movement disorders

Question 1

tremors

Answer 1

-Common movement disorder
-Rhythmic, involuntary, oscillatory movements
-Any body part (hands and head MC)

-2 main categories:
-Resting tremor
-Action tremors

Question 2

resting tremor

Answer 2

-Occurs when relaxed and supported against gravity

-Etiologies:
-Parkinson’s (esp Pill rolling tremor)
-Drug induced Parkinsonism’s (metoclopramide, neuroleptics)
-Supranuclear palsy
-Wilson’s disease

-usually Asymmetric at low frequency with coarse movements
-Improved with target-direct movements
-Worsens with stress
-Clinical diagnosis
-Tx: Dopaminergic agents (carbidopa-levodopa)

Question 3

essential tremor

Answer 3

-MC movement disorder (5% worldwide)
-Autosomal dominant
-Teens and 6th decade of life

-Action! tremor
-Postural, intentional tremor of the hands (90%), forearms, head (30%), neck or voice (15%)
-UE&raquo_space;> LE
-seem with arms against gravity
-Bilateral (symmetric compared to Parkinsons)
-Worse with anxiety/stress/caffeine, intentional or postural movements
-Temporary relief with ETOH!!!

-Exam:
-On finger-to-nose test -> tremor increases as it approaches the target
-No other neuro findings!

-Workup
Electrolytes, TFTs
-No brain imaging required

-Tx not usually required
-Propanolol!!! may help if severe or situational , consider short acting BZD or primidone
-Resistant/treatment failure: gabapentin, topiramate, nimodipine

Question 4

action tremor: intention tremor- etiology

Answer 4

-tremor starts once you get close to target
-Coarse hand tremors
-Zig zag movements that worsen as the body part approaches the target!
-Improved with rest

-Etiology
-Cerebellar lesions! (stroke, tumor, trauma)
-Drug induced: alcohol abuse, lithium
-Multiple sclerosis !
-Wilson’s disease
-Midbrain stroke/trauma

-CT/MRI assess for cerebellar lesions, multiple sclerosis
-Screen for alcohol abuse or lithium toxicity

-Remember the other cerebellar signs:
-Dysmetria (FTN, HTS test)- finger to nose -> over/under shoot
-Dysdiadochokinesia (RAHM test)- rapid alternating
-Dysarthria, nystagmus, abnormal gait

Question 5

action tremor: physiologic tremor

Answer 5

-We ALL have these
-Does NOT dictate an underlying disorder

-Sympathetic stimulation:
-Stress, exercise, fatigue
-Intoxication: caffeine, alcohol
-Drug: valproate, lithium, SSRI, TCAs, B2 agonists, levothyroxine
-Withdrawal: Alcohol, benzodiazepines, barbituates, marijuana
-Medical: Hyperthyroidism, pheochromocytoma
-Other: Hypoglycemia

-Clear history = no diagnostic testing

Question 6

meds that exacerbate tremor

Answer 6

Question 7

movement vocab

Answer 7

Question 8

Hyperkinetic movements

Answer 8

-Tremor
-Rhythmic oscillations usuallybrought onby action
-MC organic and functional movement disorder

-Dystonia
-sustained, Patterned movements
-Sensory trick- do certain things to stop it like touch your face
-May be task-specific- worsens when you try to stop it
-ex. parkinson, huntingtons

-Chorea
-Random movements, parakinesia (attempt to incorporate into their normal movements)
-dance like, rhythmic
-incorporate it into daily movements
-Motor impersistence

-Tics
-paroxysmal
-stereotypes muscle contractions causing movements or vocalizations with premonitory urge
-similar patterns repeat
-temporarily suppressible
-Suggestible = talking about it may trigger it

-Myoclonus
-Lightning-like movements!
-Negative(loss of tone with compensatory contraction ->Asterixis)
-or positive (involuntary contraction)

