Rasagiline improves polysomnographic sleep parameters in patients with Parkinson's disease: a double-blind, baseline-controlled trial.

BACKGROUND AND PURPOSE: The aim was to study the effects of rasagiline on sleep quality in patients with Parkinson's disease (PD) with sleep disturbances. Sleep disorders are common in PD. Rasagiline is widely used in patients with PD, but double-blind polysomnographic trials on its effects on sleep disturbances are missing. METHODS: This was a single-center, double-blind, baseline-controlled investigator-initiated clinical trial of rasagiline (1 mg/day) over 8 weeks in patients with PD with sleep disturbances. Blinding was achieved by running a strategic matched placebo parallel group. Co-primary outcome measures were the changes between baseline and end of the treatment period in sleep maintenance/efficiency as assessed by polysomnography and the Parkinson's Disease Sleep Scale Version 2 (PDSS-2) score. RESULTS: A total of 20 of 30 patients were randomized to rasagiline (mean ± SD age, 69.9 ± 6.9 years; 10 male; Hoehn-Yahr stage, 1.9 ± 0.8). Compared with baseline, sleep maintenance was significantly increased at the end of the treatment period (relative change normalized to baseline, +16.3 ± 27.9%; P = 0.024, paired two-sided t-test) and a positive trend for sleep efficiency was detected (+12.1 ± 28.6%; P = 0.097). Treatment with rasagiline led to significantly decreased wake time after sleep onset, number of arousals, percentage of light sleep and improved daytime sleepiness as measured by the Epworth Sleepiness Scale. We did not observe changes in the co-primary endpoint PDSS-2 score, and no correlations of polysomnographic sleep parameters or PDSS-2 score with motor function (Unified Parkinson's Disease Rating Scale motor score). Rasagiline was well tolerated with no unexpected adverse events. CONCLUSIONS: In patients with PD with sleep disturbances, rasagiline showed beneficial effects on sleep quality as measured by polysomnography. These effects were probably not related to motor improvement or translated into improved overall sleep quality perception by patients.

Novel frameshift mutation in the CACNA1A gene causing a mixed phenotype of episodic ataxia and familiar hemiplegic migraine.

Episodic ataxia type 2 (EA2, MIM#108500) is the most common form of EA and an autosomal-dominant inherited disorder characterized by paroxysmal episodes of ataxia. The disease causative gene CACNA1A encodes for the alpha 1A subunit of the voltage-gated P/Q-type calcium channel. We report on a family with a novel mutation in the CACNA1A gene. The clinical symptoms within the family varied from the typical clinical presentation of EA2 with dysarthria, gait ataxia and oculomotor symptoms to migraine and dystonia. A novel nonsense mutation of the CACNA1A gene was identified in all affected family members and is most likely the disease causing molecular defect. The pharmacological treatment with acetazolamide (AAA) was successful in three family members so far. Treatment with AAA led to a reduction of migraine attacks and an improvement of the dystonia. This relationship confirmed the hypothesis that this novel mutation results in a heterogeneous phenotype and confutes the coincidence with common migraine. Dystonia is potentially included as a further part of the phenotype spectrum of CACNA1A gene mutations.

Production of a monoclonal antibody by in vitro immunization that recognizes a native chondroitin sulfate epitope in the embryonic chick limb and heart.

