associations between Post-Traumatic Stress Disorder and neurodegeneration-related isolated/idiopathic rapid-eye-movement sleep behavior disorder. METHODS: We conducted polygenic risk score, genetic correlation, and Mendelian randomization analyses using the latest genome-wide association studies summary statistics and individual genotyping data. Next, a blinded observer examined dopamine transporter imaging binding status-a marker of neurodegeneration-in patients with isolated/idiopathic rapid-eye movement sleep behavior disorder, with (N = 6) and without Post-Traumatic Stress Disorder (N = 32). RESULTS: Polygenic risk scores for Post-Traumatic Stress Disorder were associated with isolated/idiopathic rapid-eye-movement sleep behavior disorder, with each standard deviation increase linked to 14.7% higher odds (odds ratio = 1.15, 95% confidence interval: 1.04 to 1.26, p = 0.005). However, genetic correlation was weak, and Mendelian randomization did not support a potential causal relationship. The proportion of individuals with abnormal dopamine transporter imaging binding status was significantly higher in the Post-Traumatic Stress Disorder group compared to those without the disorder (p=0.01, X2 = 6.62). INTERPRETATION: Polygenic risk scores analysis identified an association between Post-Traumatic Stress Disorder and neurodegeneration-related isolated/idiopathic rapid-eye-movement sleep behavior disorder, consistent with the result from the small exploratory substudy. The lack of strong genetic correlation or causation may reflect limited sample size. Further research with larger and more diverse cohorts is crucial to clarify the genetic, biological and physiological mechanisms underlying this association.

Journal Article↗
PubMed2003

Increased muscle activity during rapid eye movement sleep correlates with decrease of striatal presynaptic dopamine transporters. IPT and IBZM SPECT imaging in subclinical and clinically manifest idiopathic REM sleep behavior disorder, Parkinson's disease, and controls.

STUDY OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by complex behavior during REM sleep. The etiology of this disorder is still unknown, but a recent study showed that RBD precedes symptoms of Parkinson disease (PD) by several years, and in a previous study, we found reduced striatal dopamine transporters in idiopathic clinically manifest RBD. DESIGN: Hypothesizing that subclinical RBD shows a less severe reduction of striatal dopamine transporters than clinically manifest RBD, we studied striatal postsynaptic dopamine D2-receptors with (S)-2hydroxy-3iodo-6-methoxy-([1-ethyl-2-pyrrolidinyl]methyl) benzamide labeled with iodine 123 (IBZM) and the striatal presynaptic dopamine transporters with (N)-(3-iodopropene-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane labeled with iodine 123 (IPT) using single-photon emission computed tomography (SPECT) in the following groups: 8 patients with idiopathic subclinical RBD, 8 patients with idiopathic clinically manifest RBD, 11 controls, and 8 patients with PD stage Hoehn & Yahr I. RESULTS: The IPT uptake was highest in controls. There was a significant decrease in IPT uptake from controls to patients with subclinical RBD, from patients with subclinical RBD to clinically manifest RBD, and from patients with clinically manifest RBD to patients with PD (controls: right = 4.07 +/- 0.29, left = 4.07 +/- 0.30; subclinical RBD: right = 3.56 +/- 0.21, left = 3.55 +/- 0.25; clinically manifest RBD: right = 3.18 +/- 0.43, left = 3.2 +/- 0.43; PD: ipsilateral to the clinically affected body side = 3.25 +/- 0.35, contralateral to the clinically affected body side = 2.51 +/- 0.28). Muscle activity during REM sleep lasting persistently longer than 0.5 seconds was independently associated with reduction of striatal dopamine transporters (P = 0.001). The IBZM uptake was not significantly different between the groups. CONCLUSIONS: This study suggests that there is a continuum of reduced striatal dopamine transporters involved in the pathophysiologic mechanisms causing increased muscle activity during REM sleep in patients with subclinical RBD.

Adult↗
PubMed2003

The effect of cabergoline on sleep, periodic leg movements in sleep, and early morning motor function in patients with Parkinson's disease.

