Parkinsons Flashcards

Question

Criteria for "definite" multiple systems atrophy diagnosis

Answer 1

Findings of widespread and abundant CNS α-synuclein – positive glial cytoplasmic inclusions (Pap–p–Lantos inclusions) Neurodegenerative changes in striatonigral or olivopontocerebellar structures

Answer 2

1. a typical neuropathological lesion pattern: pons, medulla, putamen, cerebellum, SNpc, preganglionic autonomic structures deposition of α-synuclein-positive glial cytoplasmic inclusions 2. MSA: ??? 1° oligodendrogliopathy early myelin dysfunction progressive synucleinopathy associated axonal damage → 2° neurodegeneration

Answer 3

Autonomic failure involving urinary incontinence (inability to control the release of urine from the bladder, with erectile dysfunction in males) or an orthostatic decrease of blood pressure within 3 min of standing by at least 30 mm Hg systolic or 15 mm Hg diastolic and Poorly levodopa-responsive parkinsonism (bradykinesia with rigidity, tremor, or postural instability) or A cerebellar syndrome (gait ataxia with cerebellar dysarthria, limb ataxia, or cerebellar oculomotor dysfunction)

Answer 4

Babinski sign with hyperreflexia Stridor Rapidly progressive parkinsonism Poor response to levodopa Postural instability within 3 yrs of motor onset Gait ataxia, cerebellar dysarthria, limb ataxia, or cerebellar oculomotor dysfunction Dysphagia within 5 yrs of motor onset Atrophy on MRI of putamen, middle cerebellar peduncle, pons, or cerebellum Hypometabolism on FDG-PET in putamen, brainstem, or cerebellum

Answer 5

Babinski sign with hyperreflexia Stridor Parkinsonism (bradykinesia and rigidity) Atrophy on MRI of putamen, middle cerebellar peduncle, or pons Hypometabolism on FDG-PET in putamen Presynaptic nigrostriatal dopaminergic denervation on SPECT or PET

Answer 6

Atypical spontaneous or L-DOPA induced dystonia predominantly affecting orofacial muscles, occasionally resembling risus sardonicus of cephalic tetanus.

Answer 7

Subacute axial dystonia with a severe tonic lateral flexion of the trunk, head, and neck (contracted and hypertrophic paravertebral muscles may be present).

Answer 8

Chin-on-chest, neck can only with difficulty be passively and forcibly extended to its normal position. Despite severe chronic neck flexion, flexion elsewhere is minor.

Answer 9

Atypical quivering, irregular, severely hypophonic or slurring high-pitched dysarthria, which tends to develop earlier, be more severe and be associated with more marked dysphagia compared to PD.

Answer 10

``` Classic pill-rolling rest tremor Clinically significant neuropathy Hallucinations not induced by drugs Onset after age 75 y Family history of ataxia or parkinsonism Dementia (on DSM-IV) White matter lesions suggesting multiple sclerosis ```

Answer 11

``` Orofacial dystonia Disproportionate antecollis Camptocormia (severe anterior flexion of the spine) and/ or Pisa syndrome (severe lateral flexion of the spine) Contractures of hands or feet Inspiratory sighs Severe dysphonia Severe dysarthria New or increased snoring Cold hands and feet Pathologic laughter or crying Jerky, myoclonic postural/action tremor ```

Answer 12

A Hyperintense putaminal rim on T2-weighted images (“Hot cross bun” sign) B Signal change in the pons on T2-weighted images (Pontine atrophy)

Answer 13

1Parkinson’s disease 2Dementia with Lewy Bodies (DLB) 3Multiple System Atrophy (MSA) MSA – P: Parkinson predominant (strionigral degeneration) MSA – C: Cerebellar predominant (Olivopontocerebellar degeneration) 4Pure Autonomic Failure

Answer 14

1. Insidious onset and progressive course 2. No identifiable cause (e.g., tumor or infarction) 3. Cortical dysfunction as reflected by at least one of the following: - Focal/asymmetric ideomotor apraxia - Constructional apraxia - Alien limb phenomenon - Focal or asymmetric myoclonus - Cortical sensory loss – Apraxia of speech/nonfluent aphasia -Visual or sensory hemi-neglect 4. Extrapyramidal dysfunction - Focal or asymmetric appendicular rigidity lacking prominent and sustained levodopa response - Focal or asymmetric appendicular dystonia

