Movement Disorders Flashcards
Movement Disorders
- result of dysfunction or damage to portions of the brain (basal ganglia)
- to little movement (hypokinetic)
- to much unwanted movement (hyperkinetic)
- mixed movement disorders
Function of the Basal Ganglia
-Modulate Movement
Facilitate intended movements
Suppress unwanted movements
Hypokinetic Movement Disorders
- Parkinson’s disease
- Progressive supranuclear palsy
- Multiple system atrophy
Parkinson’s Disease: Demographics
-common neurological disease
100 per 100,000 people (2000 in above age 60)
-unknown etiology, genetic factors important if onset before age 50, others important if later (env.)
-typical age of onset: 55-65
-life expectancy (with treatment) nears normal
-10% develop symptoms before 40
Parkinson’s Disease: Neurologic Features
- asymmetric onset - eventually bilateral
- primary extrapyramidal features:
1. rest tremor
2. rigidity - inc. muscle tone in passive movement
3. bradykinesia - hard to start/stop movement, slow to cary out, hard to repeat motion
4. postural instability (late), balance impairment
Parkinson’s Disease: Motor Features
- secondary extrapyramidal features
- masked face - dec. facial expression
- diminished blink frequency
- stooped posture
- small-stepped, shuffling gait
- reduced armswing
- hypokinetic dysarthria - softer, slurred speech
- micrographia - smaller handwriting
Parkinson’s Disease: Non-Motor Features
- depression 40-50%, may precede motor
- anxiety 40%
- cognitive impairment (frontal lobe (executive)) with progression: if early not it
- executive: difficulty making decisions & carrying out plans
Parkinson’s Disease: Autonomic Dysfunction
- Gastrointestinal: constipation
- Urinary: over/under activing
- Sexual: ED in men, dec. libido
- Cardiovascular: orthostatic HTN
- Thermoregulatory: sweating
Parkinson’s Disease: Others
- olfactory dysfunction
- visual dysfunction
- sensory symptoms (pain)
- Sleep disturbances (sleep fragmentation, REM sleep behavior disorder)
- Fatigue
Parkinson’s Disease: Pathologic Features
- degeneration of pigmented neurons
- substantia nigra pars compacta
- locus ceruleus
- dorsal vagal nucleus
- Lewy body formation (cytoplasmic inclusion bodies) “fried egg” appearance
- central/enteric nervous system
- protein: alpha-synuclein (synucleinopathies)
Parkinson’s Disease: Neurochemical Features
- Dopamine deficiency (nigrostriatal, mesolimbic, hypothalamic, retinal)
- Norepinephrine
- Serotonin
- Glutamate
Progressive Supranuclear Palsy
- characterized by features of Parkinsonism but some additional ones
- Parkinsonism-plus syndrome
Progressive Supranuclear Palsy: Demographics
- sporadic
- prevalence is 1-6.5 per 100,000
- onset 50-60
- life expectancy is ~10 yrs
Progressive Supranuclear Palsy: Neurologic Features
Extrapyramidal Features
- Rigidity: especially axial rigidity, may produce neck hyperextension, symmetric
- Bradykinesia
- “Astonished” facial expression
- Dysarthria
- gait disturbance (early)
- postural instability (falling) (early)
- tremor is unusual
Progressive Supranuclear Palsy: Behavioral Features
- emotional lability
- dementia
Progressive Supranuclear Palsy: Ophthalmologic Features
- supranuclear gaze palsy
- vertical (downwardgaze) first (messy eater, “dirty tie” sign, difficulty descending stairs
- horizontal later
- oculocephalic reflex intact
- apraxia of eyelid opening (hard to open when asked, can do it spontaneously)
Progressive Supranuclear Palsy: Other Neurologic Features
- pyramidal tract signs (Babinski sign)
- sleep disturbances
Progressive Supranuclear Palsy: Pathologic Features
- Midbrain & cerebral cortical atrophy
- Neuronal loss & gliosis (multiple areas)
- Neurofibrillary tangles (globose type), composed of unpaired straight filaments, contain abnormally phosphorylated tau protein (tauopathy)
Progressive Supranuclear Palsy: Neurochemical Features
- striatal domamine deficiency
- dec. ACh, GABA, Norepinephrine
Multiple System Atrophy
-Parkinsonism-plus syndrome
Multiple System Atrophy: Demographics
- Sporadic
- Prevalence is 2.3-5.7 per 100,000
- symptom onset typically age 50-55
- life expectancy is ~5-10 yrs
Multiple System Atrophy: Neurologic Featuers
- present: parkinsonism, autonomic failure, or cerebellar syndrome
- Extrapyramidal (89%)
- Rigidity
- Bradykinesia
- Postural instability (early)
- Tremor is unusual
Multiple System Atrophy: Neurologic: Autonomic
78%
- urinary dysfunction
- orthostatic HTN
- impotence (males)