To investigate the effect of the dopamine D2 and D1 receptor agonist cabergoline on sleep, periodic leg movements (PLMs) in sleep, and early morning motor performance in patients with Parkinson's disease (PD). It was hypothesized that cabergoline had long-lasting beneficial effects on sleep and PLMs in sleep in patients with PD, after a single evening intake. A total of 15 patients with idiopathic PD underwent two nights of polysomnography and motor tests (UPDRS, tapping test) before and after 6-8 weeks of treatment with cabergoline (dosage: 3-6 mg/day). Additionally, patients completed a subjective sleep visual analog scale (VAS) before and during cabergoline treatment. Compared to baseline values, treatment with cabergoline did not change sleep efficiency or the amount of stage 1 and stage 2 sleep. The number of awakenings (22.4+/-10.1 vs 32.5+/-13.3, p<0.05) and stage shifts (119+/-42 vs 148+/-46, p<0.05) were increased during treatment with cabergoline, and PLMs in sleep were reduced (PLM index 34.9+/-44.9 vs 6.7+/-4.2 per hour, p<0.05). Cabergoline significantly improved early morning motor function, and in spite of increased phase shifts and awakenings, patients felt significantly more refreshed in the morning during cabergoline therapy. Cabergoline slightly fragmented sleep, without altering its total amount. The functional significance of this finding is uncertain. The subjective quality of sleep improved, and periodic limb movements in sleep decreased.

Activities of Daily Living↗
PubMed2002

T2*-weighted MRI differentiates multiple system atrophy from Parkinson's disease.

To compare the ability of T2*-weighted gradient echo (GE) and T2-weighted fast spin echo images to distinguish between patients with idiopathic PD and multiple system atrophy (MSA), the authors studied 15 patients with probable MSA, 40 patients with PD, and 17 healthy control subjects. Hypointense putaminal signal changes were more often observed in MSA than in PD using T2* but not T2-weighted images, indicating that T2*-weighted GE sequences are of diagnostic value for patients with parkinsonism.

Aged↗
PubMed2002

Assessment of spontaneously occurring periodic limb movements in sleep in the rat.

OBJECTIVE: Periodic limb movements in sleep (PLMS) are often associated with the restless legs syndrome (RLS). Although the dopaminergic system seems to be involved, the pathophysiology of PLMS and RLS is still obscure. The objective of this study is to explore whether a PLMS-like phenomenon can be observed in rodents in order to elucidate the underlying mechanisms. METHODS: In a group of young and old rats (1.4-1.6 and 16.2-20.5 months, respectively), sleep-wake behavior was recorded and hindlimb movements were detected by means of a magneto-inductive device during two 12-h light periods. Furthermore, in the old rats, recordings were made after administration of the dopamine antagonist haloperidol (HAL) on three consecutive days. Periodic hindlimb movements (PHLM) during nonrapid eye movement sleep (NREM) were identified according to modified human criteria. RESULTS: In the young animals, no PHLM were observed, whereas, 4 out of 10 old rats showed PHLM, two of them have more than 5 PHLM/h. Haloperidol affects neither the sleep pattern nor the number of PHLM. Interestingly, the percentage of old rats spontaneously displaying PHLM resembles the prevalence of PLMS in the elderly. CONCLUSIONS: Our study demonstrates for the first time that periodic hindlimb movements (PHLM) in sleep can occur spontaneously in rats. A clear effect of age on this phenomenon was seen, with only old animals displaying PHLM. To validate whether the observed PHLM constitute a good model for human PLMS or even RLS, their pharmacological properties need to be characterized in a large number of PHLM positive animals.

Aging↗
PubMed2002

Activity of the hypothalamic-pituitary-adrenal axis in multiple sclerosis: correlations with gadolinium-enhancing lesions and ventricular volume.

The known interaction between the immune system and the hypothalamic-pituitary-adrenal axis led us to explore the interrelation between magnetic resonance imaging findings and the hypothalamic-pituitary-adrenal axis activity in 53 multiple sclerosis patients. The cortisol release induced by the dexamethasone-corticotropin-releasing hormone test was negatively associated with the presence and number of gadolinium-enhancing lesions and positively associated with ventricular size. This finding suggests a protective effect of the hypothalamic- pituitary-adrenal drive on acute lesional inflammation in multiple sclerosis, probably by limiting immune overshoot. In contrast, the nature of the correlation between hypothalamic-pituitary-adrenal hyperdrive and brain atrophy remains to be determined.