Answer 15

Focal/asymmetric ideomotor apraxia – Constructional apraxia Alien limb phenomenon – Focal or asymmetric myoclonus Cortical sensory loss – Apraxia of speech/nonfluent aphasia Visual or sensory hemi-neglect

Answer 16

Symptoms: Limb stiffness Clenched hand ``` Signs: Bradykinesia Dystonia Fisted hand Postural instability Limb tremor ```

Answer 17

1. Asymmetric frontoparietal cortical atrophy | 2. Asymmetric atrophy of the cerebral peduncles

Answer 18

Gradually progressive ≥ age 40 at onset No evidence for competing diagnostic illness Vertical gaze palsy or slowing of vertical saccades + postural instability/falls in 1st year

Answer 19

Progressive intellectual and functional deterioration. Average survival after the time of diagnosis is about 5 years ~ 30% ten-year survival rate

Answer 20

1 Deposits of hyperphosphorylated MAPτ 2 Human CNS τ - Exists as 6 isoforms; three contain 3 microtubule binding repeats (3R), 4 contain a 4th (4R). - ↑ Presence of 4R τ isoforms in PSP 3PSP vs. AD - PSP τ: present as straight filaments within globose PSP tangles in neurons and glia (tufted astrocytes) - AD τ: paired helical filaments in neurofibrillary tangles 4Glial cell pathology rarely seen in other tauopathies

Answer 21

penguin sign: marked atrophy of midbrain tegmentum. The shapes of midbrain tegmentum (bird’s head) and pons (bird’s body) on midsagittal MR images look like a lateral view of a standing penguin with a small head and big body Recall: Patient with MSA-P → marked atrophy of pons.

Answer 22

1 Alzheimer’s Disease 2 Frontotemporal dementias (Pick’s Disease) 3 Tauopathies with predominant Parkinsonism - Corticobasilar degeneration - Progressive Supranuclear Palsy (6/105) - Frontotemporal dementia and parkinsonism linked to Chr 17 (MAPτ mutation with neuronal τ inclusions); but also Chr 17 progranulin mutation with ubiquitin (+ TDP-43) inclusions.

Answer 23

L-Dopa/Carbi-Dopa Dopaminergic agonists Cholinergic antagonists Metabolic inhibitors

Answer 24

(Thalamotomy) (Pallidotomy) Brain stimulation (DBS) In vivo gene therapy

Answer 25

``` Caffeine Coenzyme Q10 Creatine Estrogen GM-1 ganglioside Minocycline Nicotine GPI-1485 Rasagiline Selegiline Ropinirole Pramipexole ```

Answer 26

Bromocriptine Rotigotine Pramipexole Ropinerole

Answer 27

Directly stimulate dopamine receptors Independent of dopamine production No free radical generation Monotherapy or adjunctive therapy

Answer 28

``` Nausea Vomiting Postural hypotension Hallucinations Somnolence Impulse Control Hypersexuality Gambling Spending/shopping ```

Answer 29

Works for almost all patients with Parkinson’s Disease Improvement of disability and possibly mortality Most effect on bradykinesia and rigidity, less effect on tremor and postural instability

Answer 30

Combined in fixed ratios with levodopa Prevents the peripheral conversion of levodopa Total of 75 mg/day is usually required to inhibit peripheral decarboxylase activity

Answer 31

1 high-protein diets cause decreased absorption 2 fluctuation of amount of DA at the receptor sites 3 IR half-life 60-90 minutes

Answer 32

``` nausea/vomiting orthostatic hypotension hallucinations cardiac arrhythmias confusion agitation ```

Answer 33

as dopamine neurons decrease, the medication is less effective. At this point, the effec lasts a couple of hours. Calls for PEG-J tube continuous administration

Answer 34

Refers to the switch in parkinsons disease between mobility and immobility in levodopa treated patients, which occurs as an end-of-dose or "wearing off" worsening of motor function or, much less commonly, as sudden and unpredictible fluctuations. Motor complications occur in 50% of PD patients who have received Levodopa for 5-10 years and constitute a major cause of disability in advanced PD.

Answer 35