Question 9

57 year oldmale
PMH: HTN (lisinopril) hypothyroidism (synthroid)
Right arm shaking x 2years
Initially in thumb, nowslowly progressed toentire hand
Mostly at rest, improves with movement
ROS: Mild decrease in smell
Otherwise no other neurologic symptomsincludingchanges in walking orbalance,sleep
Mild rest tremor noted in right hand
Trace rest tremor in left hand
Tremor re-emerges on posture holding
Slight slowness of left finger/toe taps
Decreased left arm swing
Pull test normal

Answer 9

tremors
-bradykinesia
-no arm swing
-pull test normal -> not sever
-parkinsons

Question 10

parkinson’s disease

Answer 10

-Neurogenerative disease of the dopamine! producing neurons
-2nd most common neurodegenerative disease after Alzheimer’s
-Age onset: 45-65 years
-1% of adults > 65 years old
-progressive and chronic with no cure

-Risk factors:
-Genetic: 10-15% are familial
-Diet/metabolism: Low Vit D, high iron, obesity, Wilsons disease (too much copper)
-Hx of TBI

-DoPAmine Down = PArkinsons Dz!

Question 11

parkinson’s disease: etiology

Answer 11

-Normally dopamine inhibits ACH in the substantia nigra of the basal ganglia
-In Parkinson’s, there is damage to the substantia nigra and dopaminergic neurons
-Less dopamine -> more ACH -> uncontrolled movement

-Aggregates of misfolded α-Synuclein and other proteins = Lewy bodies
-motor symptoms first then dementia

Question 12

parkinsonism

Answer 12

-Bradykinesia, resting tremor, rigidity

Question 13

Primary Parkinsonism

Answer 13

-Parkinson’s disease
-Idiopathic dopamine depletion
-Possible genetic factors: α-Synuclein, LRRK2, PARK2 mutations

Question 14

secondary parkinsonisms

Answer 14

-Drug induced = Typical antipsychotics (Haldol), antiemetics (metoclopramide, chlorpromazine), amiodarone, valproate, lithium
-Vascular = ischemic small vessel disease (lacunar) esp of the internal capsule
-Structural brain lesions = hydrocephalus, chronic SDH, tumors
-Recurrent TBI
-Metabolic disorders/toxins = chronic liver failure, rapid sodium shifts, copper or iron deposition diseases in basal ganglia, certain pesticides etc.

Question 15

atypical parkinsonisms

Answer 15

-diagnosed by specialists
-dont need to know these
-Progressive supranuclear palsy (PSP)
-Corticobasal degeneration (CBD)
-Multiple system atrophy (MSA)

Question 16

parkinson’s disease: non-motor symptoms (SOAP)

Answer 16

-!Sleep disturbances
-Insomnia
-REM sleep behavioral disorder
-Restless leg syndrome
-Excessive daytime sleepiness

-Other
-Fatigue
-Seborrheic dermatitis (20-60%)
-Anosmia

-Autonomic symptoms
-Drooling
-!Constipation
-Sexual dysfunction
-Urine problems
-Dysphagia or speech impairment
-Orthostatic hypotension

-Psychologic
-!Anxiety, depression , apathy
-Psychosis (20-40%)
-Dementia develops in 50% of patient (late finding)

Question 17

parkinson’s disease exam: tremor

Answer 17

-Signs of Parkinson’s progress over time
-Unliteral at onset -> progress to bilateral

-Tremor
-Often: resting, distal UE, asymmetric
Observe at rest (resting tremor) “pill-rolling”
-Hold arms out against gravity (postural tremor)
-Finger to nose test (action/kinetic tremor)
-Can involve: jaw, lips, tongue, legs
Micrographia

Question 18

parkinsons disease: rigidity

Answer 18

-!Resistance to passive joint movement independent of speed
-Most sensitive area is the wrist!!!
-Froment maneuver can make it easier to detect subclinical rigidity -> make them do something with one wrist and observe the other

-!Cogwheel rigidity = ratchet pattern of resistance/relaxation while moving the limb through full ROM
-!Lead-pipe rigidity= tonic resistance, smooth through entire passive ROM
-!Stooped posture, decreased arm swing, stiffness and pain
-Masked facies

