Dr Jeff Beckman Advanced Parkinson disease

Advanced Parkinson disease : Advanced Parkinson disease Dr Jeff Beckman


Objectives : Objectives Review clinical manifestations motor and nonmotoric Discuss pathophysiology Discuss diagnosis and investigation Discuss management


Clinical manifestations : 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 : Gait abnormalities FREEZING Leg trembling Inability to initiate walking Moving forward with small steps Noted when turning and going thru small spaces


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


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


Speech : Speech Hypophonia Dysarthria Palilalia Tachyphemia


Speech : 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 : Dysautonomic symptoms Orthostatic hypotension Constipation Urinary incontinence Sexual Dysfunction Late manifestations of Parkinson


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


Blood pressure : 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 : 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 : 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 : 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 : 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 : Psychiatric Depression 35-50% Anxiety 35% Does not correlate with dopamine deficiency


Risk for dementia : 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 : 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 : 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 : Sleep disorder Found in >75% of patients


Sleep disorders : Sleep disorders Increased day time sleepiness Disruption of circadian rhythms Dopamine meds Poor night time sleep


Night time sleep disorders : 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 : 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 : Differential diagnosis Parkinson plus (MSA) 12% Striatalnigral degeneration Shy Drager Autonomic involvement Progressive supranuclear palsy PSP


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


Slide32 : If recent increase confusion think drugs or medical cause of delirium Increase in dysarthria or imbalance and freezing think dopamine toxicity


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


Dose failure : 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


Slide37 : 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


Slide38 : 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


Slide39 : New drug on the block – rasagiline MAO B inhibitor Moderate symptomatic relief Possible preventative ??? Would not use in advanced PD


Slide40 : 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


Slide41 : Asymmetric parkinson tremor Thalamic nerve stimulator


Slide42 : Dopamine transplant of tissue to date no significant benefit


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


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


Imbalance and freezing : Imbalance and freezing Meds unhelpful occ too much levodopa Walk with assistance Wheeled walker for freezing


Bladder dysfunction : 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 : Constipation Mild—exercise,adequate fluid intake, bran Moderate---stool softeners and bulk forming agents Severe -- lactulose glycerin suppositories


Impotence : Impotence Sildenafil etc. Tolerated Urologic assessment may helpful


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


Sleep Disorders : 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 : 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 : Agitation and psychosis Quetiapine Donepezil Trazodone valproate


Cognition : Cognition Cholinesterase inhibitors - Donepezil Galantamine rivastigmine


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