Movement Disorders Flashcards
What subcortical gray-matter structures constitute the basal ganglia and are involved in movement disorders?
striatum (caudate nucleus and putamen), globus pallidus, subthalamic nucleus, substantia nigra
What neurotransmitters are crucial in the basal ganglia?
- Dopamine
- Acetylcholine
- GABA
What are functions of the extrapyramidal tract?
- Modulates the corticospinal tract
- Promotes, inhibits, and sequences movement
- Maintains muscle tone and posture
What is hypokinesia versus hyperkinesia?
Forms of dyskinesia
Hypokinesia - too little movement, such as in PD and parkinsonism, associated with bradykinesia and akinesia
Hyperkinesia - excessive movement, often in the form of tremor, athetosis, chorea, hemiballismus
What are the cardinal and classic signs of Parkinson’s disease (PD)?
- Tremor, usually slow and pill-rolling
- Rigidity, cogwheel or lead-pipe
- Bradykinesia, absence of reduction of arm swinging when walking, absence or reduction of gestures when talking
- Postural instability
Other signs include:
masked facies; hypophonia, micrographia, shuffling gait, dysphagia
What are two types of postural instability?
- Fixation disorder: inability or difficulty in maintaining a part of the body in normal position
- Equilibrium disorder: difficulty standing or sitting unsupported
Do movement symptoms in PD appear unilaterally or bilaterally?
- Typically first develop in asymmetric or unilateral pattern
- As disease progresses bilaterally, it continues to predominate on the side initially involved
What is the neuropathology of PD?
- Loss of DA cells in substantia nigra, particularly the lateral ventral tier; leads to DA depletion in striatum, affecting dorsolateral putamen mostly
- Lewy bodies in substantia nigra
- alpha-synuclein pathology outside the nigro-striatal system affecting the autonomic nervous system, lower brainstem, limbic system, and olfactory bulbs; may contribute to nonmotor syptoms
Risk factors for PD?
- viral encephalitis
- drugs with DA antagonistic properties
- toxic substances
- expsoure to MPTP, herbicides, pesticides, manganese, iron
- drinking contaminated well water
- genetic mutations - linked to parkinsonism
How many patients with PD develop dementia?
20-30%
What are risk factors for developing dementia in PD?
- Age over 70
- UPDRS score >25
- Comorbid depression
- Levodopa side effects of mania, agitation, disorientation, or psychosis
- Facial masking at presentation
- Cerebrovascular disease
- low SES
- Initial symptoms other than tremor
How many patients with PD have depression?
Up to 40%
What’s the age of onset for PD and age-related impact on disease course?
- Onset before 40-45 has slower progression, fewer cognitive difficulties
- Later onset has more rapid progression and more cognitive deficits
How do PD subtypes impact disease course?
- Tremor dominant subtype has a more benign course
- Nontremor subtype, including bradykinesia and rigidity as primary sx, disease more likely leads to dementia
What are the earliest motor and nonmotor signs of PD?
- numbness, pain, difficulty with dexterity, changes in handwriting
- decreased smell, hyposomnia, sleep disorders, constipation
Describe the stages of PD?
Stage 1: unilateral sx, usually tremor, mild, not disabling
Stage 2: bilateral sx, minimal disability, posture and gait affected
Stage 3: slowing of mvmnt, poor equilibrium, moderate dysfunction
Stage 4: severe sx, limited walking ability, rigidity, bradykinesia, unable to live independently, tremor may lessen
Stage 5: cachectic stage, cannot stand or walk, requires constant nursing care
What are treatment considerations in early to middle stages of PD?
- Medications: selegiline, dopamine agonists, coenzyme Q10 early on, adding levodopa
- Nonpharmacological: exercise, voice therapy, speech/swallowing therapy, biofeedback, balance exercises
What are treatment considerations in late stages of PD?
- Medication combinations
- Deep brain stimulation
- Pallidotomy, thalamotomy, subthalamotomy
- Assistive devices
- Treatment of nonmotor sx
What are expectations for neuropsych assessment results in PD?
- Intelligence: intact
- Attention: slowed complex attn, impaired working memory
- Processing speed: impaired
- Language: reduced output, naming gradually declines later stages
- Visuospatial: micrographia, poor perceptual judgment, angular orientation, constructional praxis
- Memory: impaired initial learning but benefits from cues, recognition, recall aids
- EF: impaired
- Sensorimotor: impaired
- Emotional: depression and anxiety are common
How many patients with PD respond to levodopa?