Question 19

parkinson’s disease exam: akinesia/bradykinesia

Answer 19

-!!Slowness of voluntary movement and decreased automatic movements described as “weakness, incoordination, tiredness”
-Decreased blinking
-Difficulty with rapid finger tapping, or, opening and closing a fist
-Wrist pronation-supination
-Toe or heel taps

Question 20

parkinson’s disease exam: postural instability (coordination and gait)

Answer 20

-progressive
-Imbalance and tendency to fall
-Difficulty getting up from a chair
-!Shuffling gait with short quick steps, decreased arm swing, and freezing
-a lot of trouble turning
-!+Pull test = Unable to stop themselves from going forward (propulsion) or backward (retropulsion)

Question 21

parkinson dx

Answer 21

-Clinical diagnosis
-CT/MRI brain to rule out secondary causes
-DaTSCAN: SPECT scan to evaluate levodopa uptake and conversion to dopamine within the substania nigra

Question 22

early tx of parkinsons disease

Answer 22

-No cure! Goal is to improve symptoms. Does not slow down progression
-pts can refuse until they need tx

-Levodopa (L-Dopa), Levodopa-Carbidopa (Sinemet) * #1 choice
-Precursor to dopamine
-Most effective tx and generally safe BUT is associated with time/dosage dependent dyskinesias
-S/E: !N/V, orthostatic hypotension!, dizziness, somnolence or insomnia, tardive dyskinesia, impulse control, behavioral abnormalities (psychosis!, hallucinations!)
-Cons: Multiple times per day dosing -> need to take it more and more as time goes on
-Do NOT abruptly stop -> Akinetic crisis -> neuroleptic malignant syndrome

-Dopamine receptor agonists: Pramipexole, Ropinirole, Rotigotine
-Less effective than levopdopa, less dyskinesia, once a day dosing
-S/E: More frequent cognitive side effects than levodopa
-If pt is resistant to levodopa, will be resistant to dopamine agonists

-MAO-B inhibiters: Selegiline, Rasagiline, Safinamide
-MAOB normally breaks down dopamine
-block dopamine breakdown
-Poorer efficacy, less side effects, more likely to cause serotonin syndrome (do not coadminister with TCAs, SSRIs)
-Often started first for mild sxs with minimal impact on QOL

Question 23

Patient eventually started on LEVODOPA after discussion on side effects and efficacy

Fast forward 5 years:
States good control until recently
Levodopa only works for ~1 hr
He is slower, stiffer, and occasionally falls when the levodopa wears off
Also new hyperkinetic movements
Difficulty concentrating, multi-asking, and getting words out
Depressed and anxious
Acting out vivid dreams

Is this typical of Parkinsons?

Answer 23

yes
-late stage parkinsons

Question 24

progression of parkinsons

Answer 24

-before dx- sleep problems, constipation, anosmia, depression
-at dx- bradykinesia, rigidity, tremor
-late- falls, dementia, psychosis

Question 25

on-off phenomenon

Answer 25

-Progressive degeneration of nigrostriatal dopamine terminals limits the normal uptake/release of dopamine
-Reduces buffering of natural fluctuations of levodopa due to short half life

-mild stages of parkinsons- a lot of dopamine neurons available -> therapeutic window is larger
-troughs happen when you take levadopa -> peaks throughout day
-on time- when the meds are working
-off time- no levadopa in the system -> symptoms
-as you have less and less neurons as disease progresses -> therapeutic window becomes smaller and smaller -> delayed-on and wears off faster
-too much dopamine for the receptors -> dyskinesia

Question 26

PD-OFF vs PD-ON handwriting

Answer 26

Question 27

late tx of parkinsons disease

Answer 27

-NMDA Antagonist: Amantadine
-Treats mild symptoms of tremor and dyskinesias
-Can worsen confusion, hallucinations, nightmares
-Increased dopamine release, and decreased reuptake

-COMT inhibitors: Entacapone, Opicapone, Tolcapone
-Extend the half life of levodopa by inhibiting the enzyme that breaks down levodopa
-Treats motor fluctuations
-Can worsen some dyskinesias
-Liver toxicity side effect

