Transcript Neurodegenerative Movement Disorders

Neurodegenerative Movement
Disorders
Parkinsonism
Nancy L Diaz-Pechar, MD
Movement Disorder Center Director
Disclosure
• Dr. Nancy Diaz-Pechar has served as a
speaker for Teva pharmaceuticals
• There are no financial disclosures that
would be a potential conflict of interest
with this presentation.
Goals and objectives
• To understand how to distinguish between
atypical parkinsonism and Parkinson’s
disease
• To review clinical presentation and
treatment of progressive supranuclear
palsy, multiple system atrophy, and
corticobasal degeneration
• To briefly review the clinical presentation
and treatment of Huntington’s Disease
Parkinsonism
• Diagnosis remains to be clinical
• No imaging, genetic test, biomarkers
definitively diagnose
• Medical history, time-line, significant
clinical signs
• Given emerging clinical signs diagnosis
can change overtime as it become more
clear
• Bradykinesia
– An essential clinical sign as it implies an abnormal basal
ganglia-cortical neuronal circuit
– Slowness of initiation with progressive reduction in speed
– Decreased amplitude with repetitive movements.
– Exam: finger taps, rapid alternating movement, repetitive
hand opening, heel taps, toe tap (?pauses or freezing)
– Archimedes spiral, micrographia
– Hypomimia
– Reduced arm swing
– Poor dexterity
– Hypophonia
• Hypokinesia
– Slowed movements without decrement
• Extrapyramidal rigidity
– Increased resistance independent of velocity
• Lead pipe-constant
• Cogwheel- inconsistent
• Tremor
– 4-6 Hz rest tremor which ceases or attenuates
with action
– Asymmetric
– Re-emergent tremor- 5-10 sec
• Postural instability and gait disturbance
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Reduced speed
Imbalance
Narrow based, shortened stride
Decreased arm swing
Freezing (initiation, turn, doorway)
En bloc turning
Early sign in atypical parkinsonism
Lurching gait –PSP
Ataxia-MSA
Parkinson’s disease (PD)
• Clinical Diagnosis
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Bradykinesia plus at least one other symptom
Rest tremor
Extrapyramidal rigidity
Postural instability
• Shuffling, freezing, festination
– Typical parkinsonian features
• Unilateral
• Levodopa response
• Dyskinesia
• Autonomic disturbances: constipation/ gastroparesis,
urinary urgency, frequency, nocturia, incontinence, sexual
dysfunction, sweating, drooling
• Restless leg syndrome
• Sleep disorders: REM sleep behavior disorder (RBD),
excessive daytime sleepiness, insomnia
• Anosmia
• Fatigue/ Apathy
• Cognitive impairment
– Executive dysfunction/ MCI
– PDD
• Depression/ Anxiety
• Hallucinations/ psychosis
Medications and surgical
treatment options
• Carbidopa/levodopa (IR, CR, Parcopa, Rytary,
Duopa via JPEG pump)
• Dopamine agonist (ropinirole, pramipexol, Neupro,
apomorphine)
• Monoamine oxidase inhibitors (selegiline,
rasagiline, Zelapar)
• Catechol-O-Methyltransferase Inhibitors
(tolcapone, entacapone)
• Amantadine
• Anticholinergics (trihexyphenidyl, benztropine)
• Deep brain stimulation
• Various medications for nonmotor symptoms
Signs of Atypical Parkinsonism/
Parkinson-plus disorders
• Diagnosis based on clinical features and are
confirmed pathologically
• Signs it is not PD but rather an atypical
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Early postural instability/ gait disturbance
Rapid progression
Early dysphagia
Dysarthria is different than typical hypokinetic
changes seen with PD
– Paucity, absent or atypical tremor
– Poor or no response to levodopa
– Pyramidal tract findings (pseudobulbar palsy, UMN)
Progressive Supranuclear Palsy (PSP)
• Presenting sign is postural instability with early
falls (often backward)
• Slowed saccades/ supranuclear gaze palsy
(paralysis of voluntary vertical and later horizontal
gaze but preserve reflexive eye movements)
• Parkinsonism which is not usually levodopa
responsive and whose onset is typically symmetric
• Executive dysfunction/ frontal cognitive deficits
• Dysarthria
• Dysphagia
• Taupathy (abnormal accumulation of Tau
protein in brain)
• Slightly more common in men
• Average age of onset typically in 60’s (can
be as early as in 40’s)
PSP-subtypes
• PSP-Richardson syndrome
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Mean age of onset 65
Early postural instability and falls
Apathy/ personality changes
Visual changes
• slowed vertical saccades- hypometric saccades- square wave
jerks-supranuclear vertical gaze palsy
– Cognitive deficits
• Slowed processing
• Visuospatial dysfunction
– Dysarthria
– Dysphagia- aspiration
– Dependent on others within 3-4 years, mean duration 7
