CDM 4 Exam 2 Review Parkinson s disease I What is PD A Chronic progressive motor function disorder B Primary or idiopathic Parkinsonism C Epidemiology Incidence 446 cases 100 000 people 1 2 1 prevalence 60 years and older 3 Mean age at diagnosis 55 60 yrs 4 Male gender 1 5 times greater risk than females II Etiology A Environmental factors 1 Rural well water farms pesticide exposure elevated risk for PD 2 Smoking and caffeine protective 3 large cups of coffee Lewy body formation a Modest PD symptom improvement excessive daytime somnolence B Occupational factors copper lead iron insecticides C Genetic factors 1 relatives diagnosis before age 50 now 24 identified gene mutations associated with PD risk D Exact underlying cause unknown E Neurodegeneration 1 Apoptosis 2 Neurotoxins MPTP MAO B MPP toxic metabolite 3 Free radical production DA metabolism hydrogen peroxide 4 Lewy body formation existence poorly understood presence is diagnostic for PD III Pathophysiology of Parkinsons Motor symptoms A Extrapyramidal Motor System EPMS 1 Responsible for coordination of Striatum learned movement 2 Composed of the basal ganglia Caudate nucleus Putamen Globus Pallidus 3 Get input from the substantia nigra B Neuronal communication 1 Substantia nigra striatium synthesis storage transport DA 2 Striatum thalamocortical pathway direct and indirect pathways C Neurotransmitters GABA inhibitory Glutamine excitatior Ach D Neuronal Communication in a normal Pt E Degenration of dopaminergic cells in the substantia nigra F Depletion of DA SNC worsening motor symptoms D1 1 1 5 per decade in normal adults 2 45 in first decade in PD G Degree of DA depletion correlates w symptom severity H Several other NT are also affected by PD 1 Ach GABA glutamate NE 5HT IV Clinical Presentation A Sensory symptoms confusion sleep disturbances may appear initially B Classic clinical features TRAP 1 T remor 2 R igidity 3 A kinesia absence of movement or bradykinesia slow movement when starting movement 4 P ostural instability C Resting Tremor 1 Typical presenting symptom on diagnosis begins in unilateral one site extremity 2 Described as pill rolling a Not the shaky hand hyperthyroid too much caffeine tremor 3 May cease during voluntary movement 4 Can be exacerbated by stress 5 Disappears during sleep D Rigidity 1 Cogwheel in nature a During passive range of motion of a limb b Muscle stiffness weakness c Stop and go effect 2 Impairment of activities of daily living a Getting dressed In out of bed E Akinesia or Bradykinesia 1 Akinesia absence of movement a Slow to initiate movement up out of a chair Freezing 2 Bradykinesia slowness of movement a Slow shuffling gait b Handwriting becomes smaller c Decreased arm swing d Decreased swallowing e Masked faces F Postural Instability 1 Symptom of Advanced disease 2 Frequent falls and injury 3 Loss of center of gravity a Tendency to fall forward festination b Falling backwards restropulsion c Pull test d Pharmacologic therapy largely ineffective V Estimating Disease Severity A Modified Hoehn and Yahr Staging 1 Stage 0 no signs of disease 2 Stage 1 unilateral disease 3 Stage 1 5 unilateral with axial involvement 4 Stage 2 bilateral disease w o balance impairmenr 5 Stage 2 5 mild bilateral disease with recovery on pull test 6 Stage 3 mild to moderate bilateral disease some postural instability physically independent 2 7 Stage 4 sever disability unable to live alone independently 8 Stage 5 unable to walk or stand without assistance B United Parkinson s disease rating scale UPDRS VI Diagnosis and treatment A Rule out other movement disorders med induced essential tremor etc B Diagnosis based on clinical symptoms C Treatment approaches 1 Neuroimaging techniques not conclusive 2 Presence of Bradykinesia tremor or rigidity 1 Nonpharmacologic exercise voice training evidence 2 Pharmacologic 3 Surgery VII Drug therapy initiation A When to start what to use B Early PD treatment 1 Patient age young vs older 65 2 Early vs advanced disease previous PD therapy 3 Symptoms present severity cognitive or functionally impaired 1 Several studies support this stabilization of symptoms and QOL 2 ELLDOPA levodopa vs placebo symptoms but uptake 3 DATATOP selegiline vitamin E delayed need for levodopa 4 Anticholincergics and amantadine younger minor PD symptoms tremor 5 Evolving role of DA agonists vs levodopa pros cons of early agonists vs levodopa use 6 Dopamine agonists younger no functional or cognitive impairment 7 Carbidopa levodopa elderly or poor cognition functionally impaired 1 TEMPO rasagiline functional decline in early vs delayed start patients minimize C Early neuroprotective PD treatment 2 ADAGIO similar to TEMPO design rasagiline larger N 1 5 years early vs delayed early formation of free radicals 1mg day NOT 2mg day superior 3 CALM PD REAL PET D Advanced PD tretment 1 Agonist monotherapy worsening symptoms a dose add Sinemet b No evidence for adding selegiline COMT I 2 Motor fluctuations with sinemet s sx of Parkinsons even though on medication a Absence of peak dose dyskinesias i Add DA agonist COMTI or MAOBI ii More frequent admin or increase dose of levodopa iii Switch from IR to CR formulation or admin of intrajejunal suspension b Presence of peak dose dyskinesias i Balancing on off time with dyskinesias ii IR form provides better dosing control iii Decrease dose try COMTI or addition of DA agonist iv Treatment with amantidine VIII Non pharmacologic treatments A Nutrition protein re distribution B Support Social peer family support C Exercise 3 D Education family and patient E Surgery 1 Deep brain stimulation DBS a Most promising non ablative b Best for drug refractory tremors 2 CNS lesions thalamotomy pallidotomy subthalamic nucleus lesions a Improves rigidity tremor and akinesia 3 Grafting transplantation investigational IX Non motor PD symptoms A Sleep disorders incontinence constipation dysphagia drooling sweating temperature intolerance ED paresthesias dementia anxiety depression seborrheic dermatitis visual deficits orthostatic hypotension B Under recognized and under treated medication ADE vs disease complications C AAN guidelines D Evidence supports sildenafil for ED carbidopa levodopa for RLS restless leg syndrome E Dementia and Psychosis in PD patients 1 Complication of disease progression up to 40 incidence in advanced disease 2 Drug induced a Simplify drug regimen b D C meds of least likely clinical benefit and highest risk of psychosis i Anticholinergics ii Selegiline MAOI