6/13/2017 PROFESSOR CHRISTOPHER J MATHIAS. Non-motor features in PD AUTONOMIC NERVOUS SYSTEM. Motor. Non-Motor CLINICAL AUTONOMIC MANIFESTATIONS

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1 PRFESSR CRISTPER J MATIAS Autonomic & Neurovascular Medicine Centre and The Joint ypermobility Unit, ospital of St John & St Elizabeth, St Johns Wood, London Autonomic Dysfunction in Parkinsons Disease: Recognition, Evaluation and Treatment Professor Christopher J. Mathias DPhil DSc FRCP FMedSci Institute of Neurology, University College London Autonomic Unit, National ospital for Neurology & Neurosurgery Queen Square Neurovascular & Autonomic Medicine, The Lindo Wing Imperial College NS ealthcare Trust at St Mary s ospital, London Non-motor features in PD AUTNMIC NERVUS SYSTEM Motor *CvAD=Cardiovascular Autonomic Dysfunction Parkinson s Disease Psychiatric symptoms Non-Motor Autonomic CvA D Sleep disorders lfactory dysfunction CLINICAL AUTNMIC MANIFESTATINS orthostatic (postural) hypotension anhidrosis, heat intolerance Alimentary tract oro-pharyngeal dysphagia, constipation Urinary nocturia, frequency, urgency, incontinence, retention Reproductive erectile and ejaculatory failure Respiratory stridor, inspiratory gasps, apnoea cular aniscoria, orner s syndrome 1

2 AUTNMIC CNTRL F BP & R Blood Pressure Arterial Baroreceptors Carotid Sinus Central Nervous System Aortic Arch Parasympathetic utput Cardiac utput Cardiopulmonary Baroreceptors Blood Vessels Total Peripheral Resistance RTSTATIC YPTENSIN Noradrenaline (pg/ml) Adrenaline (pg/ml) g/ml) Plasma noradrenaline and adrenaline levels 24 hour Ambulatory BP & R autonomic profiling (London Autonomic Protocol) 24 hour BP and R monitoring out of the clinical setting A diary with a structured schedule of autonomic focused activities, designed to provoke changes in BP and R, to include standing, food and exercise Nocturnal circadian rhythm 2

3 eart Rate (Beats/Min) eart Rate (Beats/Min) Blood Pressure (mmg) Blood Pressure (mmg) 6/13/217 NRMAL SUBJECT: 24 R BP & R PRFILE using the London Autonomic Centre protocol AUTNMIC FAILURE: 24 R BP & R PRFILE using the London autonomic protocol 2 In Bed 2 Systolic In Bed Systolic Diastolic Sample Time/24 h 5 Diastolic Sample Time/24 h Sample Time/24 h Sample Time/24 h RTSTATIC YPTENSIN IN PD Major non-motor feature Troublesome symptoms Devastating sequelae falls, fractures Treating Enables better treatment of motor features W CMMN IS IN PD? Rare to 59% (39% symptomatic) What age? What stage? relentlessly progressive unpredictably progressive Which drugs? Which physician? SYMPTMS F Cerebral ypoperfusion Dizziness Visual disturbances Loss of consciousness Cognitive defects Muscle ypoperfusion Coat hanger ache Renal ypoperfusion liguria Non-specific Weakness, lethargy, fatigue Falls 3

4 79-year old FACTRS TAT CAN WRSEN Fall complicated by humeral fracture. No evaluation of the causes of fall was carried out. Surgical treatment excluded because of advanced age. Time of day (worse in the morning) Prolonged recumbency Warm environment (hot weather, central heating, hot bath) Raising intrathoracic pressure (micturition, defaecation, coughing) Food and alcohol ingestion Physical exertion Drugs (dopaminergic agents) FD INTAKE AND BLD PRESSURE Systolic and diastolic blood pressure (mmg) BLD PRESSURE CANGES WIT EXERCISE 4 Change 3 in systolic 2 BP W 5W 75W Controls MSA PAF Time (min) post 2 post 5 post 1 Time (min) IATRGENIC RTSTATIC YPTENSIN BP BP mmg 25 mmg 15/8/211 Selegiline 1 mg od, Sinemet Plus 1 tab qds, Fludrocortisone 2 mg od, Solifenacin 5 mg od, Tamsulosin MR 4 mg od 29/9/ year-old man with parkinsonism and lightheadness CLINICAL MANIFESTATINS rthostatic (postural) hypotension 25 ff medication 4

5 SUDMTR AUTNMIC DYSFUNCTIN IN PD yperhidrosis ypohidrosis and heat intolerance CLINICAL MANIFESTATINS rthostatic (postural) hypotension Alimentary tract ro-pharyngeal dysphagia, constipation SALIVARY SECRETIN IN PD Too little or none (hypostomia or xerostomia) autonomic failure: rare in MSA anticholinergic drugs Excessive impaired clearance oropharyngeal dysphagia 5

6 CLINICAL MANIFESTATINS rthostatic (postural) hypotension Alimentary tract ro-pharyngeal dysphagia, constipation Urinary Nocturia, frequency, urgency, incontinence, retention CLINICAL MANIFESTATINS rthostatic (postural) hypotension Alimentary tract ro-pharyngeal dysphagia, constipation Urinary Nocturia, frequency, urgency, incontinence, retention Reproductive Erectile and ejaculatory failure CLINICAL MANIFESTATINS rthostatic (postural) hypotension Alimentary tract ro-pharyngeal dysphagia, constipation Urinary Nocturia, frequency, urgency, incontinence, retention Reproductive Erectile and ejaculatory failure cular Aniscoria, orner s syndrome 6

7 LGICAL TERAPY MANAGEMENT F RTSTATIC YPTENSIN Non-pharmacological Pharmacotherapy RTSTATIC YPTENSIN TREATMENT F RTSTATIC YPTENSIN Non-pharmacological To avoid To introduce To consider A 21 st Century Water Cure! Mathias CJ The Lancet 2; 356:

8 Mean reduction in orthostatic fall in SBP, mm g 6/13/217 TREATMENT F RTSTATIC YPTENSIN Non-pharmacological To avoid To introduce To consider Pharmacological TREATMENT F RTSTATIC YPTENSIN Non-pharmacological Pharmacological Starter - fludrocortisone Sympathomimetics - ephedrine, midodrine, L-DPS Targeting - octreotide: post-prandial hypotension - desmopressin: nocturnal polyuria - erythropoietin: anaemia - pyridostigmine: ganglia stimulation L-DPS (DRXIDPA; NRTERA) Levodopa Dopamine N C Dopa Decarboxylase N L-DPS N N C Noradrenaline DRXIDPA-PASE IIB STUDY Reduction in rthostatic Fall in SBP, Day to Day Droxidopa 1 mg t.i.d. Droxidopa 2 mg t.i.d. Droxidopa 3 mg t.i.d. Placebo verall Parkinson's disease *MSA 8

9 Number of Falls 6/13/217 N36A: EFFECT F DRXIDPA N CUMULATIVE FALLS Why Treat? Droxidopa (n=24) Placebo (n=27) Total falls = 197 Total falls = 79 Number of Days of Therapy 49 Spontaneously Reported Patient Falls in Chelsea Trials Placebo n = 197 Northera n = 79 AUTNMIC DYSFUNCTIN AND IN PD Mov Disord. E-pub 217 Common Recognised Investigated Precisely evaluated Personalised treatment ENR. 217; 12(1) Autonomic Dysfunction in Parkinsons Disease: Recognition, Evaluation and Treatment Professor Christopher J. Mathias Dphil DSc FRCP FMedSci 9