8/28/2017. Behind the Scenes of Parkinson s Disease

Transcription

1 BEHIND THE SCENCES IN Parkinson s Disease Behind the Scenes of Parkinson s Disease Anna Marie Wellins DNP, ANP C Objectives Describe prevalence of Parkinson's disease (PD) Describe the hallmark pathologic brain changes that occur in PD Describe risk factors and /or prodromal symptoms associated in the development of PD List the cardinal motor and non motor symptoms in the diagnosis of PD Describe the stages of PD Outline pharmacological modalities for PD to include common side effects List possible differential diagnosis in PD Identify potential complications and management associated with PD Identify emerging treatment modalities and research in the treatment of PD Discuss use of Deep Brain Stimulation in PD Parkinson disease is a progressive disorder of the nervous system. The disorder affects several regions of the brain, especially an area called the substantia nigra that controls balance and movement. 1

2 Parkinson's Disease Neurodegenerative pathology caused by abnormal degeneration of dopaminergic neurons in the ventral tegmental area and substantia nigra pars compacta in the midbrain resulting in damage to the basal ganglia OVERVIEW Parkinson's disease (PD) is a common neurodegenerative disorder demonstrating age related prevalence with 1% of the population affected over the age of 60 and 4% at age 85. It' s prevalence is second only to Alzheimer's Disease. The significance of this disease is tremendous affecting function, quality of life and caregiver burden. The impact includes major financial burdens and health care costs. Although it's cause remains unknown it is very important that Practitioners increase awareness of this complex disease and its management. It is important to understand associated pathophysiology, motor and non motor symptomology, timely diagnosis, management, common challenges, medication modalities along with new and promising treatments. Mitigating complications is essential in caring for this patient population, especially when hospitalized. Also important, is an understanding of current research that is being done for PD Pathophysiology Pathological hallmark of classical PD comprises: Loss of nigrostriatal dopaminergic neurons in the substantia nigra pars compacta SNc Alpha synuclein (a Syn) containing Lewy bodies in the surviving neurons (proteinpathy) Dopamine allows transmission of signals from the substania nigra to the corpis striatum to produce smooth, purposeful movement 2

3 Genetic Most cases of Parkinson disease probably result from a complex interaction of environmental and genetic factors. These cases are classified as sporadic and occur in people with no apparent history of the disorder in their family. The cause of these sporadic cases remains unclear. Genetics Approximately 15 percent of people with Parkinson disease have a family history of this disorder. Familial cases of Parkinson disease can be caused by mutations in the LRRK2, PARK7, PINK1, PRKN, or SNCA gene, or by alterations in genes that have not been identified Mutations in some of these genes may also play a role in cases that appear to be sporadic (not inherited) Premotor Symptoms Prior to Onset of PD Olfactory Dysfunction Loss of smell (hyposomnia) Neuropsychiatric Premorbid Personality (limited data), Depression/Anxiety Sleep Rapid Eye Movement Sleep Behavior Disorder (RBD), Excessive Daytime Sleepiness (EDS), Restless Leg Syndrome (RLS) GI Constipation Autonomic Orthostatic Hypotension, Erectile Dysfunction (ED) 3

4 Epidemiological Exposure to pesticides risk Caffeine consumption and smoking are associated with risk Neurotoxins MPTP industrial chemical and contaminant of illicit narcotics, heavy metal manganese Oxidative stress/free radicals Cardinal Motor Signs in Parkinson s Disease Tremor Bradykinesia Muscular Rigidity Postural Instability Differential Diagnosis Atypical Parkinson s Disease Multiple System Atrophy Dementia with Lewy bodies Progression supranuclear palsy Corticobasal degeneration 4

5 Motor Features Craniofacial: Masked facial expression (Hypomimia) Decreased eye blinking Speech Impairment (hypokinetic dysarthria, hypophonia, palilalia) Dysphagia Sialorrhea (hyper salivation) Motor Features Visual: Blurred vision Impaired contrast sensitivity Hypo metric saccades (slow eye movements) Impaired vestibulo ocular reflex ( normal eye movement in direction opposite of head movement) Impaired upward gaze and convergence Eyelid opening apraxia Motor Features Musculoskeletal: Micrographia Myoclonus (muscle jerking) Stooped Posture Severe anterior flexion of thoracolumbar spine Pisa Syndrome (lateral flexion of spine) Difficulty turning in bed 5

6 Motor Features: Gait Shuffling, short stepped gait Freezing Limited arm swing 6

7 Parkinson Disease Rating Scale (UPDRS) I. Mentation, behavior and mood Intellectual impairment Thought disorders: vivid dreams/hallucinations Depression Motivation/initiative II. ADL s Speech Salivation Swallowing Handwriting Cutting food/handling utensils Dressing Hygiene Turning in bed and adjusting bed clothes Falling Freezing when walking Walking Tremor Sensory complaints Parkinson Disease Rating Scale (UPDRS) III. Motor exam Speech Facial expression Tremor at rest Action or postural tremor of hands Rigidity (passive movement of major joints) Finger taps Hand movements Arising from chair Posture Gait Postural stability (retropulsion) Body bradykinesias and hypokinesia (slowness, hesitancy, decreased arm swing, small amplitude and poverty of movement) 7

8 Parkinson Disease Rating Scale (UPDRS) III. Complications of therapy Dyskinesias (duration, disability, pain) Early morning dystonia Clinical fluctuations on/off periods Definitions Dyskinesia: Involuntary movements Dystonia: Abnormal cramps and postures of cervical spine, extremities and trunk Apraxia: Difficulty in performing tasks or movements when asked Akathisia: Condition of restlessness and urgent need to move 8

