Prevalence Parkinson s Disease Mark S. Baron, M.D. Associate Professor of Neurology Movement Disorders Section VCU School of Medicine Common disorder Approaching 1% by 65 yrs of age, 2% by 80 yrs of age Should also be considered in younger patients, > 10% onset before age 40 3:2 ratio men to women 2 Cardinal Features Clinical Characteristics 1. Bradykinesia/ akinesia- both a slowness and paucity of movements 2. Rigidity- appreciated by the patient and on exam 3. Rest tremor- often more of a postural tremor; not always present 4. Gait dysfunction/ imbalance- classically, a slow, shuffling gait; slow to develop, almost never the sole, predominant feature 3 4 Clinical Characteristics 5 Not Just a Movement Disorder Pain Dementia Mood Disturbances Depression, Anxiety Hallucinations- usually due to medications Bowel and bladder control problems Orthostatic hypotension Impotence Insomnia 6 1
Confirmation of PD Dopamine ()-blocking agents, including neuroleptics and metoclopropamide (reglan) must be looked for, but often bring out underlying PD Confirmation, as a rule, requires showing medication responsiveness (>1000 mg L-dopa may be required). In a patient already on medication, may require weaning medications to prove responsiveness. Tremor however, can be resistant to treatment. Confirmation of PD As a rule, if falling from the outset or wheelchair dependent within 5 yrs, NOT PD Imaging is generally not necessary 7 8 Anatomical Pathways PD Models Normal PD Dyskinesias Subthalamus Movement Movement MOVEMENT 9 10 Etiology Genetic Family studies PET study- over 4 yrs, identical twin pairs abnormal PET in 13 of 18 cases, 4 with PD α-synuclein Two extended families, dominant inheritance, α-synuclein protein in synaptic terminals; Fruit fly model- over-expression produces inclusions/ motor deficits Parkin Auto recessive PD, accounts for a high % of young onset PD (<40 yrs old). Parkin protein acts as a scavenger to remove abnormal proteins Etiology Environment Viral Endemic (Awakenings), MPTP, rotenone, proteasome inhibitors Protective? Smoking, Caffeine, Anti-inflammatories 11 12 2
Differential Essential Tremor (ET/FT) Multiple System Atrophy (MSA) Striatal-Nigral Degeneration (SND), Olivo-ponto cerebellar Atrophy (OPCA), Shy-Drager Progressive Supranuclear Palsy (PSP) Vascular Parkinson s (Binzwanger s Dementia) Normal Pressure Hydrocephalus (NPH) Cortico-basal Ganglionic Degeneration (CBGD) Lewy Body Disease (LBD) Drug-induced Parkinson s (neuroleptics, metoclopropamide) Therapeutic Options Medications Physical Therapy Surgery Pallidotomy/ Subthalamotomy Deep Brain Stimulation cell transplantation 13 14 Initiation of Therapy No therapy has been convincingly shown to slow the course of the disease. Dopamine agonist- ropinorole (Requip) or pramipaxole (Mirapex), theoretically preferred as an initial agent, at least in younger, cognitively intact patients. Common side effects include sedation, nausea, orthostatic hypotension, confusion/ hallucinations, pedal edema. Initiation of Therapy Levodopa (precurser of dopamine, trade name Sinemet)- the most effective and best tolerated agent, but may speed up eventual motor fluctuations. Levodopa is necessarily combined with carbidopa, an enzyme inhibitor to prevent peripheral breakdown outside of the CNS. Anticholinergic agents- ex: trihexyphenidyl (Artane), good agents for treating tremor, but do not benefit other cardinal symptoms. The dosing is frequently limited by side effects of confusion. 15 16 Normal Parkinson s Disease Progressing Stages of PD Brainstem Striatum blood vessels Reduced dose effects Progressively increase doses Reduced duration of medication response Progressively increase the frequency of L- dopa CR/SA carbidopa/ levodopa (longer-acting formulations), entacapone (a COMT inhibitor, Stalevo- combination pill) 17 18 3
Advanced Stages of PD Responses are less predictable (sudden offs) Rescue doses of levodopa, apomorphine (Apokyn) Deep Brain Stimulation Surgery Medications produce dyskinesias (involuntary stereotyped movements of the arm/legs/trunk) quetiapine, amantadine Falls are a problem 19 20 MRI-Guided Targeting Microelectrode Target Refinement 21 22 MER Unilateral DBS 23 24 4
Unilateral DBS 25 5