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Parkinson's Disease by Sir William Richard Gowers 1886

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Parkinson's Disease by Sir William Richard Gowers 1886 Cardinal Features An Overview of • Parkinsonism Parkinson’s Disease 9 Bradykinesia 9 Rigidity 9 Tremor Punit Agrawal, DO • Classically at rest Division of Movement Disorders 9 Postural instability OSU Dept of Neurology • Typically a late symptom Illustration of Parkinson's Disease by Sir William Richard Gowers 1886. (http://commons.wikimedia.org/wiki/File:Sir_William_Richard_Gowers_Parkinson_Disease_sketch_1886.jpg) • Parkinson’s Disease accounts for about 85% of patients with features of parkinsonism - (wemove.org) Parkinson’s Disease Cardinal Features of Parkinsonism - Bradykinesia • In 1817 James Parkinson • Delayed motor initiation (1755-1824) described Parkinson’s disease. • Slowed voluntary movement • Rapid fatigue with repetitive movements • Shuffling gait • Micrographia • Decreased dexterity • Hypomimia (decreased facial expression) Parkinson J (1817) An essay on the Shaking palsy. Sherwood, Neely and Jones, London • Hypophonia (low voice volume) 1 Cardinal Features of Cardinal Features of Parkinsonism - Parkinsonism - Tremor Postural Instability • Loss of postural reflexes • Classically, a 3-7 Hz rhythmic resting • Retropulsion tremor that commonly presents with opposition of forefinger and thumb. • Increased difficulty turning with increased incidence of falls • Hands, legs, lips/chin. • Often the most disabling and least • Rest tremor typically increases with walking and distraction, but decreases with responsive to medications attention or with action. • Not typically present as an early features of Parkinson’s disease. Parkinson’s Disease can cause Cardinal Features of numerous other symptoms including Parkinsonism - Rigidity many non-motor MOTOR NON-MOTOR • Bradykinesia • Constipation • Involuntary increase in muscle tone • Rigidity • Anosmia (loss of smell) Cardinal • Tremor • Excessive drooling Features • Gastroesophageal Reflux • Postural instability • Lead pipe or cogwheel • Depression/ Anxiety • Micrographia (small writing) • Cognitive changes/dementia • In mild disease, can augment with • Decreased dexterity • Sleep disturbance activation of opposite limb (Froment’s • Hypomimia (“Masked Face”) • Seborrheic dermatitis • Postural changes • Bladder urgency/frequency maneuver) • Festination/Freezing of gait • Sweating spells • Speech changes • Hypotension • Dysphagia (trouble • Sexual dysfunction swallowing) 2 Pathological Hallmark of PD Braak Staging of Lewy Bodies Classic hallmark is degeneration of dopamine neurons from the substantia nigra pars compacta plus intracytoplasmic proteinaceous inclusions (Lewy bodies). Per decade of life, there is an estimated 9-13% loss of Braak H, et al. J Neurology. 2002;249(suppl 3):1432-1459. dopamine neurons. Stage 1 - Lewy bodies (LB) first form within the olfactory bulb and dorsal motor nucleus of the vagal nerve. Motor symptoms do not Stages 2 and 3 - LB pathology expands into additional brain stem nuclei (e.g., locus appear until there is a lost of coeruleus and substantia nigra). about 70% of dopaminergic Stages 5 and 6 - Pathology extends into the cerebral cortex. neurons from this area. More commonly recognized clinical symptoms arise during Stages 4 to 6 when the http://www.smbs.buffalo.edu/pth600/IMC-Path/y2case/y2ans18.htm pathology involves significant regions of the substantia nigra and related brain areas. PD Pathology Epidemiology • PD also associated with extensive pathology in • As many as 1.5 million people in the US have non dopamine cells: Parkinson’s disease. 9 Cholinergic neurons in the nucleus basalis of • Approximately 60,000 Americans are diagnosed Meynert and dorsal motor nucleus of vagus with Parkinson's disease each year. 9 Norepinephrine neurons in the locus ceruleus • Affects 1.5 -2.0 % of people over the age of 60 9 Serotonin neurons in the midline raphe years. 9 plus many other cells in the cortex, spinal • Onset of symptoms is typically 60-70 years of cord, and peripheral autonomic system. age, but up to 15 % of people with PD are diagnosed before the age of 50. • Pathology in the dorsal motor nucleus and 9 These estimates do not account for cases of olfactory regions may predate dopaminergic cell PD that are unreported, undiagnosed or loss in the substantia nigra pars compacta. misdiagnosed. Forno LS. Neuropathy of Parkinson’s Disease. J Neuropathol Exp Neurol 1996;55:259-272. Braak H, et al. J Neurology. 2002;249(suppl 3):1432-1459. National Parkinson’s Disease Foundation, Inc. 2007 3 NINDS Parkinson’s Etiology Disease Criteria (aka Gilman Criteria) • The cause is not known, and with most cases of • Group A: (at least 2 needed) disease being sporadic. 9 Resting tremor* • However, there is a suspected strong link to 9 Bradykinesia* 9 Rigidity genetic and environmental factors. 