We report the production of a monoclonal antibody (d1C4) by in vitro immunization that has immunoreactivity with a native chondroitin sulfate epitope in embryonic chick limb and heart. Murine lymphocytes were stimulated by direct exposure to unfixed, unsolubilized precartilage mesenchymal aggregates in high-density micromass culture derived from Stage 22-23 chick limb buds. Specificity of d1C4 reactivity was demonstrated by sensitivity of immunohistochemical staining to pretreatment with chondroitinase ABC or AC, preferential immunoreactivity with chondroitin-6-sulfate glycosaminoglycan (CS-C GAG) in ELISA, and competition of immunohistochemical staining with CS-C GAG. Immunohistochemical analysis of the expression of the d1C4 epitope revealed a striking localization of immunoreactivity in the extracellular matrix (ECM) of precartilage aggregates of chick limb mesenchyme in high-density micromass culture by 16 hr and the prechondrogenic limb core at Stage 23 in vivo. Immunoreactivity in both cultured limb mesenchyme and the embryonic limb continued through differentiation of prechondrogenic condensations into cartilage tissue. In the developing chick heart, d1C4 staining was found throughout the ECM of atrioventricular cushion tissue by Stage 25, but was localized to mesenchyme adjacent to the myocardium in the outflow tract cushions. There was an abrupt demarcation between d1C4-reactive intracardiac mesenchyme and unreactive extracardiac mesenchyme of the dorsal mesocardium in the Stage 22 embryo. This study demonstrates the efficacy of in vitro immunization of lymphocytes for the production of MAbs to native ECM constituents, such as CS-GAGs. Immunohistochemical data utilizing d1C4 suggest that CS-GAGs bearing this epitope may be important in early morphogenetic events leading to cartilage differentiation in the limb and valvuloseptal morphogenesis in the heart.

Correlation of pediatric echocardiographic Doppler and catheter-derived valvar aortic stenosis gradients and the influence of aortic regurgitation.

This report suggests that in the absence of aortic regurgitation, Doppler peak and mean gradients are useful predictors of catheter peak-to-peak aortic stenosis gradients >50 mm Hg; however, in the presence of aortic regurgitation, the predictive value diminishes dramatically, but improves when electrographic data are incorporated. We present potentially useful equations to help predict the need for interventional catheterization for valvar aortic stenosis.

Comparison of intraoperative transesophageal echocardiography to epicardial imaging in children undergoing ventricular septal defect repair.

Intraoperative transesophageal echocardiography was compared with epicardial echocardiography after ventricular septal defect repair. This comparison was made in 18 children aged 7 to 137 months (median, 32 months), weighing 6.3 to 49.1 kg (median, 10.8 kg) from November 1989 to January 1991. Ventricular septal defect types were perimembranous (six), malalignment (seven), supracristal (three), midmuscular (one), and inlet (one). Eight children had isolated ventricular septal defects, four had tetralogy of Fallot, three had double outlet right ventricle, two had double chambered right ventricle, and one had pulmonary stenosis. Patch interrogation was complete in 17 of 18 transesophageal echocardiography and 16 of 18 epicardial echocardiography studies. Inability to fully interrogate the ventricular septal defect patch by epicardial echocardiography occurred in two children as a result of anterior ventricular septal defect location, limited epicardial exposure, and surgical hardware interference. Incomplete transesophageal echocardiography patch interrogation occurred in the child with the midmuscular ventricular septal defect. Seven residual ventricular septal defects were documented by color flow Doppler in six patients. Five of seven residual defects were demonstrated by both real-time transesophageal echocardiography and epicardial echocardiography imaging. Transesophageal echocardiography and epicardial echocardiography missed 1 and 7 defects, respectively. The missed defects were different with each technique and were confirmed by postoperative surface echocardiography. No residual defects of sufficient size to require reoperation were found as determined by combination color flow jet analysis and intraoperative oximetry (no pulmonary to systemic flow ratio was greater than 1.50). Patches caused two-dimensional and Doppler signal masking, but this was not limiting because all residual defects were found at the margins of the ventricular septal defect patch.(ABSTRACT TRUNCATED AT 250 WORDS)

Image-based display of activation patterns derived from scattered electrodes.

Presentation of electrophysiologic data, such as activation patterns, can take many forms, the most common of which are hand- or machine-drawn isochronal maps. We present an image-based method which provides accurate matching between electrophysiologic data and the anatomic sites from which the data were derived. This method is linear, simple, and straightforward to implement, and presents results in a format which is easy to understand and interpret.

Adenosine's effectiveness in long RP' re-entrant tachycardia: additional evidence of the decremental qualities of the retrograde limb.