Adult↗
PubMed2002

Complex segregation analysis of restless legs syndrome provides evidence for an autosomal dominant mode of inheritance in early age at onset families.

A strong familial component of restless legs syndrome (RLS) is known. The objective of this study therefore was to investigate the likely mode of inheritance of RLS. RLS patients and their first-degree relatives were investigated and classified in RLS affected and RLS nonaffected subjects. Assessments were based on direct, personal standardized diagnostic interviews. Complex segregation analysis was performed with the families stratified according to the mean age at onset of the disease within the families. Two hundred thirty-eight RLS patients, 537 first-degree relatives, and 133 spouses were interviewed. Two groups of families were stratified: mean age at onset up to 30 years of age (Group A) and older than 30 years (Group B; p < 0.005). In Group A, segregation analysis strongly favored a single major gene acting autosomal dominant with a multifactorial component. Parameter estimates were 0.003 for the allele frequency, 1.0 for the penetrance, and 0.005 for the phenocopy rate. In Group B, no evidence for a major gene could be elucidated. The segregation pattern found in our families argues for an autosomal allele acting dominantly in RLS families with an early age at onset of symptoms and suggests that RLS is a causative heterogeneous disease.

Adolescent↗
PubMed2002

Long-term course of restless legs syndrome in dialysis patients after kidney transplantation.

Restless legs syndrome (RLS) is a common cause of sleep disturbance and is frequently experienced by hemodialysis patients. Factors triggering the disease in uremia have not yet been identified. To our knowledge, the course of RLS symptoms after kidney transplantation has not been investigated systematically. We investigated the clinical long-term course of RLS in hemodialysis patients who underwent kidney transplantation. Patients were given a standardized questionnaire three times: at baseline, and twice after their kidney transplants. The severity of RLS was rated by the patients (0 =no symptoms, 10 = very severe symptoms). The description of the final outcome was based on the last follow-up visit. Eleven of 64 hemodialysis patients with RLS received a transplant (5 men, 6 women; severity of RLS at baseline, 7.8 +/- 0.7 [mean +/- SEM]). In all patients, RLS symptoms disappeared within 1 to 21 days after transplantation. At follow-up visits, 4 patients whose transplanted kidneys still functioned well were still free of RLS symptoms up to the longest follow-up period of 9 years. In 3 other patients, RLS symptoms gradually reappeared (severity, 1 +/- 0). In 3 of 11 patients, the transplant failed and RLS symptoms reoccurred within 10 days to 2 months (severity, 7.3 +/- 2.6). RLS symptoms reoccurred in 1 patient with failure of the transplant but disappeared again after a second, successful transplant. Kidney transplantation has a strong and positive influence on RLS symptoms in hemodialysis patients. Hemodialysis patients can expect a substantial improvement of RLS symptoms after a successful kidney transplant.

Adult↗
PubMed2002

Microstructure of the non-rapid eye movement sleep electroencephalogram in patients with newly diagnosed Parkinson's disease: effects of dopaminergic treatment.

We investigated non-rapid eye movement (non-REM) sleep in patients with newly diagnosed Parkinson's disease (PD) who had never previously received dopaminergic medication. There were no significant differences in the conventional sleep parameters between de novo patients with PD and a healthy control group, but the length of stage 1 sleep and the number of awakenings increased significantly upon administration of dopaminergic drugs. Analyzing the quantitative electroencephalogram (EEG), we observed a significant reduction in the low-delta frequency range and a nonsignificant increase in the sigma frequency range in de novo patients with PD. The dopaminergic medication also nonsignificantly reduced the low-delta and sigma frequencies, the latter to the level of the controls. Possible mechanisms that may account for the observed differences are discussed. It is suggested that Parkinson's disease as well as the application of dopaminergic drugs exerts a desynchronizing effect on the sleep EEG that is reflected in a disruption of sleep continuity.