Almost 80% show improvement with levodopa
What psychotic symptoms may occur in PD?
- PD patients may have visual hallucinations that usually fluctuate throughout the daytime and worsen at night, typically include visions of people and animals
- Psychosis in PD correlates with dementia, illness duration, and severity, number and strength of dopaminergic meds, signs of excessive medication
How much of a role do genetic factors play in PD?
- only 10-15% of PD patients have a first-degree relative with PD
- only 5% have an identified genetic cause
- More significant role when onset occurs before age 50
What genetic marker is associated with Huntington’s (HD)?
- Autosomal dominant pattern
- CAG trinucleotide repeats (>36) on chromosome 4
- Number of CAG repeats is inversely related to age of onset
- between 36-40 repeats is reduced penetrance (+/- affected), while >40 is full penetrance
What are core motor sx of Huntington’s?
- Chorea
- Bradykinesia
- Dystonia
- Incoordination
What are psychiatric sx of Huntington’s?
- depression
- obsessive-compulsiveness
- apathy
- psychosis
- sleep disturbance
What is the neuropathology of Huntington’s?
- Loss of medium spiny cells, sparing of interneurons, in caudate nucleus
- Indirect BG thalamocortical circuitry is most affecting
- Degeneration of striatal circuits later in disease
- decreased brain volume, up to 25% at death
What is the age of onset, range, and duration for Huntington’s?
- Onset 30-50
- Range 2-85
- Duration 17-20 years
Describe the stages of Huntington’s
- Stage 1: chorea most prominent; pt still independent; death is rare but contemplation of suicide possible
- Stage 2: generalized motor disturbance; physical and psychological family burden; death occurs via suicide or complications
- Stage 3: severe generalized motor disturbance; pt completely dependent on care; physical burden on family; death
How prevalent are psychiatric comorbidities in Huntington’s?
- Depression, 40-50%
- Anxiety, 34-61%
- Other features include irritability, obsessive/compulsive, psychosis
Expectations for neuropsych assessment results in Huntington’s?
- Intelligence: preserved until late stages
- Attention: impaired early
- Processing speed: severely impaired
- Language: slowed speech can progress to mutism
- Visuospatial: impaired
- Memory: significant learning deficits, intact recognition memory
- EF: severely impaired
- Sensorimotor: disturbed eye movements, inefficient visual tracking, impaired involuntary movements
- Emotional: depression, anxiety, psychosis, behavioral disturbance, obsessive-compulsive sx
When do cognitive changes appear in Huntington’s
- Changes can be detectable up to 15 years prior to clinical onset
- Psychomotor performance and attention/working memory are most sensitive
What types of treatment are used in Huntington’s?
- Dopamine receptor blocking or depleting agents can reduce chorea
- Overall there’s no cure or effective treatment
What is juvenile Huntington’s?
- Very uncommon, disease onset before age 20
- CAG repeats greater than 55
- Presents with behavior disturbances and learning difficulties
- Frequent epileptic seizures
- Can be misdiagnosed with psych problems
- In 75% of cases the father is affected parent
What is Lewy Body Dementia?
- Progressive neurodegenerative disorder characterized by parkinsonism and cognitive decline/dementia
- Second most common form of dementia after AD (20-30% have comorbid AD and LBD pathology)
- Onset in late 50’s, varies from 50-80
- Survival time 7 years (2-20 range)
Neuropathology of LBD?
- Lewy bodies and Lewy neuritis in the cortex and brainstem, quantified on scale of 0-4
- Pallor of substantia nigra
- Neuronal loss in hippocampus is variable
- Depletion of cholinergic neurons in the nucleus basalis of Meynert
What are risk factors for LBD?
- ApoE4 allele
- Males have higher incidence
Presentation and characteristics of LBD?
- Cognitive and parkinsonism sx onset within 1 year of each other
- Fluctuating cognition with marked variations in attention and alertness
- Recurrent visual hallucinations
- Parkinsonism
- REM behavioral disorder
- Neuroleptic sensitivity
- Psych sx
- Autonomic dysfunction
Expectations on neuropsych assessment of LBD?
