Parkinson s Disease and Multiple System Atrophy

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1 Parkinson s Disease and Multiple System Atrophy Jalesh N. Panicker MD, FRCP Department of Uro-Neurology National Hospital for Neurology and Neurosurgery and UCL Institute of Neurology Queen Square, London Neurogenicbladdercourse

2

3

4 Mov Disord Jul;21(7):

5 Movement Disorders 2007; 22: n=545

6 Araki and Kuno, 2000

7 Uchiyama et al. 2011

8 dstrong.blog.uvm.edu - + Does dopamine modulate the normal micturition reflex?

9 PD-related OAB Vascular disease Pedal oedema Prostatic enlargement Cervical spondylosis and myelopathy Diabetes mellitus congestive cardiac failure Obstructive sleep apnea syndrome Sleep disturbances medications: diuretics

10 Incontinence: is it always due to an overactive bladder? Overactivity Stress incontinence Overflow Functional: Mobility, toilet access Cognitive impairment: visuospatial disorientation, memory, aphasia, compulsive behaviour, social inhibition, apraxia

11 (ml) Nocturnal polyuria in PD (n=17) Day-time Night-time x1 x2 x3 > x4 Night-time frequency Percentage nocturnal urine output found also to increase with increasing night time frequency

12 Is it Multiple System Atrophy (MSA)?

13 Parkinsonism Parkinson s Disease Parkinson -Plus Secondary Parkinsonism

14 MSA Beck et al., 1994

15 Detrusor overactivity Open bladder neck Incomplete bladder emptying EMG: reninnervation Sphincter insufficiency

16 Onset of urogenital dysfunction Bladder dysfunction MSA May precede other neurological deficits Early and severe incontinence. Overactive bladder symptoms stage of chronic urinary retention Usually follows PD Less severe incontinence. Overactive bladder symptoms, nocturnal polyuria Bladder scan Elevated postvoid residual early in the course Usually normal Videourodynamics DO, acontractile detrusor Open bladder neck may be seen DO, acontractile detrusor pseudodyssynergia Sexual dysfunction Erectile dysfunction (often first manifestation) ED, sometimes sexual compulsive behaviour

17 Levodopa: being on and off Storage symptoms Voiding symptoms Off Urgency, incontinence Voiding dysfunction On Mixed: urgency worse in most, may be better Improved Sakakibara et al, 2002

18 Deep Brain Stimulation (DBS) Most commonly: subthalamic nucleus Improved motor symptoms; reduced dopaminergic medications Improved OAB symptoms Nocturia (Winge and Nielson 2012) Enhanced processing of afferent bladder signalling (Herzog et al. 2008)

19

20 The anticholinergic burden High >15 pmol/l Amitriptyline Doxepin Clozapine Atropine Dicyclamine tolterodine Moderate 5 15pmol/L Nortriptyline Paroxetine Chlorpromazine Olanzapine oxybutynin Mild pmol/l Citalopram Escitalopram Fluoxetine Mirtazepine Quetiapine Temazepam Ranitidine Courtesy Adrian Wagg Adapted from Gerretsen P, Pollock BG Drugs Ageing 2011

21 The blood brain barrier

22 Efflux across the BBB by P-gp active transport Brain Blood-brain barrier diagram tight junction drug endothelium Blood passive diffusion Efflux of antimuscarinics: passive diffusion P-gp active transport mechanism Active transport mechanism: permeability-glycoprotein (P-gp) Lower levels than would be expected for its lipophilicity Diagram courtesy Vicki Burd 1.Ramakrishnan P. EQJBM. 2003; 19: ; 2. Wagg A et al. IJCP. 2010; 64(9): ; 3. Chancellor et al. Drugs Aging. 2012; 29(4):

23 Antimuscarinic Chemical structure (type of amine) Lipophilicity P-gp substrate Oxybutynin Tertiary High No Darifenacin Tertiary Moderate Yes Solifenacin Tertiary Low-Moderate No Tolterodine Tertiary Low-Moderate No Fesoterodine Tertiary Low-Moderate Yes Trospium Quaternary Very Low/Hydrophilic Yes Table courtesy Vicki Burd 1.Ramakrishnan P. EQJBM. 2003; 19: ; 2. Wagg A et al. IJCP. 2010; 64(9): ; 3. Chancellor et al. Drugs Aging. 2012; 29(4):

24 M3 receptor selectivity and Darifenacin

25 MCC Botulinum toxin in Parkinson s disease Giannantoni et al. 2011

26 PD n=9; 100U onabot PD n=20; 100U onabot

27 Giannantoni et al Post void residual

28 Tibial Nerve Stimulation percutaneous (PTNS) and transcutaneous Courtesy Uroplasty

29 2009

30 Conclusions PD and MSA- LUTD common and has a dynamic course Several treatment options available Challenge to manage

31 Two teaching courses Sexual Dysfunction in MS and other neurological disorders September 29, 2014 at Queen Square Practical management of sexual dysfunction in the neurological patient Neurogenic bladder course November 27 and 28, 2014 at Queen Square Approach and management of bladder, bowel and sexual dysfunction in the neurological patient

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