-Anticholinergics: Benztropine
-Decreases acetylcholine concentration
-!GOOD for monotherapy in young patients whose only symptoms are TREMORS
-Does not affect bradykinesia
-Cognitive side effects are severe (memory impairment), dry mouth, dry eyes, constipation, urinary retention, impaired sweating, tachycardic

-Deep brain stimulation (video to right)
-Implanted leads connect to an impulse generator in the chest under the skin, which stimulates the globus palladus or subthalamic nucleus. Safe, reversible. Cons: hardware can fail, peri-op and post-op complications

Question 28

meds chart

Answer 28

Question 29

drug induced parkinsonisms

Answer 29

-Most important differential when considering Parkinson’s disease
-Drug induced = potentially reversible with cessation of agent
-Clinically indistinguishable from Parkinson’s (except maybe more bilateral?)
-Symptoms/signs can improve in ~80% of pts within 8 weeks of discontinuation of offending agent
-haldols, antiemetics-metoclopramide

Question 30

A 72 year old woman with a history of Parkinson’s controlled with levodopa, presents because of seeing things that she knows are not there. Sometimes she sees a dog in her kitchen, or a stranger in her garden, which no one else sees. She reports quitting drinking alcohol three months ago. Reports no motivation to do daily tasks. Exam shows a mild resting tremor of the hands and bradykinesia. Her thought process is logical. Which of the following is the most likely cause of her symptoms?

Answer 30

A. Schizophrenia
B. Adverse effect of medication!!! -> levadopa can cause hallucinations
C. Alcohol withdrawal
D. Major depressive disorder

Question 31

huntington’s disease

Answer 31

-Inherited, progressive neurodegenerative disorder
-!!Autosomal dominant

-!CAG (cytosine-adenine-guanine) -> more repeats of this -> earlier and worse symptoms
-High dopamine levels
-Causes neurotoxicity, cerebral and caudate nucleus atrophy -> ↓ ACH and GABA

-Male > Female
-Higher prevalence in western European
-Symptom onset ~30-40 years old
-fatal within 15-20y after onset
-5-10% of cases occur as juvenile HD
-becoming earlier and earlier bc more repeats of CAD

-Clinical manifestations:
-1. Psychiatric problems: Marked behavioral, personality, psychiatric changes
-2. Choreiform movements
-3. Dementia

Question 32

huntington manifestations: chorea

Answer 32

-defining feature at dx – face, trunk, limbs
-Chorea (“dance-like gait”) = involuntary, sudden, irregular, non-repetitive, arrhythmic movements of the limbs, neck, head, and/or face
-May be unaware of movements or incorporate into purposeful actions (termed parakinesia)
-Hypotonia with hyperreflexia (early signs) +/- dystonia
-!!Progressive loss of voluntary motor control
-Becomes more florid, widespread, interfering with movement
-Late: affects diaphragm, pharynx, larynx -> dysarthria, dysphagia, involuntary vocalizations
-!!!Motor impersistence: difficulty with sustained tongue protrusion
-CHOREA is common in early stages. Hypokinetic/akinetic symptoms may dominate in late stages.

Question 33

Huntington manifestations: eye movement, cognitive impairments/dementia, wt loss and cachexia

Answer 33

-EYE MOVEMENTS
-Delay in initiation of volitional saccades (quick conjugate eye movements between points of fixation)

-COGNITIVE IMPAIRMENT AND DEMENTIA
-Inevitable cognitive decline (executive function, recall)
-Late: memory loss

-WEIGHT LOSS AND CACHEXIA
-Common features, despite caloric intake
-Unclear pathophysiology - energy expenditure? Altered metabolism?

Question 34

huntingtons manifestations: psychiatric symptoms

Answer 34

-Can occur years prior to onset of chorea
-!!Major depressive disorder
-!!Schizophrenic-like psychosis:
-!Paranoid delusions
-!Auditory hallucinations
-Can occur at any point

-Aggression, apathy, anxiety

Question 35

huntington manifestations: atypical features

Answer 35

-Adults – can present with signs of parkinsonism without tremor
-Juvenile - <20 y/o, can include myoclonus, seizures, behavioral problems,parkinsonism; absent chorea

Question 36

huntington’s disease workup

Answer 36

-Neuroimaging not needed
-MRI/CT reveals !caudate nucleus atrophy!

