Movement Disorders Flashcards
Parkinson’s disease - pathology
*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
lewy bodies
*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
Parkinson’s disease - risk factors
*advanced age
*male gender
*industrial-level exposure to pesticides or herbicides
Parkinson’s disease - genetic mutations
*note: 90% of Parkinson’s disease is sporadic; only about 10% is hereditary
*SNCA mutation
*GBA mutation
*PRKN mutation
*LRRK2 mutation
core motor features of Parkinson’s disease
1. bradykinesia/hypokinesia (decreased speed and amplitude of movements)
2. rigidity (often cogwheel rigidity)
3. resting tremor (not a given in PD; can still have parkinson’s w/o a tremor; usually pretty slow speed)
4. postural instability
5. asymmetry
non-motor features of Parkinson’s disease
*loss of smell (anosmia)
*cognitive changes
*sleep disturbances (REM-behavior disorder; insomnia)
*mood disturbances
*autonomic dysfunction (constipation, orthostatic hypotension, urinary dysfunction)
“red flag” features in Parkinsonism (may indicated atypical parkinsonism)
*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
Multiple Systems Atrophy (MSA)
*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
Dementia with Lewy Bodies (DLB)
*a type of atypical parkinsonism
*synucleinopathy
*signs of dementia within 1 year of parkinsonism onset (psychosis/hallucinations/delusions, fluctuating mental status, autonomic dysfunction)
Progressive Supranuclear Palsy (PSP)
*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
corticobasal degeneration (CBD)
*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)
treatment of parkinsons disease - medication
*dopamine precursor (gets converted into dopamine) - levodopa/carbidopa
*others include dopamine agonists, drugs that reduce the breakdown of dopamine, amantidine, or anticholinergics
treatment of parkinson’s disease - lifestyle changes
*EXERCISE - seems to be neuroprotective and slows disease progression
*physical therapy
*occupational therapy
*speech therapy
advanced Parkinson’s disease
*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)
vascular parkinsonism
*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
drug-induced parkinsonism
*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)
normal pressure hydrocephalus
*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
tardive dyskinesia
*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
neuroleptic malignant syndrome
*rapid onset of hyperthermia, elevated CK, altered mental status, muscle rigidity, and sometimes dystonic postures
*remove offending agents to treat (primarily caused by antipsychotic meds
essential tremor
*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
chorea
*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
Huntington’s disease - inheritance pattern
*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
Huntington’s disease - pathophysiology
*selective degeneration in the striatum (caudate + putamen)
*CAUDATE ATROPHY is a hallmark radiologic finding
Huntington’s disease - clinical presentation
*most common hereditary cause of chorea
*behavioral symptoms (aggression, dementia) and psychosis may precede motor symptoms -> chorea, rigidity, dystonia, dementia
*CAUDATE ATROPHY is a hallmark radiologic finding
dystonia
*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
generalized dystonia
*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)
adult-onset dystonia
*focal dystonia (remains in that one part of the body)
*examples: blepharospasm, cervical dystonia, Writer’s cramp
*treatment = botox injection
basal ganglia affected by: Parkinson’s disease
*substantia nigra (loss of dopaminergic neurons in pars compacta)
basal ganglia affected by: Huntington disease
*striatum (CAUDATE + PUTAMEN)
basal ganglia affected by: hemiballism
*subthalamic nucleus
basal ganglia affected by: Wilson’s disease
*disorder of copper metabolism that leads to accumulation of copper in various tissues
*in basal ganglia, affects the globus pallidus & putamen
*classic PE finding: wing-beating tremor
