Advanced Parkinson

disease
 Objectives
 Review clinical manifestations motor
and nonmotoric
 Discuss pathophysiology
 Discuss diagnosis and investigation
 Discuss management
 Clinical manifestations
 Mild-moderate tremor,
rigidity,bradykinesia and postural reflexes
 Severe Gait abnormalities
 Imbalance
 Dysarthria and dysphagia
 Autonomic symptoms
 Cognitive difficulties
 Depression
 Sleep disorders
 Gait abnormalities
 FREEZING
 Leg trembling
 Inability to initiate walking
 Moving forward with small steps
 Noted when turning and going thru
small spaces
 Freezing
 Often occurs as an off phenomena
 May be independent of bradykinesia
and tremor
 Occasionally adverse effect of
levodopa
 Imbalance
 Unrelated to freezing
 Unsteadiness when turning
 Severe retropulsion requiring
assisted ambulation
 Usually unrelated to Parkinson meds
 Postural hypotension occasionally
plays role
 Speech
 Hypophonia
 Dysarthria
 Palilalia
 Tachyphemia
 Speech
Palilalia and hypophonia most often
not affected by drugs
Occasionally improved during on times
Dysarthria and tachyphemia may be
related to higher levodopa dosing
Dysarthria complicated mechanism –
dyskinesia ,hypokinesia or left
subthalamic stimulation
 Dysautonomic symptoms
 Orthostatic hypotension
 Constipation
 Urinary incontinence
 Sexual Dysfunction
 Late manifestations of Parkinson
 Dysphagia
 Common in advanced disease
 Slowness in propelling food to
pharynx
 Pooling of material near tonsillar
pillars
 Silent aspiration
 Blood pressure
 Dizzy or faintness due to postural
hypotension 10-20%
 Degeneration of autonomic ganglia
 Parkinson meds may exacerbate
 Hypertension during off periods may
occur
 Supine hypertension think MSA
 Constipation
 Common
 May be initial manifestation of
parkinsons
 Meds a factor
 Unresponsive to standard
antiparkinson drug treatment
 Poor control of pelvic floor muscles
and contraction external sphincter
 Anismus inability to defecate when
off
 Urinary symptoms
 25% of men
 Urgency most common
 Obstructive symptoms less common
 Uninhibited bladder and detrusor
dyssynergia seen on urodynamic
studies
 Not related to motor effects of
parkinsons
 Sexual dysfunction
 Decreased mucosal lubrication
 Premature ejaculation
 Delayed ejaculation
 Erectile dysfunction
 Hypersexuality or sexual delusions
due to levodopa or dopamine
agonists
 Can occur in isolation or be a
prodrome to more severe drug
induced psychosis
 Cognitive difficulties
 20-40%
 Sub cortical dementia
 Selective difficulties with
memory,slowing of cognition and
problems with abstraction,reasoning
and cognitive shifts
 Memory aided with written notes
 Language,calculation,constructional
tasks and problem solving later
manifestations
 Psychiatric
 Depression 35-50%
 Anxiety 35%
 Does not correlate with dopamine
deficiency
 Risk for dementia
Advancing age
Late age of onset of disease
Severe motor findings
Coexisting depression
Low verbal fluency
Early executive dysfunction and or
hallucinations
 Hallucinations
 30% of patients
 Mainly visual
 Some realize they are not real others
are threatened by them
 Risk factors old age,sleep
disturbance,treatment with
dopaminergic meds and cognitive
impairment
 Lewy body dementia
Dementia onsets with parkinson
features
Visual hallucinations present
Cognition fluctuates
Early onset of visual spatial
difficulties,speed of cognitive
processing and problem solving
Older age of onset
More common in males
 Sleep disorder
 Found in >75% of patients
 Sleep disorders
 Increased day time sleepiness
 Disruption of circadian
rhythms
 Dopamine meds
 Poor night time sleep
 Night time sleep disorders
 REM sleep behavior disorder
 Night time motor symptoms
 Nocturnal or early morning dystonia
 Dopamine medication- insomnia and or
hallucinations
 Periodic leg movements
 Restless leg syndrome
 Depression
 Obstructive or central sleep apnea
 Pathophysiology
 Starts in lower brainstem and spreads
superiorly autonomic neurons
constipation
 Serotonergic and noradrenergic abn seen
in upper brainstem neurons - Effect on
sleep and mood
 Dopamine neuron loss substantia nigra-
motor
 Amygdala hypothalmus and basal
forebrain –mood and cognition
 Cortex - mood and cognition
 Differential diagnosis
 Parkinson plus (MSA) 12%
 Striatalnigral degeneration
 Shy Drager Autonomic involvement
 Progressive supranuclear palsy PSP
 Differential diagnosis
 Multiinfart deep white mater or basal
ganglia
 Corticobasal ganglionic degeneration
 Normal pressure hydrocephalus
 Lewybody alzheimer disease
 Drug induced
 If recent increase confusion think
drugs or medical cause of delirium
 Increase in dysarthria or imbalance
and freezing think dopamine toxicity
 Investigation
 Cat scan if atypical history or signs
 Balance or cognitive difficulties noted
earlier than expected
 Stroke ,tumor, subdural hematoma
or NPH
 Prognosis and complications
 Pneumonia
 Urosepsis
 Hip fractures 27% lifetime risk
 Falls - brain trauma
 Malnutrition 4 times more likely to
have 10 pound weight loss
 2-3 fold increase in early mortality
which depends on duration, age and
presence of dementia
 Management
 MOTOR PROBLEMS
 Wearing off
 Failure of levodopa dose taking effect
 Unpredictable off periods
 Dyskinesia on, biphasic or off
 dystonia
 Dose failure