Adenosine's ability to terminate atrioventricular (AV) re-entrant supraventricular tachycardia is well documented. Typically, termination occurs as a consequence of transient conduction block in the atrioventricular node, a tissue with decremental qualities. However, the atrioventricular node is not always the site of action when adenosine is used on the re-entrant types of long RP' tachycardias. These tachycardias are, in part, characterized by the decremental qualities of the retrograde limb of the tachycardia circuit, which, in turn, are typically exemplified by retrograde Wenckebach during ventricular (VVI) pacing during intracardiac electrophysiology studies. This case report involves adenosine's ability to block conduction in the retrograde limb of the permanent form of junctional reciprocating tachycardia to provide further evidence as to the AV "nodelike" decremental qualities of this limb.

Circadian blood pressure rhythms in elderly hypertensive patients.

Blood pressure was recorded for 24 h in 121 essential hypertensive patients aged between 20 and 90 years. To characterize the circadian blood pressure rhythm, the differences between the daytime blood pressures (recorded at 8-min intervals between 8 a.m. and 10 p.m.) and the night-time blood pressures (recorded at 30-min intervals between 10 p.m. and 8 a.m.) were calculated. The difference between daytime and night-time blood pressures was significantly (P less than 0.01) decreased in elderly hypertensive patients aged between 65 and 90 years compared with in those aged 20-39 years. In patients with heart insufficiency the circadian blood pressure rhythmicity was significantly (P less than 0.05) further reduced compared with in uncomplicated hypertensives. This may be explained by increased sympathetic tonus in patients with heart insufficiency and reduced vascular compliance may be the cause of the overall reduced circadian blood pressure rhythmicity in elderly hypertensive patients.

Laughing as a manifestation of rapid eye movement sleep behavior disorder.

BACKGROUND: Among the range of sleep-related behavior displayed by patients with rapid eye movement (REM) sleep behavior disorder (RBD), aggressive acts are particularly common, while pleasant behaviors have rarely been reported. We aimed at identifying the frequency and characteristics of patients who displayed laughing as a pleasant, nonviolent manifestation of RBD. METHODS: We reviewed 67 consecutive polysomnographic recordings of patients with RBD, obtained in our sleep laboratory between July 2004 and July 2009. RESULTS: We identified 14 patients (21% of our RBD patients with degenerative parkinsonism: 10 males, mean age 63 ± 11 years) who repeatedly laughed during REM sleep. Ten patients had idiopathic Parkinson's disease, 3 suffered from multisystem atrophy and 1 patient was diagnosed with dementia with Lewy bodies. Other RBD-associated behaviors included smiling, crying, aggressive behavior, screaming, and somniloquia. Nine of the 14 patients were depressed during daytime. CONCLUSION: Laughing belongs to the spectrum of behavioral manifestations of RBD. Many of our patients with RBD-associated laughter were depressed, suggesting a dissociation between emotional expression during daytime and REM sleep.

Unmasking of a second atrioventricular accessory connection by adenosine in a child with a long RP' reentrant tachycardia.

A second unidirectional, retrograde accessory atrioventricular pathway was unmasked by adenosine during the intracardiac evaluation of a child with a reentrant long RP' tachycardia. This case is further evidence of the value of adenosine during the evaluation of these types of tachycardias.

Color flow Doppler in the diagnosis of double-chambered right ventricle: a demographic and echocardiographic study.