-Genetic testing: PCR for CAG
->36 repeats is confirmatory
-More repeats = earlier onset
-Indicated in:
-Adults with motor signs suggestive of Huntington’s disease
-Children of HD+ parent with signs of juvenile onset HD

-Not recommended in asymptomatic children/adults

Question 37

huntington disease: treatment

Answer 37

-There is NO CURE, NO SLOWING, NO REVERSING
-Physicians guide to the management of HD
-Goals of care
-Multi-disciplinary approach - Neurologist, psychiatric, psychologist, geneticist, SW, PT, OT, SPT, Hospice

-Chorea sxs:
-!!Tetrabenazine
-2nd gen antipsychotics: olanzapine, risperidone, aripiprazole,
-1st gen antipsychotics: haloperidol, chlorpromazine

Question 38

tetrabenzaine (SKIP)

Answer 38

-Indications: mild, mod, severe chorea, refractory to non-pharm measures
-Dopamine-depleting agents: inhibit pre-synaptic vesicular monoamine transporter type 2 (VMAT2!) -> depletes dopamine release
-Dosing: 12.5 mg daily x 1 week, then 12.5 mg BID, increase by 12.5 mg increments/week until chorea improves or AE occur
-Can be expensive, manufacturer assistance program
-AE: depressed mood (rapid, severe onset), sedation, akathisia, parkinsonism, prolonged QTc
-BB: Increased risk of suicidality
-With SSRIs (CYP 2D6 inhibitor) – reduce dose by 50%

Question 39

38 year old male presents for worsening mood and irritability that first began several months ago. His wife also notes that he has been having “shaky” movements in the limbs and trunk. No past medical history or medication use. Father died of suicide at age 45 years old. He speaks slowly and quietly. Recall is poor at 1/3 words. There are irregular movements of the arms and legs at rest. Muscle strength 5/5, reflexes 2+, sensation intact. Further evaluation might show which of the following?

Answer 39

A. Babinski sign
B. Oligoclonal bands on lumbar puncture -> MS
C. Medial lobe atrophy on MRI -> some Alzheimer’s, seizure types
D. Caudate nuclear atrophy on MRI!!!

Question 40

Restless leg syndrome: AKA Willis-Ekbom Disease (WED)

Answer 40

-!SLEEP related movement disorder
-!Urge to move the legs- Associated with an unpleasant sensation in the legs
-!Worsens with rest (sitting, lying down) thus worse at night! -> Worse w/ antihistamines, DAs, TCAs/SSRIs/SNRIs, Mirtazapine
-!Relieved with movement (walking, stretching, rubbing/pressure)
-if Associated with !involuntary jerking movements! of leg during sleep, known as periodic limb movements of sleep (PLMS)

-Epidemiology:
-5-15% of adults; primarily Caucasian
-FH (+) in 40-60%
-Female > male
-Peak incidence: 30-40 years of age

Question 41

restless leg syndrome primary vs secondary

Answer 41

-Primary RLS: Idiopathic, familial in up to 77% of cases

-Secondary RLS: Underlying condition or drug
-Iron deficiency
-Vitamin deficiency
-Peripheral neuropathy (esp DM)
-Kidney failure (uremia)
-Depression, anxiety
-Inflammatory: Celiac, rheumatoid, IBD
-Neuro: Parkinson’s disease, Multiple sclerosis, Polyneuropathies, spinal cord diseases
-Drugs: H1 antihistamines, antidepressants, dopamine antagonists, lithium, beta blockers
-Pregnancy

-Not attributable to: myalgia, venous stasis, leg edema, arthritis, leg cramps, positional discomfort, habitual foot tapping

Question 42

restless leg syndrome: dx and tx

Answer 42

-Clinical diagnosis
-Check for: CBC/Ferritin (Iron stores), BUN/Cr (Uremia)

-Non pharmacologic therapy:
-Avoid alcohol / caffeine , certain medications (antidepressants, metoclopramide, Benadryl)
-Do mentally alerting activities while at rest
-Regular exercise
-Leg massage, soaking legs in warm bath, pneumatic compression devices.