 Take higher individual dose and on empty

stomach
 Increase dosing frequency
 Add dopamine agonist or COMT inhibitor
 Watch adverse effects –confusion
,hallucinations,postural hypotension,
dyskinesia and sleep excess
 Other - valvular heart disease with ergot
dopamine agonists pergolide
 Gambling and sexual disinhibition
 On dyskinesia decrease levodopa
dose may need to add dopamine
agonist
 On and off dyskinesia Amantadine
200-300mg per day
 Off dyskinesia dopamine agonist
,COMT inhibitor
 Dopamine Agonists ergot –
bromocryptine 60mg per day and
pergolide 5.0mg per day MAX doses
 Nonergot pramipexole upto 4.5mg
per day or ropinirole 24mg per day
Max doses
 New drug on the block – rasagiline
 MAO B inhibitor
 Moderate symptomatic relief
 Possible preventative ???
 Would not use in advanced PD
 Deep-brain Simulation Bilateral
subthalamic
 Need normal cognition
 Need to be levodopa responsive
 Patients with persistant freezing or gait
problems and severe dysarthria do not do
well
 Will increase on time and allow reduction
in levodopa dose ie less side effects and
dyskinesia
 Patient will not have better absolute motor
scores than with max levodopa
 Asymmetric parkinson tremor
Thalamic nerve stimulator
 Dopamine transplant of tissue to
date no significant benefit
 Speech impairment
 Speech therapy
 Speak more slowly
 Augmentative communication
devices
 Written notes
 Spouses hearing
 Occ dysarthria may mean too much
levodopa
 Dysphagia
 Watch for aspiration
 Barium swallow cine-esophagram
 Increased salivation anticholinergics
,botox salivary glands
 Gastrostomy may be necessary
 Imbalance and freezing
 Meds unhelpful occ too much
levodopa
 Walk with assistance
 Wheeled walker for freezing
 Bladder dysfunction
 Urgency, frequency,incontinence and
retention
 Progressive increase in postvoid residuals
 If urinary retention ruled out and frequency
is symptom can use peripherally active
anticholinergic oxybutynin
 Obstructive unresponsive to meds unless
rare case of levodopa responsive off anuria
 Urologic consultation rule out prostate
disease
 Patient may need intermittent cath to avoid
obstruction
 Constipation
 Mild—exercise,adequate fluid intake,
bran
 Moderate---stool softeners and bulk
forming agents
 Severe -- lactulose glycerin
suppositories
 Impotence
 Sildenafil etc. Tolerated
 Urologic assessment may helpful
 Postural hypotension
 Reduce drugs which may result in
decreasing BP dopaminergic if able
and other meds ie antidepressants
 High sodium diet, pressure
stockings,fludrocortisine and
midodrine(alpha agonist)
 Cognitive
 Rule out coexisting medical problems
 Dopamine toxicity visual
hallucinations, paranoid ideations,
reversal sleep wake cycle and
hypersexuality
 Ask about sleep difficulties
 Sleep Disorders
 REM behavior sleep disorder -
clonazepam
 Sleep disruption secondary to
immobility-levodopa cr at bedtime
 Nocturnal and early am dystonia-
levodopa cr at bedtime occ use
baclofen
 Insomnia, vivid dreams –avoid night
time levodopa dose low dose
quetiapine
 Sleep Disorders
 Periodic leg movements- dopamine
agonist, levodopa cr,clonazepam
 Medication induced insomnia- lower
daily dose of dopaminergic meds,
schedule day time activities, non
contolled release levodopa, switch
agonist type,modafinal
 Depression mirtazapine (remeron)
 Obstructive sleep apnea
 Agitation and psychosis
 Quetiapine
 Donepezil
 Trazodone
 valproate
 Cognition
 Cholinesterase inhibitors -
 Donepezil
 Galantamine
 rivastigmine
 Summary
 Diagnose patients with idiopathic
Parkinson disease
 Identify and treat the many
problems associated with advanced
Parkinson disease