Guideline sources The following summarized guidelines for the evaluation and management of Parkinson's disease (PD) are prepared by our editorial team based on guidelines from the American Physical Therapy Association (APTA 2022), the Movement Disorder Society-European Section (MDS- ES/EAN 2022), the American Academy of Neurology (AAN 2021), the American Academy of Sleep Medicine (AASM 2021), the Canadian Neurological Sciences Federation (CNSF 2019), the American Association of Neurological Surgeons (AANS/CNS 2018), the British Association for Psychopharmacology (BAP 2017), and the European Neurological Society (ENS/EFNS 2013). 1 2 3 4 5 6 7 8 9 9 9 9 9 10 Definition PD is a chronic neurodegenerative disorder characterized by motor, cognitive and autonomic dysfunction, as well as mood and impulse control disorders. 9 Epidemiology The exact cause of PD is unknown; however, a combination of genetic and environmental factors have been implicated. Advancing age (>65 years), male gender, genetics (LRRK2, https://web.pathway.md/diseases/rec52HQxvSzXzVrkr 1/12 6/29/23, 10:53 PM Parkinson's disease Pathway glucocerebrosidase, and Parkin mutation), industrial exposure, heavy metals (manganese, copper, and lead), pesticides (rotenone, paraquat), and obstructive sleep apnea increase the risk of PD. 9 9 Pathophysiology The incidence of PD in the United States is estimated at 9.5-10.3 cases per 100,000 person- years, while its prevalence is estimated at 81 persons per 100,000 population. 10 Disease course In patients with PD, premature selective loss of dopamine neurons and accumulation of Lewy bodies causes the classical motor manifestations of parkinsonism (tremor, rigidity, bradykinesia, and postural instability), as well as autonomic dysfunction, cognitive dysfunction, and mood and impulse control disorders. 9 Prognosis and risk of recurrence Patients with PD have 2.56-fold increased risk of mortality than similar age-matched individuals. 9 Calculator Modified Hoehn and Yahr scale f Guidelines 1. Screening and diagnosis Indications for screening: insufficient evidence to recommend screening for premotor PD with olfactory testing, due to limited specificity. I Diagnosis: As per CNSF 2019 guidelines, suspect PD in patients presenting with tremor, stiffness, slowness, balance problems or gait disorders. B Show 4 more As per EFNS 2013 guidelines, use the Queen Square Brain Bank criteria for the clinical diagnosis of PD. B 2. Diagnostic investigations Diagnostic imaging: As per CNSF 2019 guidelines, do not obtain routine functional imaging for the differential diagnosis of PD and Parkinson-plus disorders, such as progressive supranuclear palsy and multiple system atrophy. D https://web.pathway.md/diseases/rec52HQxvSzXzVrkr 2/12 6/29/23, 10:53 PM Parkinson's disease Pathway Show 3 more As per EFNS 2013 guidelines, obtain transcranial ultrasound for the differentiation of PD from atypical and secondary parkinsonian disorders, for the early diagnosis of PD, and in the detection of subjects at risk for PD, although recognize that the technique is so far not universally used and requires some expertise. A Show 4 more Olfactory testing: As per CNSF 2019 guidelines, do not obtain objective olfactory testing for the diagnosis of PD. D As per EFNS 2013 guidelines, obtain olfactory testing to differentiate PD from other parkinsonian disorders. A Genetic testing: As per CNSF 2019 guidelines: Do not obtain routine genetic testing for monogenic parkinsonism. D Evaluate patients requesting genetic testing, particularly with young-onset parkinsonism, in a specialist movement disorders clinic for consideration of counseling and testing. B As per EFNS 2013 guidelines, obtain genetic testing for specific mutations on an individual basis, taking into account family history and age of onset. B Drug challenge tests: As per CNSF 2019 guidelines: Consider administering a trial of dopamine replacement therapy in patients initially considered to have a possible diagnosis of PD, to assist with an accurate diagnosis. C Do not perform acute challenge testing with levodopa or apomorphine for the diagnosis of PD. Consider initiating a trial of chronic levodopa treatment in patients with suspected PD. D As per EFNS 2013 guidelines, do not perform drug challenge tests for diagnosis of PD. Insufficient evidence to support the role of drug challenge tests in the differential diagnosis between PD and other parkinsonian syndromes. Screening for dementia and sleeping disorders: As per CNSF 2019 guidelines: Consider diagnosing dementia associated with PD and mild cognitive impairment in PD using the Movement Disorder Society clinical diagnostic criteria, with the use of reports of subjective cognitive decline and difficulties on psychometric testing. C Elicit a full sleep history in patients with PD reporting sleep disturbance. B As per EFNS 2013 guidelines, obtain an assessment of cognition and a screening for REM sleep behavior disorder, psychotic manifestations and severe depression as part of the initial evaluation of patients with suspected Parkinson's disese. A 3. Medical management General principles: Discuss the following before initiating treatment in patients with PD: https://web.pathway.md/diseases/rec52HQxvSzXzVrkr 3/12 6/29/23, 10:53 PM Parkinson's disease Pathway the patient's individual clinical circumstances, such as their symptoms, comorbidities and risks from polypharmacy the