- gastrointestinal dysfunction
- thermoregulatory dysfunction
Multiple System Atrophy Neurologic - Cerebellar
55%
- ataxia
- dysarthria
- oculomotor abnormalities
- exaggerated rebound
Multiple System Atrophy: Neurologic - Pyramidal
61%
- hyperreflexia
- Babinski responses
- Spasticity
- Psuedobulbar palsy
Multiple System Atrophy: Neurologic - Behavioral
22%
- personality changes
- depression
- cognitive dysfunction (frontal lobe executive dysfunction)
- dementia typically does not develop
Multiple System Atrophy: Neurologic - Other
- respiratory stridor, vocal cord abductor weakness, 33%, inc. sudden nocturnal death
- involuntary sighing
- Raynaud’s phenomenon
- postural myoclonus of the hands
Multiple System Atrophy: Pathologic Features
- Cell loss & Gliosis: basal ganglia, brainstem, cerebellum, spinal cord
- Glial cytoplasmic inclusion bodies
- alpha-synuclein
Multiple System Atrophy: Neurochemical Features
-not well characterized
Hyperkinetic Movement Disorders
- Huntington’s disease
- Tourette’s Syndrome
- Primary (idiopahtic) Dystonia
Huntington’s Disease: Demographics
- autosomal dominant inheritance (mutation on short arm of chromosome 4, expanded trinucleotide repeat, codes for “huntingtin” protein
- onset 35-45
- younger age of onset associated with more rapid course
- after symptoms: life 15-20 yrs
Huntington’s Disease: Neurologic - Extrapyramidal
- chorea is common early
- dystonia emerges as disease progresses
- hyperkinetic dysarthria
- Parkinsonism (juvenile form is onset)
- Parkinsonism (advanced disease in adults)
Chorea
-rapid, random jerky movements that seem to flow from one movement into another & impart a restless “wiggly” or dancing appearance to patient
Dysarthria
-result of choreiform movements of the tongue & lips interfering with speech
Huntington’s Disease: Neurologic - Behavioral
- personality changes (impulsiveness, irritability, obsessive behavior, aggression)
- depression
- dementia (executive dysfunction, impairment of planning, organizing, reasoning, abstraction, judgement)
Huntington’s Disease: Other Features
- Oculomotor Disturbances (difficulty initiating saccades, slowed saccades, glazed impersistence)
- Cachexia
Huntington’s Disease: Pathologic Features
- striatum (especially caudate), atrophy, neuronal loss, gliosis
- cortex - atrophy, neuronal loss
Tourette’s Syndrome: Demographics
100-1000 per 100,000
- genetic mutation identified in a small fraction of patients; suspected in many more
- 3:1 male predominance
- symptom onset b/w age 2-15
- symptoms often diminish in adulthood
- normal life expactancy
Tourette’s Syndrome: Clinical Features
- Motor tics (stereotypic, sudden movements), may be simple or complex, preceded by a premoition or urge, may be temporarily suppressed
- Vocal (phonic) tics - similar to motor tics but involve sound rather than movement
- Sensory tics - may occur
- Tics vary in location, frequency, character, & severity over time
Tourette’s Syndrome: Formal Diagnostic Criteria
- Multiple motor tics & at least one vocal tic must be present at some point during the course, though not necessarily concurrently
- Tics must occur many times per day, almost every day or intermittently over the course of more than a year, wit no tic-free period of greater than 3 consecutive months
- Onset must be before age 18
- The disorder must not be explained by any other condition
Motor Tics
Simple: muscle jerks, head shaking, shoulder shrugging, eye blinking, lip pouting
complex: jumping, throwing, clapping, touching, echopraxia (mimic others movement), copropraxia (obscene or forbidden gestures)
Vocal Tics
Simple: sniffing, grunting, barking, hissing, clearing throat
Complex: words, phrases, sentences, echolalia (mimic vocal), palilalia (rapid repetition or echoing of one’s own words), coprolalia (swearing or obscene derogatory words)
Tourette’s Syndrome: Behavioral Features
- Attention deficit hyperactivity disorder: 35-90% of children with TS
- Obsessive-Compulsive disorder: 30-50% of persons with TS
Tourette’s Syndrome: Pathologic Features
-no abnormality has been identified y
Tourette’s Syndrome: Neurochemical Features
- no definitive abnormality
- some dopaminergic disturbance suspected
- others: monoaminergic (norepinephrine, serotonin,), opioid, adenosine
Dystonia
-sustained muscle contraction that produces sustained, & sometimes repetitive, twisting movements that result in abnormal posture
Dystonia can be Classified by?
