73/74. BG/Movement Disorders

Question 1

What are the direct and indirect pathways in the BG?

Answer 1

Direct: Striatum blocks GPi/SNr blocks thalamus
(DA = D1R = excites Direct = excites thalamus for movement)

Indirect: Striatum blocks GPE blocks STN/GPi/SNr blocks Thalamus
(DA = D2R = inhibits indirect pathway = more inhibition of indirect)

Question 2

What is the difference between hypokinetic and hyperkinetic disorders?

Answer 2

Hypokinetic: paucity of voluntary movement
(less DA = less Direct and more Indirect = movement inhibition)

Hyperkinetic: excess of movements/abnormal involuntary movements
(more DA = more direct and more blocking of indirect = movement overexcitation)

Question 3

What are the main features of Parkinsonism

Answer 3

Bradykinesia: slowness of movement - decreasing in amplitude
\+1/4 of TRAP
Tremor - at rest 
Rigidity
Akinesia - paucity of movement
Postural Gait Instability

Question 4

How are neurodegenerative diseases categorized?

Answer 4

By the proteinopathy

alpha-synuclein: PD, MSA, Lewy Body Dementia

Tauproteinopathy: PSP, Cortical-Basal syndrome

Question 5

Parkinson’s Disease

• clinical features
• pathophysiology
• histo
• etiology
• risk factors
• sx
• dx workup

Answer 5

ASYMMETRIC in onset of (bradykinesia, rigidity, resting tremor) with RESPONSE to LEVODOPA
PP: progressive neurodegenerative disease, loss of pigmented cells in SNc (produces/releases DA)
Histo: Lewy Bodies (pink clumping of alpha-synuclein protein)
E: many causes (genetics (5% +FHx), enviro) cause a-synuclein accumulation = inflammation, ox stress, apoptotic cascades
RF: Older M>F, +FHx, Exposure (well water, pesticides)
Non-motor sx: anxiety, depression, sleep disturbances, constipation, olfactory deficits
DX: clinical Hx, DaTscan (looks at DA transporter uptake - shows if DA cells are present: “comma = healthy”, “period = unhealthy) - not specific to PD

Question 6

Multisystem Atrophy (MSA)

• type of proteinopathy
• CP
• Dx
• Imaging

Answer 6

a-synuclein proteinopathy
Dx: Autonomic failure (urinary/erectile dysfx, orthostatic hypotension), Levodopa-RESISTANT Parkinsonism, Cerebellar Dysfx
-Oligodendroglial cytoplasmic inclusion bodies (NOT lewy bodies)
CP: symmetric in onset, poor response to levodopa
Imaging: “Hot Cross Bun” sign in atrophied pons - loss of pontocerebellar fibers

Question 7

Progressive Supranuclear Palsy

• type of proteinopathy
• CP
• Dx
• Imaging

Answer 7

Tau Proteinopathy
CP: Downward gaze abnormalities, postural instability (falls), symmetric bradykinesia/rigidity, apathy, anxiety, frontal-lobe dementia, poor response to levodopa
Dx: Tau (+) Neurofibrillary Tangles
Imaging: Hummingbird Pons Midsagittal, Mickey Mouse Pons Axial

Question 8

Cortico-basal Syndrome

• type of proteinopathy
• CP
• Imaging

Answer 8

Tau Proteinopathy
CP: Cortical dysfx (dementia, apraxia, alien limb, visual neglect), Extrapyramidal dysfx (asymmetric parkinsonism, action tremor, focal limb dystonia, myoclonus)
Imaging: Cortical degeneration

Question 9

Dementia with Lewy Bodies

• type of proteinopathy
• CP

Answer 9

a-synucleinopathy
CP: TRIAD of visual hallucinations, fluctuating cognition (<12mo. of parkinsonism), parkinsonism

Note: in PD, Parkinsonism appears first and dementia is very late finding (>12mo)

Question 10

PD Tx

What happens as PD advances?

Answer 10

Tremors only - Anticholinergics
Mild PD = MAO-B inhibitors (prolong DA effects)

Amantadine (NMDA antagonist) - reduce excessive movement, and DA reuptake inhibitor

Levadopa (SE: motor fidgety dyskinesias) > DA agonists (SE: nausea, hypotension, confusion)

Overtime: therapeutic window narrows - levadopa wears off faster and creates more fidgety dyskinesia

Surgical Tx: Deep Brain Stimulation (less SE and need for meds, but does not halt progression of disease)

Question 11

Tremor

• what is it
• classification
• disease and tx

Answer 11

involuntary, RHYTHMIC/oscillatory movement about a joint
Classification: Resting (Parkinsonism), Action (Postural v. Kinetic), Miscellaneous

Benign Essential Tremor: most common; kinetic action tremor during use, 95% UE, tx: propanolol, gabapentin, lesional procedures - thalamotomy

Question 12

Chorea

• what is it
• disease assoc.
• tx

Answer 12

Excessive spontaneous movement from a flow of “dance-like” muscle contractions - irregular, unpredictable, abrupt

Huntington’s Disease: hereditary AD (trinucleotide expansion repeat), causes chorea, inappropriate behavior, dementia, brain/caudate atrophy

Tx: Neuroleptics (antipsychotics, DA receptor blockers)
VMAT-i’s - DA depleting agents in presynaptic DA neurons

Question 13

Dystonia

• what is it
• what is Geste Antagoniste
• disease assoc
• tx

Answer 13

• sustained (not fixed) contraction causing twisting/repetitive movements and abnormal posture, brought on by action, task specific
• GA: sensory innervation (touch) helps relieve abnormal contraction
• assoc: TORTICOLLIS - neck dystonia (or WRITER’S CRAMP)
• tx: Generalized (Anticholinergics, GABA-ergics, DA Antagonists), Focal (BOTOX), Surgery (DBS)

Question 14

Tics

• what is it
• onset
• comorbidities
• tx

Answer 14

sudden, brief, intermettent movements/utterances that are briefly suppressible, with urged buildup until movement
onset: childhood and adolescence (decline in young adulthood)
co-mo: OCD, ADHD, Depression/Anxiety
Tx: counseling, psychotherapy (alpha agonists, DA antagonists, SSRIs, BOTOX)

Question 15

Myoclonus

• what is it
• what is Asterixis

Answer 15

Brief, lightning-like muscle jerks (SUDDEN)

Asterixis - negative myoclonus (hand flapping)