Oral glycopyrrolate for the treatment of chronic severe drooling caused by neurological disorders in children

Excessive drooling may complicate the care of children with chronic neurological conditions by socially isolating both patients and families and by causing secondary dermatitis and infection. Normal control of saliva requires normal integrity of oral structures, normal oropharyngeal sensation, and motor functioning, as well as normal cognitive awareness and rate of salivary production. Glycopyrrolate is an anticholinergic medication with a quaternary structure that recently received Food and Drug Administration approval to treat sialorrhea due to neurological problems in children ages 3–16 years. This review summarizes the few published studies of safety and efficacy of glycopyrrolate for drooling in children with chronic neurological conditions

25-Hydroxyvitamin D Depletion Does Not Exacerbate MPTP-Induced Dopamine Neuron Damage in Mice

Recent clinical evidence supports a link between 25-hydroxyvitamin D insufficiency (serum 25-hydroxyvitamin D [25(OH)D] levels <30 ng/mL) and Parkinson’s disease. To investigate the effect of 25(OH)D depletion on neuronal susceptibility to toxic insult, we induced a state of 25(OH)D deficiency in mice and then challenged them with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We found there was no significant difference between control and 25(OH)D-deficient animals in striatal dopamine levels or dopamine transporter and tyrosine hydroxylase expression after lesioning with MPTP. Additionally, we found no difference in tyrosine hydroxylase expression in the substantia nigra pars compacta. Our data suggest that reducing 25(OH)D serum levels in mice has no effect on the vulnerability of nigral dopaminergic neurons in vivo in this model system of parkinsonism

URGE-PD: A Multi-Site, Double-Blind, Randomized, Placebo-Controlled Trial of Solifenacin succinate (VESIcare®) for the Treatment of Overactive Bladder in Parkinson’s Disease

Objective: To evaluate the safety and efficacy of solifenacin succinate (VESIcare®) in Parkinson\u27s disease patients suffering from overactive bladder (OAB). Background: Urinary dysfunction is a commonly encountered non-motor feature in many idiopathic Parkinson\u27s disease (PD) patients. While antimuscarinic drugs are often used to treat urinary symptoms, there are no controlled trials to evaluate their efficacy in PD. Methods: This was a double-blind, randomized, placebo-controlled, 3-site study that evaluated the efficacy of solifenacin succinate (VESIcare®) in idiopathic PD patients with overactive bladder (OAB) defined as at least 8 voids per 24-hr period and at least daily urinary urgency. Patients were randomized to receive solifenacin succinate 5mg or placebo for 6 weeks, and were offered the option to increase the dose to 10mg daily based upon clinical need, or continue with 5 mg daily. The primary outcome was the change in mean number of micturitions per 24 hour period as recorded on a 3-day bladder diary 12 weeks after randomization; secondary objectives included the change in the mean number of urinary incontinence episodes, the mean number of nocturia episodes, urinary urgency as measured by the The Patient Perception of Intensity of Urgency Scale (PPIUS), and the mean change in Patient Perception of Bladder Condition (PBC/PPBC). The Unified Parkinson\u27s disease Rating Scale (UPDRS) was performed at each 6-week interval visit. Results: Twenty-eight patients enrolled in the study (60% men, mean age 67.04±7.88 years (range 52-79 years)); 3 patients discontinued the study due to side effects of constipation, xerostomia and urinary rentention that resolved upon medication discontinuation. At endpoint, the mean number of urinary incontinence episodes per 24 hour period decreased significantly in the solifenacin group compared to placebo (1.48 ± 2.56 to 0.30 ± 0.31 versus 1.78 ± 1.27 to 1.61 ± 1.40, p=0.01), at a mean dose of 6mg/day. There was a trend for improvement in the motor section of the UPDRS in the solifenacin group (9.89 ± 5.58 to 8.11 ± 5.37 versus 11.75 ± 4.58 to 11.75 ± 3.98, p=0.09). Conclusions: Use of solifenancin succinate (VESIcare®) led to a significant improvement in urinary incontinence in PD patients, and was generally well tolerated. Further studies are needed to evaluate treatment of urinary dysfunction in PD

An Open Label Study of Solifenacin Succinate (VESIcare®) for the Treatment of Overactive Bladder in Parkinson’s Disease

