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Management of Advanced

Parkinson’s Disease

Dr.Ratri Wulandari
 Meskipun ketersedian obat dan kemajuan pembedahan dapat megurangi gejala
Parkinson, penyakit ini akan secara tetap menyebabkan kecacatan yang progresif.
 Seiring dengan timbulnya kumpulan gejala Parkinson yang tidak responsif terhadap
levodopa.
 Gejala resisten ini termasuk ketidakstabilan postural dan jatuh, kesulitan berbicara dan
menelan, dan gejala non motoric (NMS)
Hoehn & Yahr

 Stage 1: gejala yang terjadi pada unilateral


 Stage 2: gejala pada kedua sisi tubuh tanpa disertai dengan gangguan keseimbangan
 Stage 3: perburukan keseimbangan, yang terjadi secara ringan atau sedang
 Stage 4: cacat, tetapi masih dapat berjalan atau berdiri dengan bantuan
 Stage 5: weel-chair bound or bed ridden
According to Symptomatology:
 Motor:
 Autonomic:
 Cognitive:
 Behavioral:
 Sleep:
 Other:
Motor:
 Motor complications (wearing off, on/off phenomena, dyskinesias)
 Axial Symptoms become most disabling (dysphagia, hypophonia, dysarthria, postural instability,
balance, frequent falls, freezing of gait)
Autonomic:
 Constipation
 Urinary Incontinence
 Sexual dysfunction
 Sialorrhea
 Orthostatic hypotension
Cognitive:
 Dementia
Behavioral:
 Psychosis
 Sever depression
 Sever anxiety, apathy
Sleep:
 REM sleep behavior disorder
 Excessive daytime sleepiness
 Restless leg syndrome
 Periodic limb movement
 Sleep disordered breathing
Motor complications:
 Wearing off: refers to the recurrence of motor and non-motor symptoms preceding the
scheduled dose of L-Dopa
 On-off fluctuations: are sudden unpredictable shifts between “well-” treated status (on)
and an undertreated state with severe Parkinsonism symptoms (off)
Management of wearing off and On-Off is focused on prolonging the effect of individual L-Dopa
doses:
 Fragmentation of dosing: up to 6-7 times a day at about 3-hour intervals
 Substitution of regular with controlled-release Ldopa
 COMT inhibitor (entacapone and tolcapone)
 MAO inhibitor (selegiline and rasagiline)
 Dopamine agonists: is generally contraindicated in late-stage disease.
 Continuous dopaminergic stimulation (CDS)
 Continuous infusion of levodopa/carbidopa gel through portable duodenal systems (Duodopa)
 The liquid effervescent levodopa formulation of melevodopa (methyl-ester levodopa)
Dyskinesias
 Involuntary choreiform and twisting movements
 occurring in patients undergoing long-term L-Dopa treatment.
 There are different types of levodopa-induced dyskinesias, such as the “peak-dose
dyskinesias”, “biphasic dyskinesias” and “wearing-off” dyskinesias
 Usually occur in “on” state, as chorea, myoclonus or dystonic movement.
 In end-stage patients dyskinesia may appear in off state as dystonic posture, especially in
the lower limbs.
Management:
 Lower the single L-Dopa dose
 Amantadine
 Clozapine: particularly useful when hallucinations are also present
 High-frequency subthalamic DBS (DBS-HFS)
Drug Failure Response:
 The efficacy of L-Dopa progressively decreases and patients may not respond at all to
administered doses.
 May be related to Degeneration of dopaminergic neurons poor gastric emptying and
insufficient intestinal absorption.
Management:
 Domperidone
 Low-protein dietary regimens
 shifting protein intake to the evening is an effective strategy
Autonomic complications:
 Constipation: in late stage can become particularly severe due to the combination of
anti-PD medications, slowed intestinal motility, immobility, and dehydration.
 Constipation should be well managed in order to avoid bowel occlusion and in order to
ensure proper absorption of L-dopa.
Dietary supplementation of fibers
Increased fluid intake
Macrogol (polyethylene glycol)
Urinary urgency or frequency
 Overactive bladder is the result of loss of normal inhibition by the basal ganglia and the
frontal cortex to the sacral spinal cord
 Anticholinergics: are commonly used, although their use should be discouraged in late-
