Urinary bladder detrusor dysfunction symptoms in lyme disease.

PURPOSE: Symptoms of urinary bladder detrusor dysfunction have been rarely reported in Lyme disease. The aim was to carry out the first systematic study to compare the prevalence of such symptoms in a group of Lyme disease patients and a group of matched controls. METHODS: A questionnaire relating to detrusor function was administered to 17 serologically positive Lyme disease patients and to 18 control subjects. RESULTS: The two groups were matched in respect of age, sex, body mass, and mean arterial blood pressure. None of the 35 subjects was taking medication which might affect urinary function and none had undergone a previous operative procedure on the lower urinary tract. Six of the Lyme patients (35%) and none of the controls (0%) had symptoms of detrusor dysfunction (P<0.01). CONCLUSIONS: This first systematic controlled study confirms that Lyme disease is associated with urinary bladder detrusor dysfunction. Further evaluation of detrusor function is warranted in this disease

Prevalence and onset of comorbidities in the CDKL5 disorder differ from Rett syndrome

Background: Initially described as an early onset seizure variant of Rett syndrome, the CDKL5 disorder is now considered as an independent entity. However, little is currently known about the full spectrum of comorbidities that affect these patients and available literature is limited to small case series. This study aimed to use a large international sample to examine the prevalence in this disorder of comorbidities of epilepsy, gastrointestinal problems including feeding difficulties, sleep and respiratory problems and scoliosis and their relationships with age and genotype. Prevalence and onset were also compared with those occurring in Rett syndrome. Methods: Data for the CDKL5 disorder and Rett syndrome were sourced from the International CDKL5 Disorder Database (ICDD), InterRett and the Australian Rett syndrome Database (ARSD). Logistic regression (multivariate and univariate) was used to analyse the relationships between age group, mutation type and the prevalence of various comorbidities. Binary longitudinal data from the ARSD and the equivalent cross-sectional data from ICDD were examined using generalized linear models with generalized estimating equations. The Kaplan-Meier method was used to estimate the failure function for the two disorders and the log-rank test was used to compare the two functions. Results: The likelihood of experiencing epilepsy, GI problems, respiratory problems, and scoliosis in the CDKL5 disorder increased with age and males were more vulnerable to respiratory and sleep problems than females. We did not identify any statistically significant relationships between mutation group and prevalence of comorbidities. Epilepsy, GI problems and sleep abnormalities were more common in the CDKL5 disorder than in Rett syndrome whilst scoliosis and respiratory problems were less prevalent. Conclusion: This study captured a much clearer picture of the CDKL5 disorder than previously possible using the largest sample available to date. There were differences in the presentation of clinical features occurring in the CDKL5 disorder and in Rett syndrome, reinforcing the concept that CDKL5 is an independent disorder with its own distinctive characteristics

Physiological and psychological individual differences influence resting brain function measured by ASL perfusion

Effects of physiological and/or psychological inter-individual differences on the resting brain state have not been fully established. The present study investigated the effects of individual differences in basal autonomic tone and positive and negative personality dimensions on resting brain activity. Whole-brain resting cerebral perfusion images were acquired from 32 healthy subjects (16 males) using arterial spin labeling perfusion MRI. Neuroticism and extraversion were assessed with the Eysenck Personality Questionnaire-Revised. Resting autonomic activity was assessed using a validated measure of baseline cardiac vagal tone (CVT) in each individual. Potential associations between the perfusion data and individual CVT (27 subjects) and personality score (28 subjects) were tested at the level of voxel clusters by fitting a multiple regression model at each intracerebral voxel. Greater baseline perfusion in the dorsal anterior cingulate cortex (ACC) and cerebellum was associated with lower CVT. At a corrected significance threshold of p < 0.01, strong positive correlations were observed between extraversion and resting brain perfusion in the right caudate, brain stem, and cingulate gyrus. Significant negative correlations between neuroticism and regional cerebral perfusion were identified in the left amygdala, bilateral insula, ACC, and orbitofrontal cortex. These results suggest that individual autonomic tone and psychological variability influence resting brain activity in brain regions, previously shown to be associated with autonomic arousal (dorsal ACC) and personality traits (amygdala, caudate, etc.) during active task processing. The resting brain state may therefore need to be taken into account when interpreting the neurobiology of individual differences in structural and functional brain activity