9 Asymmetric onset • Risk factors included family history, increasing 9 Postural instability age, rural living, well water, exposure to • Group B: Suggests alternative diagnosis: pesticides/herbicides, and repeated head injury. 9 Early postural instability 9 Early freezing of gait • Some studies have suggested smoking decreases 9 Hallucinations risk of development of Parkinson’s disease with 9 Early dementia no good explanation. 9 Gaze palsy 9 Early, severe dysautonomia 9 Previous condition/drugs known to cause parkinsonism Parkinsonism – Diagnosis of PD Differential Diagnosis • Parkinson’s disease is a clinical diagnosis based • Parkinsonism does not equal Parkinson’s disease. on history and exam findings. • The differential for parkinsonism include: • The diagnosis of parkinsonism is classified as: 9 Atypical Parkinsonian Syndromes 9 Most Likely - 2 of 4 present cardinal features, 9 Secondary Parkinsonism with 1 being resting tremor or rigidity. • Vascular • Medication induced 9 Probable – isolated rest tremor or rigidity • Infectious alone. • Metabolic/Toxic 9 Possible - either bradykinesia or postural 9 Dementia syndromes instability 9 Other Hereditary degenerative disease 9 Psychogenic 4 Features that may suggest cause of parkinsonism other than Atypical Parkinsonian Parkinson’s disease Syndromes 9 Symmetric symptoms 9 Early balance/gait trouble or falling 9 Early symptoms of cognitive dysfunction or dementia symptoms • Progressive Supranuclear Palsy that precede onset of features of parkinsonism or within 1 year of motor symptoms. • Cortico-basalganglionic Degeneration 9 Minimal to no response to levodopa 9 History of exposure to drugs reported to cause parkinsonism - Neuroleptics • Multiple System Atrophy - Lithium - Depakote 9 MSA type P: (Striatonigral Degeneration) -Other 9 MSA type A: (Shy-Drager Syndrome) 9 Stepwise progression or history of CVA 9 Apraxia or alien limb phenomena 9 MSA type C: (Olivopontocerebellar Atrophy) 9 Vertical gaze palsy 9 Upper motor neuron symptoms on exam Testing? Progressive Supranuclear Palsy • There is no diagnostic test used to diagnose PD • Neuroimaging and blood tests are useful to rule out other • Fairly symmetrical symptoms possible conditions if tremor or history/exam is atypical with features that may suggest a diagnosis other than • Early onset of gait trouble with falls Parkinson’s Disease: • Axial rigidity 9 Work up may include: • Thyroid profile • Early dysarthria and gaze impairment • Ceruloplasmin/Serum copper 9 Vertical gaze palsy • Brain imaging • Frontal lobe dementia • EMG/NCV • Minimal tremor • Confirmation of a diagnosis of Parkinson’s disease can be made at autopsy • Minimal to no response to levodopa. 5 Corticobasalganglionic Secondary Parkinsonism • Vascular Degeneration • Usually history of acute onset or step wise progression • Predominant gait trouble and possible cognitive deficits • Cortical apraxia and possible alien hand • Supported by brain MRI findings of previous infarcts • Medication induced syndrome 9 Typically dopamine blocking agents, but others have been more more commonly reported as well • Rigidity and bradykinesia with minimal to Metaclopramide Neuroleptics Phenothiazines no tremor Reserpine Butyrophenones SSRI Amiodarone Diltiazem Valproic acid • Dystonic limb posturing early in disease. Lithium • Infectious • Very asymmetric • Postencephalitic, syphlis • Metabolic/Toxic • Minimal to no response to levodopa. • Hypothyroidism, hepatocerebral degeneration, hypoxia, carbon monoxide, carbon disulphide, cyanide, MPTP. Multiple Systems Atrophy Other causes of • MSA –type P (Striatonigral Degeneration): Parkinsonism 9 Akinetic rigid parkinsonism with minimal response to levodopa • Other Hereditary degenerative diseases • MSA – type A (Shy-Drager Syndrome): 9 Huntington’s Disease (juvenille), Wilson’s disease, Neuroacanthocytosis 9 Akinetic rigid parkinsonism with early prominent autonomic dysfunction (papillary changes, postural • Dementia syndromes hypotension, urinary incontinence, cardiac arrhythmia, upper airway obstruction) 9 Significant cognitive issues or dementia prior to or within a year of parkinsonian motor • MSA – type C (Olivopontocerebellar Atrophy): symptoms 9 Parkinsonism with cerbellar ataxia, abn eye movements, retinal degeneration, pyramidal tract • Diffuse Lewy Body Disease dysfunction. May be familial in an autosomal dominant pattern • Alzheimer’s disease 6 Parkinsonian Medications Levodopa • Approved by FDA in 1970 • Parkinsonian medications increase dopamine • Levodopa is the cornerstone of treatment of Parkinson’s activity via precursor levodopa, dopamine Disease motor symptoms, despite all the other available agonists or blockage of enzymatic breakdown medications! (MAO-B inhibitors) • Levodopa provides anti-parkinsonian benefit over the entire course of the
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