years
• PSP-parkinsonism
– Can be indistinguishable from PD at onset
– Bradykinesia and limb rigidity at onset
– Occasional jerky tremor
– Axial rigidity
– Early responsiveness to levodopa but this
typically dissipates over time
– Postural instability, cognitive deficits, and
supranuclear gaze palsy will occur later in the
first few years
• PSP-pure akinesia with gait freezing
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Less common
Bradykinesia mostly affecting gait/ freezing
Hypophonia
Hypomimia
Micrographia
Axial rigidity with no limb rigidity
Supranuclear palsy and blepharospasm occur
late
– Median duration- >10 years
• PSP-corticobasal syndrome
– Known only by pathological studies
– Presents as corticobasal ganglia degeneration
• PSP-frontotemporal dementia
– Less common
– Known due to pathological studies
– Behavioral variant frontotemporal dementia or
progressive nonfluent aphasia variant
– Typical PSP symptoms develop >5 years after
onset
PSP Treatment
• Medication trial (levodopa, amantadine, vesicare
for overactive bladder)
• Dystonia/ blepharospasm – consider neurotoxin
injections
• Diplopic- consider prism glasses
• Multidisciplinary care: neurologist, psychiatrist/
psychologist, PT/OT/ Speech, social worker,
palliative care
• Physical therapy/ Occupational therapy
– Strength, aerobic, and balance exercises, eye movement
exercises
– Fall prevention
• Train on wide, staggered stance to improve stability on anterior
to posterior weight shift
• Big steps, foot clearance, U-turns
• Avoid bending low/ standing quickly
• Scan area with eyes before walking
• Stop and move head and eyes to direction of turn before turning
– Heel wedge/ lift
– Assistive devices
• Rollator with brakes, wheelchair, scooter
– Environmental assessments/ home modifications
– ADL training
• Speech therapy
– Dysphagia
• Symptoms: delayed pharyngeal swallow onset, difficulty
seeing the whole plate, rapid drinking/ eating, rigidity or
hyperextended neck affecting self-feeding, difficulty
opening mouth, lack of insight to swallowing issue
• Mealtime swallow evaluation, video swallow study,
compensatory strategies such as repositioning, keeping
plate in line of vision, chin-tuck, mealtime adaptive
devices, altered diet, alternating between liquids and
solids, discuss feeding tube options with physician
– Communication
• Hypokinetic and spastic dysarthria, stained and
slow voice with impaired fluency, palilalia,
language and cognitive deficits, emotional lability
• Train to speak loudly and slowly (LSVT ), short
phrases, use gestures, yes/no questions,
communication board or speech generating
device, personal portable amplifier
Multiple System Atrophy (MSA)
• Prominent autonomic dysfunction
precedes motors signs by years
– Progressive bladder dysfunction (increased
frequency, urgency, incontinence, retention)
– Orthostatic hypotension
– Erectile dysfunction
– Constipation
– Difficulty with thermoregulation
• Parkinsonian phenotype
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Symmetric
Faster progression than PD
Postural instability , freezing, and falls within 3 years
Stimulus sensitive myoclonus > rest tremor
Bradykinesia, rigidity
Dysarthria and dysphagia
Dystonia
• Laryngeal- inspiratory stridor / vocal cord abductor paresis
• anterocollis
• Cerebellar phenotype
– Ataxic gait, limb/ truncal ataxia
– Nystagmus, jerky saccades
• Synucleinopathy (accumulation of alpha
synuclein protein)
• Mean duration- about 7-8 years but
actually varies so range is large
• Average age of onset is in the 50’s
• More common in men
• Sub-classified according to prominent
symptoms: MSA-C, MSA-P
MSA Treatment
• Levodopa trial (typically poor levodopa response but up to 1/3
have good response)
• Anterocollis
– Positioning, stretching, bracing
– Tilt wheelchair
• Treat hypotension
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d/c antihypertensive
Increasing salt intake
Compressive stockings
Fludrocortisone, midodrine, Northera
Elevate head of bed
Smaller more frequent meals
• Treat urologic issues
– Medications/ Botox for bladder spasticity
– Self cath/ suprapubic catherization
• Multidisciplinary care: neurologist, psychiatrist/ psychologist,
PT/OT/ Speech, social worker, palliative care
• Physical and Occupational therapy
– Large movements for bradykinesia (BIG)
– Gait training, U- turns, wide stance, fall
prevention, rising slowly
– ADL training/ functional mobility
• Avoid overreaching, sitting while dressing
– Assistive devices and home modifications
• Shower chair, grab bar, hand held shower head,
bed rail, etc.