Aged↗
PubMed2002

Endocrine rhythms in patients with restless legs syndrome.

There is increased evidence that the dopaminergic system plays a major role in the pathophysiology of the restless legs syndrome (RLS). Dopamine is the major inhibitory factor of prolactin release and also influences growth hormone (hGH) secretion. The aim of this study was to measure the endocrine activity of RLS patients, to compare it with that of normal subjects and to detect possibly altered patterns of hormonal secretion in RLS patients. Prolactin, hGH and cortisol plasma levels were measured every 20 min for 24 hours in 10 male never-medicated RLS patients (aged 56 +/- 6 years) who have had mild to moderate symptoms for 15 +/- 10 years and in 8 age-matched male controls (aged 57 +/- 5 years). The blood samples taken during the night were paralleled by polysomnographic recordings including the assessment of periodic leg movements (PLM). Plasma levels as well as frequency and amplitude of the pulses of prolactin, hGH and cortisol were not different between RLS patients and controls. Both groups showed the same rhythms during the night- and daytime for all hormones. Cross correlations resulted in high correlation coefficients for each hormone at lag 0 (0.964,0.943 and 0.971 for mean locations of cortisol, hGH and prolactin, respectively). Concerning sleep parameters, there were no significant differences between the two groups apart from a higher PLMS arousal index in RLS patients (25.9 +/- 17.1) compared with the controls (12.0 +/- 9.2; p < 0.05). It is suggested that a possible dysfunction of the dopaminergic system in RLS does not affect the release of prolactin and hGH from the pituitary gland.

Chronobiology Disorders↗
PubMed2002

Iron metabolism and the risk of restless legs syndrome in an elderly general population--the MEMO-Study.

BACKGROUND: Low iron and ferritin blood levels have been observed in patients with Restless Legs Syndrome (RLS) with an inverse relation between symptom severity and ferritin level. All reports are based on single cases or case series of hospitalized patients or those from outpatient clinics. No data from population studies are available. METHODS: Cross-sectional study examining the associations between 5 measures of iron metabolism and RLS in an elderly general population in southern Germany. All 365 participants, aged 65 to 83 years, were examined neurologically and interviewed using standardized questions addressing the four minimal criteria for RLS. Iron, ferritin, transferrin, soluble transferrin receptor and C-Reactive Protein were analysed with standard laboratory methods. RESULTS: The prevalence of Restless Legs Syndrome in this population was 9.8 %. Odds Ratios associated with Restless Legs were significantly increased in the fourth quintile of iron (OR 3.08 95 % CI 1.02-9.29) and transferrin saturation (OR 5.68 95 % CI 1.18-27.26) compared with the third (middle) quintile. Increases in the first (lowest) quintile of both measures were not or borderline significant. No associations with ferritin and soluble transferrin receptor were found. CONCLUSIONS: No evidence was found that iron or ferritin deficiency are a major cause of RLS in this population study. The results support the hypothesis that changes in the complex regulation of iron metabolism contribute to the occurence of RLS.

Aged↗
PubMed2002

Clinical symptomatology and treatment of restless legs syndrome and periodic limb movement disorder.

Patients with restless legs syndrome (RLS) suffer from sensory and motor symptoms evoked in the limbs at rest. Symptoms increase in the evening and during the night. The circadian rhythm and the presence of involuntary periodic limb movement in sleep (PLMS) which are frequently associated with arousals probably cause the leading symptom of sleep disturbances in RLS. Patients who do not have typical RLS symptoms but whose polysomnography shows PLMS that either impact on sleep continuity or daytime functioning are diagnosed as having the periodic limb movement disorder (PLMD). Dopaminergic agents such as levodopa/dopa decarboxylase inhibitor (DDI) and dopamine agonists are considered the treatment of choice for RLS and PLMS. This article gives an overview of the epidemiology, pathophysiology, clinical symptomatology and diagnosis of RLS and PLMD and focuses on treatment strategies in both disorders.

Corpus Striatum↗