UNLABELLED: The purpose of this study was to evaluate the demographic and echocardiographic data of patients diagnosed with double-chambered right ventricle and attempt to explain a perceived rise in the incidence. DEFINITION: Double-chambered right ventricle (DCRV) is a division of the right ventricle into two chambers by a hypertrophied muscle bundle. METHODS: The medical records of patients diagnosed with DCRV were reviewed, and demographic, echocardiographic, and catheterization data were tabulated. Annual incidence of DCRV, based on year of birth, was compared to yearly detection rate, based on year of DCRV diagnosis. To evaluate the influence of color flow Doppler on the frequency of diagnosis of DCRV, demographics of patients born prior to September 1986 (when utilization of color Doppler began in our institution) were compared to those born after that date. RESULTS: Despite an unchanged annual incidence of DCRV, yearly detection rate of this lesion rose significantly following the introduction of color flow Doppler to our institution (September 1986). DCRV was diagnosed earlier and was accompanied by earlier catheterization, which also showed lower right ventricular body gradients after September 1986. Associated anomalies, both cardiac and noncardiac, in our population differed from those reported in previous series. CONCLUSION: This study infers that the advent of color flow Doppler significantly enhanced the diagnosis of DCRV in our pediatric patients and led to a perceived rise in incidence.

Late endocardial pacing lead body migration compromising Fontan physiology.

Migration of intracardiac transvenous pacing leads may occur. There is a known risk of intrapulmonary ventricular pacing lead migration in patients with endocardial lead systems. In the current report we present the late intrapulmonary migration of an endocardial atrial pacing lead body. The patient had undergone antitachycardia pacemaker placement to control recurrent atrial tachyarrhythmias following the Fontan procedure. Although the lead electrode remained in place and continued to pace, the lead body migrated, causing severe obstruction to blood flow. This resulted in severe cardiac decompensation, which was ultimately ameliorated by lead repositioning.

Early results of AV sequential pacing on left ventricular outflow obstruction after Senning procedure.

Dual chamber pacing was shown to decrease left ventricular outflow tract (LVOT) obstruction in patients with hypertrophic cardiomyopathy 30 years ago. We report early results of AV sequential pacing from the LV apex in a patient with transposition of the great arteries who is post-Senning procedure. LVOT obstruction resulted from septal deviation and systolic anterior motion of the mitral valve. Pacing was indicated for sinus node dysfunction. AV sequential pacing with a short optimal AV interval of 60 ms demonstrated a 45% reduction in the degree of LVOT obstruction. This article suggests that LVOT obstruction after the Senning procedure can be palliated by asynchronous septal contraction induced by AV sequential pacing, even if the activation is from LV apex, and avoid or postpone surgery in selected situations.

Identification of an autocrine signaling pathway that amplifies induction of endocardial cushion tissue in the avian heart.

Endocardial cushion tissue is formed by an epithelial-mesenchymal transformation of endocardial cells, a process which results from an inductive interaction between the myocardium and endocardium within the atrioventricular (AV) and outflow tract (OT) regions of the heart. We report here that a protein previously found to be required for myocardially induced transformation of endocardial cells in vitro, ES/130, is highly expressed within the AV and OT regions not only by myocardial cells, but also by the endocardium and its mesenchymal progeny. Given these findings and others, we have tested the hypothesis that endocardial cushion tissue secretes factors which autoregulate its transformation to mesenchyme. Endocardial cushion tissue was cultured and its conditioned growth medium was harvested and applied to nontransformed endocardial cells maintained in the absence of the inductive myocardium. This treatment resulted in endocardial cell invasion into three-dimensional collagen gels plus increased expression of proteins associated with endocardial cell transformation in vivo. Whereas endocardial cushion tissue was found to express ES/130 protein in vivo and in vitro, minimal detection of ES/130 in its conditioned growth medium was observed in immunoblots. Attempts to inhibit the mesenchyme-promoting activity of the conditioned medium with ES/130 antisense were unsuccessful. However, strong intracellular ES/130 expression was detected in endocardial cells, and this expression correlated with the ability of endocardial cells to transform. For example, the minority of endocardial cultures that failed to transform in response to conditioned medium treatment also failed to undergo increased expression of ES/130. These observations are interpreted to suggest that (i) endocardial cushion tissue secretes factors that promote its transformation to mesenchyme, and (ii) while endocardial cushion tissue appears to signal through secretion of factors other than or in addition to ES/130, intracellular ES/130 expression nevertheless may be a target endocardial cell response required for endocardial cell transformation.