``` Fewer daily doses Less plasma fluctuations Delay to effect Cannot crush; can divide No measurable effect on “freezing” ```

Answer 36

Prevents breakdown of dopamine More levodopa available to cross blood brain barrier

Answer 37

1. Tolcapone - severely restricted due to hepatotoxicity - must sign consent form - mainly peripheral, slight central effect 2. Entacapone - increased AUC, increased t1/2; no change in Cmax, or tmax of levodopa - Dosing - One tablet with each levodopa/carbidopa dose; max 8/day - Does not cross blood brain barrier - Must use with levodopa/carbidopa

Answer 38

``` Dyskinesias Nausea Hallucinations/vivid dreams Diarrhea Urine discoloration - orange ```

Answer 39

``` Mechanism of Action - Enhances dopamine release - Blocks reuptake - Stimulates DA receptors - Blocks Glu receptors Dosing - 100 mg 1 po bid-tid - caution in renal dysfunction ```

Answer 40

Treatment of early Parkinson’s disease Treatment of levodopa-induced dyskinesias

Answer 41

``` dizziness nausea nightmares insomnia anxiety livedo reticularis - skin rash ```

Answer 42

1. Trihexyphenidyl, Benztropine 2. Most useful for tremor 3 Best when used with younger patients Avoid in demented patients

Answer 43

Early Parkinson’s disease with tremor as main symptom Later Parkinson’s disease with all symptoms except tremor under good control

Answer 44

``` Initial dosing trihexyphenidyl 0.5 mg 1 po bid benztropine 0.5 mg 1 po bid Adverse effects dry month urinary retention dry eyes constipation confusion ```

Answer 45

four leads on probe, can program them to create different fields. Most commonly placed in GBI. Thalamus: essential tremor

Answer 46

1 Vim Thalamic stimulation will only treat tremor (PD or ET) Utilize this placement if the patient has disabling tremor and milder bradykinesia or rigidity 2 STN Will treat all of the motor symptoms of PD More difficult to program 3 GPI Will treat all of the motor symptoms of PD Location of choice to treat dystonia

Answer 47

1 Peripheral Nervous System → Pain, constipation 2 Spinal Cord → Orthostatic hypotension, urological disturbances 3 Brainstem → Anxiety, depression, sleep disorders Basal Ganglia → Impulse control disorders, apathy, restlessness Cortical → Cognitive, psychiatric disorders, anosmia

Answer 48

shoulder pain is an early and sometimes initial symptom dystonic and cramping pain not uncommon in PD patients, most common in lower extremity Early AM dystonia → dopamine deficit dystonia/dyskinesia → late effect of PD + levodopa tx dystonia → potential side effect of STN DBS programm

Answer 49

1. nausea often associated with initiation of levodopa and peripheral metabolism to dopamine prolonged transit time, constipation, paralytic ileus may result from loss of vagal neurons, changes in myenteric plexus. 2. adequate hydration, high fiber, PEG. psyllium, bisacodyl lubiprostone (intestinal ClC-2 activator; ↑ intestinal fluid secretion) linaclotide (14 aa guanylate cyclase-C agonist → ↑cGMP → increased secretion of Cl- and HCO3- into the intestinal lumen) Both FDA-approved for Irritable Bowel Synd, chronic constipation

Answer 50

``` related to disease & medication 1. treat with ↑fluids, salt 2midodrine ≤ 10 mg tid t ½ of active metabolite = 3-4h 3 fludricortison (≤ 0.1 mg q day) 4 L-DOPS /droxidopa (initial dose: 100mg tid) ``` L-threo-dihydroxyphenylserine → norepinephrine FDA-approved 18 Feb 2014 for PD, MSA, pure autonomic failure, DBH deficiency

Answer 51

``` nocturia most common complaint (>60%) storage symptoms in 57 – 83% voiding symptoms in 17 – 27% urgency 33 – 54%, frequency 16 – 36%. neurogenic detrussor overactivity in 45 – 93% of patients nocturnal polyuria remember: Multiple Systems Atrophy ```

