Movement Disorders

Question 1

Parkinson’s disease - pathology

Answer 1

*loss of pigmented neurons in the substantia nigra -> decreased dopamine and breakdown of nigrostriatal pathway -> motor symptoms of Parkinson’s disease
*impacts both the direct and indirect pathways, with net effect being LESS CORTICAL ACTIVATION

Question 2

lewy bodies

Answer 2

*cytoplasmic inclusions containing alpha-synuclein
*found in the highest concentration in the substantia nigra, but also in other areas of the nervous system
*characteristic finding of Parkinson’s disease

Question 3

Parkinson’s disease - risk factors

Answer 3

*advanced age
*male gender
*industrial-level exposure to pesticides or herbicides

Question 4

Parkinson’s disease - genetic mutations

Answer 4

*note: 90% of Parkinson’s disease is sporadic; only about 10% is hereditary
*SNCA mutation
*GBA mutation
*PRKN mutation
*LRRK2 mutation

Question 5

core motor features of Parkinson’s disease

Answer 5

*bradykinesia/hypokinesia (decreased speed and amplitude of movements)
*rigidity
*resting tremor (not a given in PD; can still have parkinson’s w/o a tremor; usually pretty slow speed)
*postural instability
*asymmetry

Question 6

non-motor features of Parkinson’s disease

Answer 6

*loss of smell (anosmia)
*cognitive changes
*sleep disturbances (REM-behavior disorder; insomnia)
*mood disturbances
*autonomic dysfunction (constipation, orthostatic hypotension, urinary dysfunction)

Question 7

“red flag” features in Parkinsonism (may indicated atypical parkinsonism)

Answer 7

*symmetry at onset
*early postural instability - PSP, MSA
*early eye movement abnormalities - PSP
*early autonomic dysfunction - MSA
*prominent cerebellar signs - MSA
*early cognitive impairment/hallucinations - DLB
*cortical signs - CBD
*poor response to levodopa

Question 8

Multiple Systems Atrophy (MSA)

Answer 8

*a type of atypical parkinsonism
*synucleinopathy (more in brainstem and ANS)
*early autonomic dysfunction (orthostatic hypotension, urinary retention, impotence, abnormal sweating)
*MSA-C variant with cerebellar features: ataxia, dysrarthria
*MSA-P variant resembles parkinsons

Question 9

Dementia with Lewy Bodies (DLB)

Answer 9

*a type of atypical parkinsonism
*synucleinopathy
*signs of dementia within 1 year of parkinsonism onset (psychosis/hallucinations/delusions, fluctuating mental status, autonomic dysfunction)

Question 10

Progressive Supranuclear Palsy (PSP)

Answer 10

*a type of atypical parkinsonism
*tauopathy (deposition of abnormal tau protein in the brain)
*eye movement abnormalities: initially slow eye movements, then supranuclear vertical gaze palsy
*early postural instability and falls: loss of postural reflexes; backward falls are common

Question 11

corticobasal degeneration (CBD)

Answer 11

*a type of atypical parkinsonism
*tauopathy (deposition of abnormal tau protein in the brain)
*asymmetric parkinsonism (often strikingly so)
*cortical dysfunction (apraxia, sensory loss, myoclonus, alien limb phenomenon)

Question 12

treatment of parkinsons disease - medication

Answer 12

*dopamine precursor - carbidopa/levodopa
*others include dopamine agonists, drugs that reduce the breakdown of dopamine, amantidine, or anticholinergics

Question 13

treatment of parkinson’s disease - lifestyle changes

Answer 13

*EXERCISE - seems to be neuroprotective and slows disease progression
*physical therapy
*occupational therapy
*speech therapy

Question 14

advanced Parkinson’s disease

Answer 14

*patients ultimately develop medication fluctuations, levodopa doses become more frequent over time
*treatment options: deep brain stimulation, carbidopa/levodopa intestinal gel, MRI-guided focused ultrasound (VIM or GPi)

Question 15

vascular parkinsonism

Answer 15

*mimic of parkinson’s disease
*more often from gradual accumulation of subcortical microvascular disease - confluent periventricular/subcortical
*T2/FLAIR hyperintensities
*less often from multiple strokes

Question 16

drug-induced parkinsonism

Answer 16

*mimic of parkinson’s disease
*most closely associated with drugs that antagonize D2 receptors:
-first and second-generation antipsychotics
-antiemetics
-valproic acid, lithium
*REVERSIBLE (but can take months)

Question 17

normal pressure hydrocephalus

Answer 17

*mimic of parkinson’s disease
*dementia, gait disturbance, urinary incontinence (“wet, wacky, and wobbly”) - classic “magnetic” gait
*must have enlarged ventricles out of proportion to brain atrophy

Question 18

tardive dyskinesia

Answer 18

*CHOREA, mostly manifests in face
*likely due to dopamine receptor blockade
*happens with typical and atypical antipsychotics or antiemetics
*may or may not be reversible; can take months to determine

Question 19

neuroleptic malignant syndrome

Answer 19

*rapid onset of hyperthermia, elevated CK, altered mental status, muscle rigidity, and sometimes dystonic postures
*remove offending agents to treat

Question 20

essential tremor

Answer 20

*most common movement disorder
*high frequency tremor, present with posture/action, absent at rest (opposite of parkinson’s tremor)
*usually in upper extremity
*often responsive to alcohol
*top treatments = propranolol + primidone

Question 21

chorea

Answer 21

*wiggling, dancing, writhing, non-stereotypes - with mild chorea patients often just appear fidgety
*pathophysiology involves striatal dysfunction
*caused by a host of neurodegenerative processes: Huntington’s disease, Lupus, Wilson’s disease, etc

Question 22

Huntington’s disease - inheritance pattern

Answer 22

*autosomal dominant
*trinucleotide repeat (CAG) expansion in the HTT gene (encodes huntingtin protein) on short arm of chromosome 4
*expansion more likely when inherited paternally

Question 23

Huntington’s disease - pathophysiology

Answer 23

*selective degeneration in the striatum (caudate + putamen)
*CAUDATE ATROPHY is a hallmark radiologic finding

Question 24

Huntington’s disease - clinical presentation

Answer 24

*most common hereditary cause of chorea
*behavioral symptoms and psychosis may precede motor symptoms -> chorea, rigidity, dystonia, dementia
*CAUDATE ATROPHY is a hallmark radiologic finding

Question 25

dystonia

Answer 25

*stereotyped, spasmodic movements and/or abnormal posturing
*in focal dystonia, patients often have a “sensory trick” to stop the spasmodic movement
*pathophysiology: loss of inhibition, abnormal increased plasticity, abnormal sensorimotor integration

Question 26

generalized dystonia

Answer 26

*typically presents in childhood
*involves many areas of the body (generalized)
*DYT-1 and other genetic dystonias
*dopa-responsive dystonia (child, young adult warrants trial of low-dose carbidopa/levodopa)

Question 27

adult-onset dystonia

Answer 27

*focal dystonia (remains in that one part of the body)
*examples: blepharospasm, cervical dystonia, Writer’s cramp
*treatment = botox injection