Movement Disorders

Question 1

Movement Disorders

Overview

Answer 1

Neurologic diseases affecting voluntary control of movement or result in involuntary movements

Movement disorders divided into two categories:

• Hypokinetic diseases
  
  • Parkinson’s Syndrome
  • Lewy Body Dementia
  • Progressive Supranuclear Palsy
  • Corticobasal degeneration
  • Secondary Parkinsonism
    
    • Drug-induced
    • Vascular
    • Post-traumatic
    • Post-infectious
• Hyperkinetic movements
  
  • Essential tremor
  • Huntington’s Disease
  • Dystonia
  • Tics
  • Ataxia
  • Tardive Dyskinesia
  • Psychogenic Movement Disorders

Question 2

Hyperkinetic Movements

Answer 2

• Tremor - Regular oscillations of a body part produced by alternating contractions of reciprocally innervated muscles
  
  • Can be at rest, w/ holding a posture, or w/ action
• Myoclonus - Sudden “lightning-like” movements w/ irregular pauses between jerks
• Dystonia - Sustained muscle contractions resulting in abnormal fixed posture or repetitive involuntary movement
• Athetosis - Writhing movements due to continuous movement of adjacent muscle groups
• Chorea - An excess of rapid, arrhythmic, unpredictable movements, “dance-like”
• Ballism – Large amplitude, proximal, jerking or flinging movements
• Tics - Repeated, individually recognizable, intermittent movements or movement fragments that are briefly suppressible and are usually associated w/ awareness of an urge to perform the movement
• Akasthisia – sense of inner restlessness that often leads to voluntary movement

Question 3

Hypokinetic Movements

Answer 3

• Parkinsonism – a constellation of sx w/ multiple causes (one of which is Parkinson’s disease)
• Freezing of gait
• Psychomotor slowing

Question 4

Parkinsonism

Answer 4

A constellation of sx:

• Bradykinesia – slowness of movement
• Akinesia – difficulty initiating movement
• Rigidity
• Shuffling gait
• +/- tremor (mainly at REST)
• Masked facies – decreased facial expression
• Hypophonia – soft voice

Idiopathic Parkinson’s Disease is one cause of Parkinsonism

Question 5

Motor Control

Answer 5

Corticospinal tract and premotor areas ⇒ motor strength

Basal ganglia and cerebellum ⇒ other aspects of motor control

Question 6

Basal Ganglia

Components

Answer 6

• Deep brain structures that facilitate or inhibit movement:
  
  • Caudate
  • Putamen
  • Globus pallidus – interna and externa
  • Substantia nigra – pars compacta and pars reticulata
  • Subthalamic nucleus (STN)
  • (Amygdala, nucleus accumbens, claustrum)
• Other terminologies:
  
  • Lentiform (lenticular) nucleus = globus pallidus + putamen
  • Striatum = caudate + putamen

Question 7

Basal Ganglia

Function

Answer 7

Controls the contralateral side of the body

Largely facilitates or inhibits movement

Question 8

Basal Ganglia

Neurotransmitters

Answer 8

GABA (⊖) ⇒ striatum, globus pallidus

Glutamate (⊕) ⇒ subthalamic nucleus

Dopamine (⊕ or ⊖) ⇒ SN pars compacta

Question 9

Basal Ganglia

Circuitry

Answer 9

• Inputs to the basal ganglia: Cortex, substantia nigra pars compacta
• Outputs from the basal ganglia: globus pallidus internal segment and substantia nigra pars reticulata
• Mainly project to the thalamus → cortex ⇒ either stimulation or inhibition of movement
• Two pathways are involved: direct pathway and indirect pathway ⇒ opposite effects on movement
• Dopamine stimulates these pathways in different ways to facilitate movement

Question 10

Basal Ganglia

Direct Pathway

Answer 10

Facilitates Movement

• Inhibits output from basal ganglia
• Increases likelihood of movement
• Dopamine acting on D1 receptors is excitatory and stimulates this pathway

Question 11

Basal Ganglia

Indirect Pathway

Answer 11

Inhibits Movement

• Increases output from basal ganglia
• Decreases likelihood of movement
• Dopamine acting on D2 receptors is inhibitory on this pathway, thereby allowing movement

Question 12

Parkinson’s Disease

Overview

Answer 12

Neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra.

• 2^nd most common neurodegenerative disorder behind Alzheimer’s Disease
• Up to 10% of cases have a specific gene mutation
• Onset at age 50 or older but younger cases are seen

Question 13

Parkinson’s Disease

Clinical Manifestations

Answer 13

• Cardinal Features of PD: TRAP mnemonic
  
  • T: tremor – typically a resting tremor
  • R: rigidity
  • A: akinesia or bradykinesia
  • P: postural instability
  • Masked facies, hypophonia, micrographia
  • Symptoms are typically asymmetric
• Non-motor features of PD
  
  • Depression/Apathy
  • Constipation
  • Sexual dysfunction
  • Urinary dysfunction
  • Orthostatic hypotension
  • Cognitive decline – typically late in the course

Question 14

Parkinson’s Disease

Treatment

Answer 14

• Mainstay of pharmacologic treatment is levodopa
• Exercise – Studies show a possible disease modifying effect
• Physical, occupational, and speech therapy – Programs specifically designed for Parkinsonism
• Deep Brain Stimulation
  
  • Adjustable stimulation that modulates basal ganglia circuitry
  • Improves levodopa-responsive symptoms, tremor, bradykinesia, dystonia, increases ON time, reduces dyskinesia
  • Contraindications include atypical parkinsonism, dementia, uncontrolled psychiatric disease, high surgical risk due to other medical conditions

Question 15

Atypical Parkinsonian Syndromes

Answer 15

Neurodegenerative diseases with parkinsonism as a clinical feature.