- Etiology: primary (unknown) & secondary (disease)
- Topographic distribution: generalized (muscles throughout the body) & focal (only one or a group)
Dystonia: Demographics
- estimated prevalence is 3 per 100,000
- onset during childhood
- Ashkenazi Jews
- autosomal dominant inheritance (DYT1 gene mutation on chromosome 9, glutamate deletion in the protein, Torsin A, penetrance rate is 30-40%)
- other mutations have also been identified
Dystonia: Neurologic Features
- focal onset
- initially is action dystonia
- lower extremity usually involved first (ankle inversion, plantar flexion of the toes)
- axial muscles subsequently involved
- gait & posture abnormalities develop “dromedary” appearance to gain, exaggerated hip abduction, knee hyperextension”
- eventually these postures become fixed
- dystonia remains sole feature (except for tremor in some)
Dystonia: Pathologic Features
-no consistent abnormality
basal ganglia or cerebellum is origin
Dystonia: Neurochemical Features
- no consistent abnormality
- some studies show: dopamine, norepinephrine, GABA
Primary Focal Dystonia: Demographics
- adult onset
- traditionally considered to be sporadic
- genetic basis recently has been identified in some
- 30 per 100,000
Primary Focal Dystonia: Neurologic Features
- various muscle groups affected
- muscles are usually above the waist
- typically progress over several years, then static
- may be task-specific
- may be relieved by sensory tricks
- Cranial dystonia (Blepharospasm, Oromandibular, Laryngeal (spasmodic dysphonia))
- Cervical Dystonia (spasmodic torticollis)
- Limb Dystonia (Writer’s cramp, Musician’s dystonia)
Primary Focal Dystonia: Pathologic Features
-no consistent abnormality
Primary Focal Dystonia: Neurochemical Features
-no consistent abnormality
Mixed Hypokinetic-Hyperkinetic Movement Disorders
-Wilson’s Disease
Wilson’s Disease: Demographics
- 3 per 100,000
- 1 in 90 is a carrier
- autosomal recessive inheritance (mutation long arm of chromosome 13, gene product is ATP7B, copper-transporting APTase, 380 mutations identified)
Wilson’s Disease: Presentation
-onset 10-20, early as 3, late as 70s
-clinical presentation:
hepatic, neurologic, psychiatric
Wilson’s Disease: Hepatic Features
- acute transient hepatitis
- acute fulminant hepatitis
- chronic active hepatitis
- progressive cirrhosis
Wilson’s Disease: Neurologic Features
- parkinsonism
- chorea
- dystonia
- kinetic (intention) tremor
- dysarthria
- incoordination
Wilson’s Disease: Psychiatric Features
- personality change
- depression
- mania
- psychosis
- dementia
Wilson’s Disease: Ophthalmologic Features
- Kayser-Fleischer rings: brown pigment around the outer rim of the cornea (Cu deposits in Descemet’s membrane)
- Sunflower Cataracts: only seen on slit-lamp exam, due to Cu deposits in the lens
Wilson’s Disease: Pathologic Features
- Cu deposition in various tissues
- Hepatic fibrosis & cirrhosis
- Neuronal loss & gliosis (putamen, thalamus, cerebral cortex)
- Opalski cell formation (may originate from degenerating astrocytes)
Opalski Cell
Seen in Wilson’s Disease
Wilson’s Disease: Chemical Features
- dec. serum ceruloplasmin
- inc. serum free copper (dec. serum total copper, because of dec. ceruloplasmin)
- inc. urinary copper
- inc. hepatic Cu