stage patients due to cognitive and other anticholinergic adverse effects.
◦ Trospium (Trospikan 20mg) : Newer generation of peripheral anticholinergics, better
tolerated and can be used even in advanced patients.
◦ Botulinum toxin injections in the detrusor muscle
Orthostatic Hypotension (OH)
 Fall in systolic blood pressure below 20 mmHg and diastolic pressure below 10 mmHg within 3
minutes of standing
 Presents in severe cases with lightheadedness or syncope, exposing the patient to high risk of
fall.
Management:
 ◦ Avoiding rapid changes of position or straining during micturition or defecation
 ◦ Fluid intake, particularly in the morning, should be maintained at around 2L of water daily and
at least 8g of sodium chloride
 ◦ Elastic stocking and abdominal binders can be helpful
 ◦ Plasma volume expander, like fludrocortisone, and vasoactive agents, like midodrine.
Dysphagia:
 Severe dysphagia may cause weight loss, malnutrition, dehydration, and increasing the
risk of aspiration pneumonia and death.
 Thickening agents, gelling agents, forming a gel that can be swallowed by patients.
 Supraglottic swallow maneuver, Super supraglottic swallow maneuver and Mendelsohn
maneuver
 PEG: (Percutaneous endoscopic gastrostomy) to guarantee to patients' adequate food
and fluid intake as well as dopaminergic therapy through infusion.
Sialorrhea:
 caused by impaired or infrequent swallowing, rather than hypersecretion.
 Anticholinergics (glycopyrrolate and scopolamine)
 Botulinum Toxin: Intraglandular injection of botulinum toxin type A.
 Surgery to denervate the salivary glands: performed through the middle ear, where the
tympanic plexus and chorda tympani travel before entering the major salivary glands. The
procedure is relatively simple and fast, Unfortunately, salivary function returns within six to
18 months, when nerve fibers regenerate
 Radiation to the salivary glands: a reasonable treatment option in elderly patients who are
not candidates for surgery and cannot tolerate medical therapy
Cognitive dysfunction:
 Cognitive difficulties may occur in up to 80% of PD patients, and dementia in
approximately 30%, making this condition a very frequent non-motor complication.
Management:
 Begins with an evaluation to rule out other potential causes including depression,
infection, dehydration, and sleep disturbances.
 Rivastigmine and Donepezil, both were found to be moderately effective in PD dementia
 Memantine has not been shown to be effective in PD dementia and may worsen both the
motor and cognitive functions in PD
Behavioral Dysfunction:
 Depression:
 Depression is the most common psychiatric manifestation in Parkinson’s disease patients
with 40% prevalence.
 Diagnosing depression in Parkinson’s disease is often a challenge, as the clinical
symptoms of depression may be mistaken for those of Parkinson’s disease, such as flat
affect, psychomotor slowing, sleep disturbance, fatigue, and decreased libido.
 SSRIs are most frequently used as first line therapy.
 Tricyclic antidepressants can aggravate orthostatic hypotension and its anticholinergic
side effects can worsen cognitio
Psychotic symptoms:
 All the medications used to treat Parkinson’s disease have the potential to induce
hallucinations.
◦ It is recommend to stop anticholinergic medication first. The other drugs, in the order of
stopping priority, are amantadine and monoamine oxidase inhibitors, dopamine
agonists, and then, L-dopa.
◦ Quetiapine and Clozapine are preferred for use in PD with psychotic symptoms
◦ Other atypical & typical antipsychotic agents antipsychotics should be avoided due to
worsening of motor function
Anxiety:
 Anxiety disorders occur frequently in patients who experience “on-off” motor fluctuations,
especially during the “off” phase, suggesting that anxiety may be a reaction to motor
symptoms.
 While the optimal pharmacologic treatment for anxiety in Parkinson’s disease patients has
not been established, Commonly used medications include SSRIs, benzodiazepines, TCAs,
and buspirone