Both synucleinopathies and tauopathies can have features of Parkinsonism.

• α-synucleinopathies often have REM sleep behavior disorder as a prodrome
• All forms of atypical parkinsonism warrant a levodopa trial, up to high doses if tolerated
• Otherwise, symptomatic treatment is utilized
  
  • PT/OT, botulinum toxin for dystonia, anti-depressants, tx for orthostatic hypotension
• DBS is not efficacious

Question 16

Lewy Body Dementia

Answer 16

• 2^nd most common form of neurodegenerative dementia
• An α-synucleinopathy
• Clinical features:
  
  • Parkinsonism starts w/ or follows dementia onset
  • Fluctuating cognition
  • Recurrent visual hallucinations – typically complex
• Treatment: balance between levodopa for parkinsonism, and treating psychosis

Question 17

Multiple System Atrophy

Answer 17

• An α-synucleinopathy
• Clinical features:
  
  • Parkinsonism – Poorly responsive to levodopa, more symmetric, faster progression
  • Autonomic failure – Orthostatic hypotension, erectile dysfunction, urinary difficulty
  • Cerebellar dysfunction
  • Relative preservation of cognition
  • Anterocollis – patterned, repetitive muscle contractions that result in neck flexion
• Subtypes:
  
  • MSA-P (Striatonigral degeneration) – mostly parkinsonism
  • MSA-C (Olivopontocerebellar atrophy) – mostly ataxia
  • MSA-A (Shy-Drager, no longer considered a distinct subtype) – mostly autonomic failure

Question 18

Progressive Supranuclear Palsy

Answer 18

Tauopathy

Clinical features:

• Early falls – often due to retropulsion and postural instability
• Parkinsonism that is poorly responsive to levodopa, more rapid progression
• Ophthalmoplegia, or impaired vertical eye movements
  
  • Square wave jerks
  • Loss of downgaze is fairly specific
  • Can involve horizontal eye movements over time
• “Stare” – wide stare, procerus activation
• Dementia

Question 19

Corticobasal Degeneration

Answer 19

Tauopathy

• Parkinsonism w/ poor response to levodopa (sometimes markedly asymmetric)
• Alien limb phenomenon – arm or leg assumes postures without the patient’s voluntary control
• Cortical sensory deficits
  
  • Graphesthesia – unable to identify numbers drawn on the hand
  • Loss of stereognosis – unable to identify objects by feel
• Significant dystonia, spasticity, rigidity (often unilateral)
• Cortical myoclonus, apraxia
• Dementia later in the course of disease

Question 20

Secondary Parkinsonism

Answer 20

• Drug-induced parkinsonism
  
  • Most common extra-pyramidal syndrome
  • Often caused by dopamine-blocking drugs
    
    • Including some antipsychotics and antiemetics
  • Can take months to a year to resolve after stopping the offending medication
• Other secondary causes include:
  
  • Vascular parkinsonism
  • Post-encephalitic parkinsonism
  • Post-traumatic parkinsonism

Question 21

DATscan

Answer 21

• Uses ioflupane iodine-123 injection w/ SPECT to image presynaptic dopamine transporters in the striatum
• Does not differentiate between PD, MSA, PSP
• Useful in differentiating essential tremor from PD/MSA/PSP
• Also helpful in differentiating drug-induced parkinsonism from PD
• Is not needed to confirm diagnosis, but can provide info if dx is not clear

Question 22

Hypokinetic Conditions

Comparison

Answer 22

• Parkinson’s Syndrome: tremor, asymmetry, slower progression
• Lewy Body Dementia: early dementia, visual hallucinations
• Multiple System Atrophy: associated autonomic sx; parkinsonism type, cerebellar type
• Progressive Supranuclear Palsy: early falls, opthalmoplegia
• Corticobasal degeneration: unilateral dystonia, alien hand, apraxia
• Secondary Parkinsonism
  
  • Drug-induced (Dopamine blockade)
  • Vascular
  • Post-traumatic
  • Post-infectious

Question 23

Essential Tremor

Overview

Answer 23

Very common cause of tremor

Clinical features:

• Tremor that slowly worsens over years
• Tremor is worst w/ posture and action (unlike rest tremor of Parkinson’s disease)
• Affects arms/hands first, but can also affect head, jaw, voice, legs trunk
• Bilateral, usually roughly symmetric
• Can become disabling in severe cases
• Fhx in ~60%
• Often improves acutely w/ alcohol