patient's individual lifestyle circumstances, preferences, needs and goals the potential benefits and harms of the different drug classes. B Show 4 more Levodopa: As per AAN 2021 guidelines, initiate levodopa as the initial preferential dopaminergic therapy in patients with early PD seeking treatment for motor symptoms. B Show 4 more As per CNSF 2019 guidelines, consider initiating levodopa as symptomatic therapy in patients with early PD. B Show 5 more Dopamine agonists: As per AAN 2021 guidelines, consider initiating dopamine agonists as the initial dopaminergic therapy to improve motor symptoms in selected patients with early PD aged < 60 years at higher risk for the development of dyskinesia. C Show 6 more As per CNSF 2019 guidelines, provide verbal and written information about the following and record the discussion with patients and their family members and caregivers (as appropriate) when initiating dopamine agonist therapy: the increased risk of developing impulse control disorders when taking dopamine agonist therapy, and that these may be concealed by the person affected the different types of impulse control disorders (such as compulsive gambling, hypersexuality, binge eating and obsessive shopping) who to contact if impulse control disorders develop the possibility that if problematic impulse control disorders develop dopamine agonist therapy will be reviewed and may be reduced or stopped. B Show 5 more MAO-B inhibitors: As per AAN 2021 guidelines: Counsel patients with early PD on the greater motor benefits of initial therapy with levodopa compared with MAO-B inhibitors to inform treatment decisions. B Consider prescribing MAO-B inhibitors as the initial dopaminergic therapy for mild motor symptoms in patients with early PD. C As per CNSF 2019 guidelines, consider initiating MAO-B inhibitors as symptomatic therapy in patients with early PD. B Show 2 more COMT inhibitors: Consider initiating catechol-O-methyltransferase inhibitors (entacapone) to reduce the off- time in patients with advanced PD having motor fluctuations. B Do not add entacapone to levodopa therapy for the purpose of delaying motor complications. D https://web.pathway.md/diseases/rec52HQxvSzXzVrkr 4/12 6/29/23, 10:53 PM Parkinson's disease Pathway Amantadine: Insufficient evidence to support the use of amantadine for the treatment of patients with early PD. I Offer amantadine (200-400 mg/day) for the treatment of dyskinesia in patients with later PD. A Other medications: Do not use anticholinergic drugs as first-line therapy in patients with early PD. D Consider offering -adrenergic antagonists, but not as drugs of first choice, as symptomatic therapy in selected patients with postural tremor. C Management of dementia: As per CNSF 2019 guidelines, consider adding cholinesterase inhibitors in patients with PD dementia: rivastigmine B donepezil B galantamine. C Show 3 more As per BAP 2017 guidelines: Offer rivastigmine and donepezil in patients with PD dementia. A Recognize that memantine produces global improvements in patients with PD dementia, but the pattern of cognitive and neuropsychiatric responsiveness remains uncertain. B Management of sleep disorders: As per AASM 2021 guidelines, consider offering the following medications for the treatment of adult patients with hypersomnia secondary to PD: modafinil sodium oxybate. C As per CNSF 2019 guidelines, advise good sleep hygiene in patients with PD with any sleep disturbance, including: avoiding stimulants (such as coffee, tea, caffeine) in the evening establishing a regular pattern of sleep ensuring comfortable bedding and temperature using assistive devices, such as a bed lever or rails, to aid with moving and turning allowing the person to get more comfortable restricting napping in the late afternoon and early evening advising regular and appropriate exercising to induce better sleep avoiding remaining in bed for long periods of time, if unable to sleep reviewing all medications and avoiding any drugs likely to affect sleep or alertness, or to interact with other medications (such as selegiline, H1RAs, H2RAs, antipsychotics and sedatives). B Show 6 more Management of depression: set a low threshold for diagnosing depression in patients with PD. Recognize that there are difficulties in diagnosing mild depression in patients with PD, as https://web.pathway.md/diseases/rec52HQxvSzXzVrkr 5/12 6/29/23, 10:53 PM Parkinson's disease Pathway the clinical features of depression overlap with the motor features of Parkinson disease. B Show 4 more Management of psychosis: obtain a general medical evaluation and offer treatment for any precipitating condition in all patients with PD and psychosis. B Show 10 more Management of autonomic dysfunction: consider administering botulinum toxin A for the symptomatic control of sialorrhea in patients with PD. B Show 5 more Palliative care: offer opportunities to discuss the prognosis of the condition in patients with PD and their family members and caregivers (as appropriate). Promote people's priorities, shared decision-making and patient-centered care during discussions. B Show 4 more 4. Nonpharmacologic interventions Physiotherapy: As per APTA 2022 guidelines, offer the following types of physical therapy interventions in patients with PD with corresponding purposes: Situation Guidance Improve oxygen consumption, reduce motor disease severity, and improve functional outcomes A