Advanced Parkinson disease

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Advanced Parkinson disease

• Dr Jeff Beckman

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Objectives

• Review clinical manifestations motor and
  nonmotoric
• Discuss pathophysiology
• Discuss diagnosis and investigation
• Discuss management

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Clinical manifestations

• Mild-moderate tremor, rigidity,bradykinesia and
  postural reflexes
• Severe Gait abnormalities
• Imbalance
• Dysarthria and dysphagia
• Autonomic symptoms
• Cognitive difficulties
• Depression
• Sleep disorders

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Gait abnormalities

• FREEZING
• Leg trembling
• Inability to initiate walking
• Moving forward with small steps
• Noted when turning and going thru small spaces

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Freezing

• Often occurs as an off phenomena
• May be independent of bradykinesia and tremor
• Occasionally adverse effect of levodopa

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Imbalance

• Unrelated to freezing
• Unsteadiness when turning
• Severe retropulsion requiring assisted ambulation
• Usually unrelated to Parkinson meds
• Postural hypotension occasionally plays role

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Speech

• Hypophonia
• Dysarthria
• Palilalia
• Tachyphemia

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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

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Dysautonomic symptoms

• Orthostatic hypotension
• Constipation
• Urinary incontinence
• Sexual Dysfunction
• Late manifestations of Parkinson

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Dysphagia

• Common in advanced disease
• Slowness in propelling food to pharynx
• Pooling of material near tonsillar pillars
• Silent aspiration

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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

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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

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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

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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

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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

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Psychiatric

• Depression 35-50
• Anxiety 35
• Does not correlate with dopamine deficiency

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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

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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

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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

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Sleep disorder

• Found in gt75 of patients

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Sleep disorders

• Increased day time sleepiness
• Disruption of circadian rhythms
• Dopamine meds
• Poor night time sleep

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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

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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

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Differential diagnosis

• Parkinson plus (MSA) 12
• Striatalnigral degeneration
• Shy Drager Autonomic involvement
• Progressive supranuclear palsy PSP

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Differential diagnosis

• Multiinfart deep white mater or basal ganglia
• Corticobasal ganglionic degeneration
• Normal pressure hydrocephalus
• Lewybody alzheimer disease
• Drug induced

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• If recent increase confusion think drugs or
  medical cause of delirium
• Increase in dysarthria or imbalance and freezing
  think dopamine toxicity

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Investigation

• Cat scan if atypical history or signs
• Balance or cognitive difficulties noted earlier
  than expected
• Stroke ,tumor, subdural hematoma or NPH

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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

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Management

• MOTOR PROBLEMS
• Wearing off
• Failure of levodopa dose taking effect
• Unpredictable off periods
• Dyskinesia on, biphasic or off
• dystonia

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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

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• 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

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• 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

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• New drug on the block rasagiline
• MAO B inhibitor
• Moderate symptomatic relief
• Possible preventative ???
• Would not use in advanced PD

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• 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

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• Asymmetric parkinson tremor Thalamic nerve
  stimulator

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• Dopamine transplant of tissue to date no
  significant benefit

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Speech impairment

• Speech therapy
• Speak more slowly
• Augmentative communication devices
• Written notes
• Spouses hearing
• Occ dysarthria may mean too much levodopa

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Dysphagia

• Watch for aspiration
• Barium swallow cine-esophagram
• Increased salivation anticholinergics ,botox
  salivary glands
• Gastrostomy may be necessary

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Imbalance and freezing

• Meds unhelpful occ too much levodopa
• Walk with assistance
• Wheeled walker for freezing

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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

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Constipation

• Mildexercise,adequate fluid intake, bran
• Moderate---stool softeners and bulk forming
  agents
• Severe -- lactulose glycerin suppositories

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Impotence

• Sildenafil etc. Tolerated
• Urologic assessment may helpful

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Postural hypotension

• Reduce drugs which may result in decreasing BP
  dopaminergic if able and other meds ie
  antidepressants
• High sodium diet ,pressure stockings,fludrocortisi
  ne and midodrine(alpha agonist)

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Cognitive

• Rule out coexisting medical problems
• Dopamine toxicity visual hallucinations,
  paranoid ideations ,reversal sleep wake cycle and
  hypersexuality
• Ask about sleep difficulties

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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

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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

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Agitation and psychosis

• Quetiapine
• Donepezil
• Trazodone
• valproate

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Cognition

• Cholinesterase inhibitors -
• Donepezil
• Galantamine
• rivastigmine

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Summary

• Diagnose patients with idiopathic parkinson
  disease
• Identify and treat the many problems associated
  with advanced parkinson disease