Question 24

Essential Tremor

Treatment

Answer 24

• Propranolol (β-blocker) ⇒ first-line therapy
• Primidone (older anti-epileptic med) is another option
• There are other second line treatments which are less likely to be effective
• Deep brain stimulation can be considered if medication fails ⇒ target is typically the VM nucleus of the thalamus

Question 25

Huntington’s Disease

Overview

Answer 25

• Autosomal dominant CAG repeat disease on chromosome 4 affecting the Huntingtin gene
• Onset typically in adulthood
• Duration 5-20 years
• Triad of clinical signs: chorea, cognitive deficits, psychiatric disease
  
  • In later stages, can develop into bradykinesia/rigidity
  • Higher rates of suicide in this population

Question 26

Huntington’s Disease

Treatment

Answer 26

• Treatment is symptomatic
• Tetrabenazine is FDA approved ⇒ ⊗ reuptake and depletes storage of dopamine and other monoamines
• Other dopamine-blocking medications such as haloperidol, risperidone have been used

Question 27

Dystonia

Answer 27

Sustained or intermittent muscle contractions causing abnormal (often repetitive) movements, postures, or both.

• Causes:
  
  • Idiopathic (most cases)
  • Medication-induced (dopamine blockade)
  • Genetic causes
  • Structural – Trauma, stroke
• Can affect one part of the body, multiple parts of the body, or can be generalized to affect the whole body
  
  • Focal – Cervical dystonia (affects neck, most common form), blepharospasm, spasmodic dysphonia
  • Task-specific – embouchure dystonia in musician’s, writer’s cramp, “yips” in golfers
  • Segmental – Meige syndrome
  • Generalized – many of the genetic dystonias such as DYT-1, dopa-responsive dystonia, or secondary dystonias in conditions like Lesch-Nyhan syndrome
• Can be associated w/ geste antagoniste (sensory trick which temporarily relieves the dystonia)
• Treatment includes botulinum toxin for more focal dystonias

Question 28

Tics

Answer 28

Semi-voluntary (e.g. suppressible), repetitive, rapid, non-rhythmic movements or sounds.

• Sensory component – urge to perform the movement
• Associated compulsions
• May be associated w/ OCD, ADHD
• Occasionally tics are disabling

Question 29

Tourette Syndrome

Answer 29

A syndrome consisting of both motor and vocal tics, beginning in childhood and lasting over a year.

Question 30

Tics

Treatment

Answer 30

• Alpha-agonists such as clonidine
• Anti-psychotics such as haloperidol
• DBS in severe cases – also option for treatment of refractory OCD

Question 31

Ataxia

Overview

Answer 31

• Physical finding, not a disease
• Results from damage to cerebellum or cerebellar pathways
• Features:
  
  • Dysmetria – poor targeting of planned movements
  • Dysdiadokinesia – poor sequencing of planned movements
  • Intention tremor – typically coarse, worse closer to the intended target
  • Gait abnormalities – wide based gait w/ poor balance “Drunken sailor’s walk”
  • Eye movement abnormalities

Question 32

Ataxia

Etiologies

Answer 32

• Lesion in the following areas of the brain (caused by strokes, demyelination, brain tumors, etc.):
  
  • Cerebellum
  • Pons
  • Midbrain (Red Nucleus)
  • Olivary Nucleus
  • Thalamus (Cerebellar Inflow Nucleus)
• Acute intoxication
  
  • Alcohol, phenytoin, others
• Chronic substance abuse
  
  • Including alcohol which causes cerebellar degeneration
• Genetic Ataxias
  
  • Autosomal Dominant Ataxias (Spinocerebellar ataxias)
  • Autosomal Recessive Ataxias (e.g. Friedreich’s ataxia)
• Metabolic
  
  • Vitamin E deficiency, Thiamine deficiency, hypothyroidism
• Autoimmune/paraneoplastic
  
  • Gluten ataxia
  • Anti-YO, HU, TR
• Multiple System Atrophy, Cerebellar Type (MSA-C)

Question 33

Psychogenic Movement Disorders

Answer 33

• Key features:
  
  • Sudden onset
  • Variability – changing phenomenology (frequency, amplitude, direction)
  • Distractibility
  • Entrainment – will change in rhythm to match other movements
  • Coherence – all body parts moving to the same rhythm
  • Suggestibility
• Not uncommon – up to 10% of new pt visits in movement disorders clinic
• Risk factors:
  
  • Having other neurologic conditions
  • Recent significant stress/trauma (emotional or physical)
  • Psychiatric disorders
  • H/O childhood abuse/neglect
• Treatment consists of engaging the pt in the diagnosis, physical therapy, psychiatric care, and psychotherapy

Question 34

Movement Disorders

Take Home Points

Answer 34

• Dopamine acts on the basal ganglia on both the indirect and direct pathways to facilitate movements
• Parkinson’s disease and other movement d/o are clinical diagnoses
  
  • Based on carful hx and PE
• Parkinson’s disease has many available treatments
  
  • With appropriate management, pts can sustain a good QOL