- Intelligence: nonverbal IQ mild impairment
- Attention: impaired early
- Processing speed: impaired early
- Language: variable fluency and confrontation naming, hypophonia
- Visuospatial: markedly impaired early
- Memory: reduced but not as impaired as other domains until later in course
- EF: impaired early
- Sensorimotor: micrographia, parkinsonism
- Emotional: well formed visual hallucinations, delusions
What is Progressive Supranuclear Palsy (PSP) and it’s core presentation?
- Progressive neurodegenerative disorder
- Most common Parkinson’s plus syndrome
- Steel-Richardson-Olszeski syndrome
- Erosion of subcortical structures, subcortical-cortical connections
Sx include vertical gaze palsy, axial rigidity, postural instability with falls, dysarthria, dysphagia, gait disorder, early cog impairment, behavioral change
Neuropathology of PSP?
- Dopamine depletion in the substantia nigra, caudate, putamen
- Neuronal loss and gliosis in globus pallidus, subthalamic nuclei, red nuclei, dentate nucleus, superior colliculi, periaqueductal gray matter
- Neurofibrillary tangles and neuropil threads in BG, brainstem, dentate, nucleus basalis of Meynert
- Dopaminergic, cholinergic, and adrenergic neurotransmitter systems affected
- Disconnection of ascending pathways from subcortical structures to the prefrontal cortex
What is the age of onset and survival time in PSP?
- Onset in 60’s, can be early as 40’s
- Dementia in 50-80% of cases
- Survival 6-9 years, shorter with older age at onset
Presentation of PSP?
- Postural instability and falls
- Parkinsonism
- Oculomotor dysfunction - downward gaze
- Cog dysfunction within 2 years
- Early onset of gait problems
What are the most common subtypes of PSP?
- Richardson Syndrome
- PSP Parkinsonism
- PSP pure akinesia with gait freezing
What type of PSP has early onset supranuclear gaze palsy, postural instability, and neuropsych deficits?
Richardson Syndrome
What type of PSP has asymmetric onset, some response to levodopa?
PSP-Parkinsonism
What type of PSP has progressive gait disturbance, freezing of gait, speech, or writing; no tremor; rigidity; dementia or eye mvmnt abnormality in first 5 years?
PSP-Pure akinesia with gait freezing
What type of PSP has gait and balance problems early; less prominent midbrain atrophy but more prefrontal atrophy; nonfluent spontaneous speech, hesitancy, phonemic errors
PSP-Progressive non-fluent aphasia
What type of PSP includes cerebellar ataxia as the initial and main sx?
PSP-cerebellar
What type of PSP has asymmetric, progressive dyspraxia, cortical sensory loss, allien limb, limb dystonia, bradykinesia, unresponsive to levodopa
PSP-Corticobasal syndrome
What is the most common movement disorder?
-Essential tremor, which manifests as an action tremor and can be benign or a precursor to PD
How can essential tremor be differentiated from early PD?
-Dopamine transporter SPECT imaging
What are core features of Cortical Basal Degeneration (CBD)?
- Asymmetric motor sx
- Parkinsonism
- Tremor
- Limb dystonia
- Gait abnormality
- Myoclonus
- alien limb phenomenon
- cortical sensory loss
- Dyspraxia
How does CBD initially present?
- Either with motor sx, cognitive sx, or both
- Motor may be clumsiness of affected limb
- Apraxia spread to other side within 2 years
- Cog sx: impairment in language production, EF, and attention
What is the age of onset and survival in CBD?
- Onset in 60’s (range 50-70s)
- Survival 6-8 years
What characteristic traits of Tourette’s syndrome?
- Repetitive, stereotyped involuntary movements and vocalizations (tics)
- Tics must be present for at least 1 year
- Tics vary in type, frequency, and severity, and may worsen during illness, stress, fatigue, or excitement
- Usual onset btwn 2-12 years (avg. 7)
What is the gender difference in Tourettes?
Males are 3-4 times for affected than females
What are tics attributed to in Tourettes?
- Basal ganglia/cortical brain circuitry disorder
- Dopamine, serotonin, and norepinephrine may play a role
What are common comorbidities with Tourette’s?
- ADHD
- LD
- OCD
- depression, anxiety, panic attacks
- Sleep disorders