9 NON MOTOR Symptom Management Depression, mood disorders, anxiety disorders, apathy, and fatigue Cognitive dysfunction and dementia Psychosis Medication related impulse controls disorders and other compulsive behaviors Autonomic dysfunction: Orthostatic hypotension Sexual dysfunction Gastrointestinal dysfunction Sialorrhea Sweating Disorders of sleep and wakefulness: RBD Sleep fragmentation and insomnia Daytime Sleepiness and sudden onset of sleep. PD and Hospitalization Pt s with Parkinson s are hospitalized 50 % more than their peers without Parkinson s 75% of Pt s do not receive their medications on time while in hospital Pt s suffer avoidable complications with longer hospital stays Hospitals and staff lack understanding of PD including importance of medication timing and adverse effects of commonly administered medications Hospitals may not stock all PD medications Lack of awareness that poorly managed PD results in mental confusion, worsening symptoms, falls and aspirations TREATMENT MODALITIES The effect of disease on the dominant hand The degree to which the disease interferes with work, activities of daily living, or social and leisure function The presence of significant bradykinesia or gait disturbance Patient values and preferences regarding the use of medications 9

10 Common Medications for PD LEVODOPA Sinemet CR (carbidopa/levodopa) 25/100 Q8hrs Stalevo (carbidopa/levodopa/entacaone) 25/100/200 Q8hrs Carbidopa prevents conversion of levodopa into dopamine except in the brain Reduces tremor, bradykinesia and rigidity Titration of dosage, frequency Reduce off effects Side effects: nausea, hypotension, drowsiness, sudden sleep onset Long term effects: hallucinations/psychosis Postponing levodopa unproven DOPAMINE AGONISTS Pramipexole: titrate TID dosing of max dose 4.5mg/day Ropinirole: titrate TID dosing of max dose of 24mg/day Bromocriptine: titrate BID dosing of max dose of 100mg/day Transdermal rotigotine Apomorphine injection Monotherapy in younger pts with PD Titrate dose slowly Effective in pts with motor complications and dyskinesia's Side effects: nausea, sleepiness, orthostatic hypotension Impulse control disorders/dopaminergic dysregulation syndrome Withdrawal symptoms can resemble cocaine withdrawal in 8 19% of pts MAO Inhibitors Selective MAO Inhibitors: Selegiline 5mg BID with 2 nd dose at 12noon to minimize insomnia Rasagiline monotherapy 1mg daily Inhibits dopamine breakdown Does not precipitate a hypertensive crisis with ingestion of tyramine containing foods 10

11 ANTICHOLINGERICS Dopamine depletion produces cholinergic sensitivity Most useful as monotherapy for pts <70 with disturbing tremor but do not have significant bradykinesia or gait disturbances Also useful in pts who have persistent tremor despite tx with levodopa or dopamine agonists Trihexyphenidyl mg BID with gradual increase to 2 mg TID Avoid use in older pts with cognitive/memory impairment, confusion or hallucinations Tx sialorrhea or urinary frequency with peripherally acting agents such as`propantheline Class side effects: dry mouth, blurred vision, constipation, nausea, urinary retention AMANTADINE Antiviral agent with mild antiparkinsonian activity, mechanism of action uncertain; does increase dopamine release, inhibit dopamine reuptake, stimulates dopamine receptors and may exert central anticholinergic effects Divided doses mg daily Adverse effects: ankle edema confusion, hallucinations, nightmares more likely when used with other PD drugs COMT INHIBITORS (catechol O methyl transferase) Levodopa extenders Tolcapone 100mg TID (monitor LFTs) Entacapone 200mg with each dose of levodopa (up to 8x daily) Mainly used to treat pts with motor fluctuations wearing off periods Common side effects: dyskinesia, hallucinations, confusion, nausea, orthostatic hypotension SE managed by lowering levodopa doses prior to addition 11

12 Supportive Care EXERCISE/PHYSICAL THERAPY SUPPORT GROUPS DIET QOL PREVENTION OF COMPLICATIONS FALL and INJURY PREVENTION MANAGING SYMPTOMS ADJUSTING MEDICATIONS MANAGING DEPRESSION END OF LIFE CARE/PALLIATIVE ASSITING CARE GIVERS Deep Brain Stimulator Deep brain stimulation (DBS) is a neurosurgical procedure involving the implantation of a medical device called a brain pacemaker, which sends electrical impulses, through implanted electrodes, to specific parts of the brain (brain nucleus) for the treatment of movement and affective disorders. Criteria for Deep Brain Stimulation Clear dx of PD (not atypical PD) Age 75 Intact cognitive function Demonstrated motor improvement with sinemet Lack of comorbidities Development of significant motor fluctuations/dyskinesia Degree of disability Realistic expectations Screening MRI to r/o severe vascular disease Ability to cooperate and be awake during surgery 12

13 Carbidopa/Levodopa Suspension (Duopa) duodenal infusion (PEG tube) Pump provides continuous dosing of medication for pt s with advanced PD who experience marked motor fluctuations and dyskinesias (especially night time symptoms) Pump bulky Need to care for peg tube site and manage pump APOMORHINE PUMP Dopamine agonist SQ infusion for: sudden and unpredictable changes in symptoms severe off periods that aren t controlled by other Parkinson s medications Transcranial Magnetic Stimulation 13

14 Magnetic Therapy Electromagnetic therapy is a non invasive and safe approach for the management of Parkinson s disease Electromagnetic therapy can help alleviate motor and non motor deficits that characterize Parkinson s disease. 14