Objective: To evaluate the safety and efficacy of solifenacin succinate (VESIcare®) in Parkinson\u27s disease patients suffering from overactive bladder (OAB) in an open-label trial. Background: Urinary dysfunction is a commonly encountered non-motor feature in many idiopathic Parkinson\u27s disease (PD) patients. There are few controlled trials that have evaluated medical management of urinary dysfunction in PD. Methods: Following a double-blind, randomized, placebo-controlled trial that evaluated the efficacy of solifenacin succinate (VESIcare®) in 28 PD patients with OAB, patients were invited to participate in a 12 week open-label study. All patients were given 5 mg of solifenacin succinate for 4 weeks; patients were allowed to remain on this dose or increase to 10 mg for an additional 4 weeks. Patients could continue to remain on this current dose, or reduce by 1 dose level until study endpoint (week 12). The primary outcome measure was the change in mean number of micturitions per 24 hour period from baseline to endpoint between active and placebo groups; secondary objectives included the change in the mean number of urinary incontinence episodes, the mean number of nocturia episodes per 24 hour period, urinary urgency as measured by the symptom severity score on The Patient Perception of Intensity of Urgency Scale (PPIUS), and the mean change in Patient Perception of Bladder Condition (PBC/PPBC). Results: Seventeen patients enrolled in the study (mean age=67.71±7.06 years), and 16 completed it (1 withdrew due to constipation). The mean number of urinary incontinence episodes per 24 hour period decreased significantly (1.33 ± 1.54 to 0.52 ± 1.01, p = 0.03), as did the number of nocturia episodes per 24 hour period (8.88 ± 3.37 to 1.64 ± 1.09, p=0.001), at a mean dose of 7.81mg/day. There was a trend noted for improvement in the PPIUS (p=0.09) as well. Other measures showed improvement, although not significantly. Other side effects included xerostomia which resolved after treatment was discontinued. Conclusions: In this open-label trial, treatment with solifenancin succinate (VESIcare®) led to a significant improvement in urinary incontinence and nocturia in PD patients, and was generally well tolerated. Further larger studies are needed to evaluate treatments for urinary dysfunction in PD patients

A functional magnetic resonance imaging study of head movements in cervical dystonia

Cervical dystonia (CD) is a neurological disorder characterized by abnormal movements and postures of the head. The brain regions responsible for these abnormal movements are not well understood, because most imaging techniques for assessing regional brain activity cannot be used when the head is moving. Recently, we mapped brain activation in healthy individuals using functional magnetic resonance imaging (fMRI) during isometric head rotation, when muscle contractions occur without actual head movements. In the current study, we used the same methods to explore the neural substrates for head movements in subjects with CD who had predominantly rotational abnormalities (torticollis). Isometric wrist extension was examined for comparison. Electromyography of neck and hand muscles ensured compliance with tasks during scanning, and any head motion was measured and corrected. Data were analyzed in three steps. First, we conducted within-group analyses to examine task-related activation patterns separately in subjects with CD and in healthy controls. Next, we directly compared task-related activation patterns between participants with CD and controls. Finally, considering that the abnormal head movements in CD occur in a consistently patterned direction for each individual, we conducted exploratory analyses that involved normalizing data according to the direction of rotational CD. The between-group comparisons failed to reveal any significant differences, but the normalization procedure in subjects with CD revealed that isometric head rotation in the direction of dystonic head rotation was associated with more activation in the ipsilateral anterior cerebellum, whereas isometric head rotation in the opposite direction was associated with more activity in sensorimotor cortex. These findings suggest that the cerebellum contributes to abnormal head rotation in CD, whereas regions in the cerebral cortex are involved in opposing the involuntary movements

Dietary Source of Vitamin D Is Associated with Parkinson Disease and Total Vitamin D Modifies the Genetic Association between Vitamin D Receptor (VDR) Gene and Parkinson Disease (P4.055)

OBJECTIVE: To investigate the role of vitamin D (vit D) and vit D-gene interaction in affecting risk for PD. BACKGROUND: Total plasma vit D concentrations have been inversely associated with risk of PD. Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene, which encodes the major mediator of vit D’s biological actions, are also associated with PD in multiple studies, but not consistently. We hypothesize that this is because the genetic effects of VDR are modified by vit D concentrations. We also analyzed association of PD with vit D from different sources, i.e. vit D2 (diet and supplement) and vit D3 (mainly sunlight), separately. DESIGN: Mass Spectrometry was used to measure vit D2 and D3 in stored plasma samples of 484 PD cases and 409 controls studied in our previous genome-wide association study. Total vit D=vit D2+vit D3. RESULTS: Vit D deficiency (total vit D =20 ng/mL) [OR=0.6 (0.5-0.84) and 1.7 (1.3-2.3)] but not in the vit D deficient stratum [OR= 1.6 (0.9-3.1) and 1.0 (0.6-1.7)]. CONCLUSION: Our data not only strongly support vit D deficiency as a risk factor for PD but also demonstrate that vit D2, which can only be obtained via dietary source, is inversely associated with risk of PD, suggesting that vit D deficiency is not secondary to lack of sunlight exposure in PD patients. We also demonstrate that the effect of VDR polymorphisms on PD depends on vit D concentration, which provides a potential explanation of the inconsistency across different genetic studies where vit D concentration was not considered. Disclosure: Dr. Wang has nothing to disclose. Dr. Vance has received personal compensation for activities with Covance. Dr. Vance has received royalty payments from Athena Diagnostics. Dr. Vance has received research support from the National Institutes of Health. Dr. Evatt has received research support from Santhera, Merz Pharma, Ipsen, Boehringer Ingelheim Pharmaceuticals, Inc., UCB Pharma, and Biotie Therapies. Dr. Maldonado has nothing to disclose. Dr. Perry has nothing to disclose. Dr. Ritchie has received personal compensation for activities with Beckman Coulter. Dr. Beecham has nothing to disclose. Dr. Martin has nothing to disclose. Dr. Haines has nothing to disclose. Dr. Pericak-Vance has received personal compensation for activities with the University of Alaska. Dr. Scott has nothing to disclose