• Speech therapy
– Dysphagia
• tendency toward bolus holding in oral cavity and discoordinated
bolus propulsion, difficulty sitting upright, increased pharyngeal
secretions, vocal fold motion impairment may compromise
airway protection
• Moist, soft food, chin-tuck, restrict bolus volumes, alternate food
and liquid, smaller more frequent meals, mealtime adaptive
devices
– Communication
• Hypokinetic dysarthria, hypophonia or ataxic or spastic
dysarthria
– LSVT, reduce rate of speech to improve coordination and
accuracy, communication board or speech generating
device, personal portable amplifier, yes/ no questions.
Corticobasal Degeneration/
Syndrome
• Affects the fronto-parietal cortex and the basal ganglia
• Signs and symptoms include
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Asymmetric ideomotor apraxia
Asymmetric rigidity and bradykinesia
Myoclonus, atypical tremor
Dystonia
Alien-limb phenomenon
Corticosensory deficits
Postural instability/ progressive gait changes until bedbound
Progressive aphasia
Mild cognitive or behavioral issues
Dysphagia
Dysarthria
Corticobasal Degeneration (CBD)
• Tauopathy
• Average age of onset in the 60’s but can be
as early as in 40’s
• Various phenotypes (overlapping features
with other disorders such as PSP, FTD, PPA,
posterior cortical atrophy, Alzheimer’s, etc..)
• Definitive diagnosis only by autopsy
• Mean duration 5-10 years from onset of
symptoms
CBD treatment
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Supportive to optimize function
Patient and caregiver education
Not responsive to dopaminergics
Treat myoclonus with antiepileptic
medications
• Treat dystonia with neurotoxin injections
with the goal of reducing pain and
improving hygiene
• Physical and Occupational therapy
– Stretching or bracing for anterocollis/ dystonia
– Encourage use affected limb (hand/ wrist
extension to maintain an open hand)
– Large movements for bradykinesia
– Gait training, U- turns, wide stance, Fall
prevention
– ADL training
– Assistive devices and home modifications
• Speech therapy
– Dysphagia
• Symptoms: slow or incomplete chewing and
swallowing, difficulty self feeding, oral and swallowing
apraxia
• Treated as in PSP
– Communication:
• Symptoms: hypokinetic and spastic dysarthria,
progressive apraxia, may have non fluent aphasia
• Encourage to use short phrases and simpler language,
write, yes/no questions, communication board
Huntington Disease
• Progressive, inherited, neurodegenerative
disorder with no cure
• Autosomal dominant, trinucleotide repeat
of CAG coding for glutamate, gene on
short arm of chromosome 4
• Anticipation
• Chorea- involuntary, irregular, rapid and unsustained
movements which flow between body parts
• Motor impersistence (milkmaid grip, tongue protrusion)
• Dystonia
• Ataxic gait
• Cognitive decline: impaired judgement, forgetfulness
• Dysarthria, eventually may be unable to speak but will
comprehend and retain awareness
• Dysphagia
• Psychiatric manifestations: personality changes, mood
swings and depression
Huntington’s disease Treatment
• Nothing alters course. No cure.
• Multidisciplinary care: neurologist, psychiatrist/
psychologist, PT/OT/ Speech, social worker, palliative
care
• Medications to lessen chorea
– Tetrabenazine, other antipsychotic medications such as
risperidone, olanzapine, haloperidol, etc..
• Medications for psychiatric disorders
– Antidepressants
• citalopram, fluoxetine, sertraline
– Antipsychotics
– Mood stabilizers
• valproate, carbamezapine, lamotrigine
• Physical and occupational therapy
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Strengthening and coordination exercises
Balance and gait , fall prevention
Posture
Respiratory exercises
Assistive devices: walker (add weights for chorea), wheelchair,
adaptive utensils, tub bench, foam grip, lift chair, etc.
– Adaptive improvement of ADL’s, caregiver training, improve
transfers
– Goal is to maintain cognitive, motor, and functional performance
• Speech therapy
– Impaired control of muscles of mouth and throat
– Mealtime swallow evaluation, video swallow study,
compensatory strategies such as repositioning, mealtime
adaptive devices, altered diet
– Speech and cognitive effects variable
Summary
• Diagnosis of the type of parkinsonism is
complicated as they are separate by subtle
changes in signs and symptoms. Careful
evaluation is required.
• Neurodegenerative movement disorders
discussed are progressive, and have no cure,
but diagnosis helps with patient and family
education, prognosis and guide specific
treatment.
• Multidisciplinary care is essential in caring for
patients with neurodegenerative movement
disorders.
• True or false
– Different subtypes of progressive
supranuclear palsy have been described, one
of which shows early responsiveness to
levodopa which dissipates over time.