Clinical and biological progress over 50 years in Rett syndrome

In the 50 years since Andreas Rett first described the syndrome that came to bear his name, and is now known to be caused by a mutation in the methyl-CpG-binding protein 2 (MECP2) gene, a compelling blend of astute clinical observations and clinical and laboratory research has substantially enhanced our understanding of this rare disorder. Here, we document the contributions of the early pioneers in Rett syndrome (RTT) research, and describe the evolution of knowledge in terms of diagnostic criteria, clinical variation, and the interplay with other Rett-related disorders. We provide a synthesis of what is known about the neurobiology of MeCP2, considering the lessons learned from both cell and animal models, and how they might inform future clinical trials. With a focus on the core criteria, we examine the relationships between genotype and clinical severity. We review current knowledge about the many comorbidities that occur in RTT, and how genotype may modify their presentation. We also acknowledge the important drivers that are accelerating this research programme, including the roles of research infrastructure, international collaboration and advocacy groups. Finally, we highlight the major milestones since 1966, and what they mean for the day-to-day lives of individuals with RTT and their families

Cardiovascular regulation in the period preceding vasovagal syncope in conscious humans

To study cardiovascular control in the period leading to vasovagal syncope we monitored beat-to-beat blood pressure, heart rate (HR) and forearm blood flow in 14 patients with posturally related syncope, from supine through to tilt-induced pre-syncope. Signals of arterial blood pressure (BP) from a Finapres photoplethysmograph and an electrocardiograph (ECG) were fed into a NeuroScope system for continuous analysis. Non-invasive indices of cardiac vagal tone (CVT) and cardiac sensitivity to baroreflex (CSB) were derived on a beat-to-beat basis from these data. Brachial vascular resistance (VR) was assessed intermittently from brachial blood flow velocity (Doppler ultrasound) divided by mean arterial pressure (MAP). Patients underwent a progressive orthostatic stress test, which continued to pre-syncope and consisted of 20 min head-up tilt (HUT) at 60 deg, 10 min combined HUT and lower body suction (LBNP) at -20 mmHg followed by LBNP at -40 mmHg. Pre-syncope was defined as a fall in BP to below 80 mmHg systolic accompanied by symptoms. Baseline supine values were: MAP (means ± S.E.M.) 84.9 ± 3.2 mmHg; HR, 63.9 ± 3.2 beats min-1; CVT, 10.8 ± 2.6 (arbitrary units) and CSB, 8.2 ± 1.6 ms mmHg-1. HUT alone provoked pre-syncope in 30 % of the patients whilst the remaining 70 % required LBNP. The cardiovascular responses leading to pre-syncope can be described in four phases. Phase 1, full compensation: where VR increased by 70.9 ± 0.9 %, MAP was 89.2 ± 3.8 mmHg and HR was 74.8 ± 3.2 beats min-1 but CVT decreased to 3.5 ± 0.5 units and CSB to 2.7 ± 0.4 ms mmHg-1. Phase 2, tachycardia: a progressive increase in heart rate peaking at 104.2 ± 5.1 beats min-1. Phase 3, instability: characterised by oscillations in BP and also often in HR; CVT and CSB also decreased to their lowest levels. Phase 4, pre-syncope: characterised by sudden decreases in arterial blood pressure and heart rate associated with intensification of the symptoms of pre-syncope. This study has given a clearer picture of the cardiovascular events leading up to pre-syncope. However, the mechanisms behind what causes a fully compensated system suddenly to become unstable remain unknown

Dysautonomia Causing Severe Orthostatic Hypotension: An Important, Early Finding in Neurodegenerative Disorders.

Orthostatic hypotension is common and dangerous; it has neurogenic and nonneurogenic causes. We present the case of a 40-year-old man with severe neurogenic hypotension, caused by young-onset multiple system atrophy. In patients presenting with neurogenic orthostatic hypotension, underlying neurodegenerative diseases should always be considered. (Level of Difficulty: Advanced.)