Answer 52

treat if UTI storage symptoms may respond to anticholinergics (oxybutynin, tolterodine, trospium) voiding symptoms may be caused by anticholinergics, bladder outflow obstruction (CMG) (try α-blocker [terazosin, doxazosin, tamsulosin, and alfuzosin] and/or 5-α-reductase inhibitors [dutasteride, finasteride]; intermittent self-catheterization)

Answer 53

Prevalence of depression in PD ~ 40% published rates vary from 7 to 76% ~17% of PD patients may suffer major depressive disorder The major contributors depletion of brain catecholamines and serotonin dysregulation of fronto-subcortical connections that regulate mood Treatment: tricyclics, SSRIs, SNRIs

Answer 54

Nighttime awakenings: < total sleep time, < sleep efficiency, > frequent awakenings dopaminergic treatment strongest predictor Excessive daytime sleepiness (EDS) associated with PD neuropathology & anti-PD medications “sleep attacks” initially described with DAs; similar with all dopaminergic therapies Modafinil (200-400mg/day) may be effective; not FDA approved

Answer 55

REM Behavior Disorder (RBD) people with RBD appear to act out their dreams when in REM sleep ~ 34% of those with probable RBD developed MCI or PD ≤ 4 yrs of entering a Mayo Clinic study (2.2X those with normal REM sleep) RBD affects 30-90% of patients with synucleopathies a non-dopaminergic lesion of the system controlling REM sleep atonia has been implicated (subceruleus-ceruleus complex ?) no randomized, double-blind, placebo controlled study has been reported for RBD; clonazepam (0.5-2 mg HS) appears effective, well tolerated .

Answer 56

Hypersexuality, pathological gambling, compulsive shopping, binge eating Punding: compulsion to perform repetitive mechanical tasks, such as sorting, collecting, or assembling and disassembling common items Addictive behaviors: excessive use/abuse of anti-PD meds Associated with increasing dopaminergic therapy but > 15% of ~100 newly diagnosed PD patients screened + for ≥ 1 ICD

Answer 57

Reduction or withdrawal of dopaminergic therapy, particularly DAs: (pramipexole, rotigotine, ropinirole) ± DBS surgery as means to reduce dopaminergic therapy Other suggestions: SSRIs, quetiapine, valproate, naltrexone, topirimate, donepezil, clozapine

Answer 58

> 80% dementia in end-stage PD Executive dysfunction and visual-spatial problems affects information processing distractablity, passivity, slow-thinking Similar findings in Lewy body dementia (LBD) Cholinergic neuronal loss, ChAT depletion early in PDD/LBD Treatment: cholinesterase inhibitors (rivastigmine, donepezil) NMDA receptor antagonists (memantine)

Answer 59

Prevalence up to 60%; associated with poorer prognosis Hallucinations usually visual; typically begins ~ 10 yrs after dx with retained insight Hallucinations > 2 yrs strong predictor of dementia, NH placement, death. Delusions may occur in younger patients Treatment with quetiapine, clozapine

Answer 60

Associated illnesses, medications, motor symptoms, depression, anxiety and worsening PD contribute Erectile dysfunction in 54 – 79% of men sildenafil 50 – 100 mg in PD patients Women report difficulties with arousal (~88%), reaching orgasm (~75%) A true increase in libido may occur as an adverse reaction to treatment with DAs, levodopa

Answer 61

1. Impaired visual function Visual acuity, contrast sensitivity (disease severity: UPDRS III) Color/motion perception Visualspatial deficit ? Retinal dopamine loss 2. Visual Hallucinations illusions (~25%) feelings of presence and passage (? Correlates with RBD, EDS) complex visual hallucinations (~40%, > association with PDD) 3. Diplopia and difficulty reading disease severity → motility abnormalities, surface irritation excessive daytime somnolence (EDS) 4. Impairments of ocular and eyelid motility abnormal saccades reduced spontaneous blink blepharospasm (advanced PD) apraxia of eyelid opening (advanced PD) 6. Ocular surface irritation dry eyes (up to 2/3 of patients) blepharitis (up to 75%; PD + age)