-Treat underlying cause
-PO iron repletion therapy if serum ferritin ≤ 75 mg/dl

-!Gabapentinoids (Alpha-2-delta calcium channel ligands): Gabapentin, Pregabalin
-Comorbid pain, anxiety, insomnia
-First line for most patients unless contraindicated

-Dopamine Agonists: Pramipexole (Mirapex), Ropinirole (Requip)
-comorbid depression or obesity/metabolic syndrome

-Consequences:
-Sleep onset insomnia, nocturnal awakenings, depression/anxiety

Question 43

tic disorders

Answer 43

-1. tourettes syndrome
-2. persistent motor or vocal tic disorder
-3. provisional tic disorder

-Tics are considered a neuropsychiatric disorder
-!Quick, involuntary, intermittent, non-rhythmic movements or vocalizations
-Happen repetitively
-Not cause by other disorders (substance abuse, HD)
-Premonitory urge: Tics are often preceded by a feeling or urge to tic

-Diagnosed in 1% of children (motor and vocal tics)
-Male&raquo_space; Female
-Associated with: ADHD!, OCD!, learning disabilities, sleep disorders, conduct disorders, mood/anxiety disorders, Family history of tics, or Tourette’s
-Most severe before puberty- Worsens with stress, anxiety, exhaustion
-50% have symptom resolution by age 18

Question 44

vocal and motor tics

Answer 44

-dont memorize all the vocab

Question 45

tourettes syndrome

Answer 45

-Tourette’s must have:
-Onset before 18 (usually between 4-6)
-Tics persist ≥ 1 year
-≥ 2 motor tics
-≥ 1 vocal tic

-NOT explained by other medical conditions or substance use (cocaine)

Question 46

tourette’s syndrome and tic disorders: management

Answer 46

-Management:
-Cognitive behavior intervention for tics (CBIT)
-Habit reversal training (HRT)
-Anxiety and depression reducing strategies

-Medication
-Dopamine blocking agents (Haloperidol, Risperidone. New: Tetrabenazine off-label)
-Side effects: tardive dyskinesia

-Botox injections minimize appearance of tics
-Consider SSRI!! if concomitant OCD
-Consider Alpha-adrenergics (!clonidine, guanfacine!) if concomitant ADHD

-If mild symptoms: watchful waiting

-Most persons have symptom improvement during adolescence
-50% have spontaneous resolution by 18yo

Question 47

dystonias

Answer 47

-slower than tics
-involuntary muscle contractions

Question 48

tardive dyskinesia

Answer 48

-Medication induced movement disorder a/w dopamine blocking agents
-E.g. antipsychotics, metoclopramide, prochlorperazine

-Dystonic (hyperkinetic) movements that persist at least 1 month after discontinuation of causative medications
-Protruding and twisting movements of the tongue
-Pouting, puckering, smacking of the lips
-Blepharospasms
-“piano playing” finger movements
-Shoulder shrugging

-Diagnosis is made by good medication history (at least 1 month of dopamine blocking agent) and exclusion of other abnormal movements

Question 49

extrapyramidal symptoms (EPS_

Answer 49

-EPS = movement disorders due to disruption of dominergic pathways in the basal ganglia causing bradykinesia, rigidity, dystonia, athetosis, chorea, ballismus, akathisia, tics, tremors
-Higher risk with first generation and high dose antipsychotics
-Metoclopramide and some antidepressants can also cause EPS

Question 50

dystonia with meds

Answer 50

-after med reaction:
-hours to days: acute dystonia- toricolis -> oculogyric crisis, tongue protrusion
-give antihistamine, benzos

-days to weeks:
-pseudoparkinsonism
-akathisa- restlessness, cant sit still -> give propanolol

-months to years:
-tardive dyskinesia