Moderate-to-high-intensity aerobic exercises Reduce motor disease severity and improve strength, power, non-motor symptoms, functional outcomes, and quality of life A Resistance training Reduce postural control impairments and improve balance and gait outcomes, mobility, balance confidence, and quality of life A Balance training Improve ROM B Flexibility exercises Reduce motor disease severity and freezing of gait, improve gait outcomes A External cueing Reduce motor disease severity and improve non-motor symptoms, functional outcomes, and quality of life A Community-based exercises Reduce motor disease severity and improve stride length, gait speed, mobility, and balance A Gait training Task-specific training https://web.pathway.md/diseases/rec52HQxvSzXzVrkr 6/12 6/29/23, 10:53 PM Parkinson's disease Pathway Improve task-specific impairment levels and functional outcomes A Improve physical activity and quality of life. B Behavior-change approaches Show 4 more As per CNSF 2019 guidelines: Consider referring patients with early stages of PD to a physiotherapist with experience of the disease for assessment, education and advice including information about physical activity. C Offer physiotherapy specific to PD in patients experiencing balance or motor function problems. A Occupational therapy: Consider referring patients with early stages of PD to an occupational therapist with experience of PD for assessment, education and advice on motor and non-motor symptoms. C Offer occupational therapy specific to PD in patients having difficulties with activities of daily living. A Speech and language therapy: Offer speech and language therapy in patients with PD experiencing problems with communication, swallowing or saliva, including: strategies to improve the safety and efficiency of swallowing to minimize the risk of aspiration, such as expiratory muscle stress strategies to improve speech and communication, such as attention to effort therapies. A Augmentative and alternative communication devices: consider referring patients for alternative and augmentative communication equipment meeting their communication needs, as PD progresses and their needs change. C Dietary modifications: Advise patients a protein redistribution diet (eating most of the protein in the final main meal of the day) in patients with PD on levodopa experiencing motor fluctuations. Advise patients to avoid a reduction in their total daily consumption of protein. B Consider referring patients with PD to a dietitian for specialist advice. C Vitamins and dietary supplements: advise patients taking a vitamin D supplement. B Show 2 more 5. Therapeutic procedures Subcutaneous apomorphine infusion: As per EAN 2022 guidelines, consider offering apomorphine pump infusion in patients with advanced PD if fluctuations are not satisfactorily controlled with medication. E As per CNSF 2019 guidelines, consider administering subcutaneous apomorphine infusions or injections for the management of severe motor complications, only in units having sufficient experience and resources. C https://web.pathway.md/diseases/rec52HQxvSzXzVrkr 7/12 6/29/23, 10:53 PM Parkinson's disease Pathway Levodopa-carbidopa intestinal gel: As per EAN 2022 guidelines, consider offering levodopa-carbidopa intestinal gel in patients with advanced PD if fluctuations are not satisfactorily controlled with medication. E As per CNSF 2019 guidelines, consider administering intrajejunal levodopa-carbidopa enteric gel through percutaneous gastrostomy for the reduction of off-time or to reduce dyskinesia. C Deep brain stimulation: As per EAN 2022 guidelines, offer subthalamic nucleus deep brain stimulation in patients with advanced PD if fluctuations are not satisfactorily controlled with medication or if tremor cannot be controlled with medication. E Show 3 more As per CNSF 2019 guidelines, recognize that deep brain stimulation of the subthalamic nucleus or the globus pallidus interna is effective against motor fluctuations and dyskinesia. A Show 4 more As per CNS 2018 guidelines, consider performing bilateral subthalamic nucleus deep brain stimulation or bilateral globus pallidus internus deep brain stimulation in patients with PD undergoing surgery to treat motor symptoms. B Show 6 more 6. Surgical interventions Indications for surgery: As per EAN 2022 guidelines, consider offering unilateral pallidotomy with radiofrequency thermocoagulation in patients with advanced PD experiencing troublesome fluctuations, if deep brain stimulation and pump therapies are not treatment options. E As per CNSF 2019 guidelines: Consider offering unilateral pallidotomy for reducing contralateral dyskinesia. B Recognize that unilateral thalamotomy improves contralateral tremor and rigidity but has no consistent effect on akinesia. B Radiofrequency thermocoagulation: Insufficient evidence to recommend unilateral radiofrequency thermocoagulation of the thalamus for tremor or advanced PD. Do not perform this procedure if safer treatments are available, recognizing that deep brain stimulation has a better safety profile. I Do not perform unilateral radiofrequency thermocoagulation of the subthalamic nucleus in patients with PD because of the potentially high risks of adverse events. D Stereotactic radiosurgery: do not perform unilateral Gamma Knife radiosurgery of any of the three target nuclei in patients with PD because of the potentially high risks of adverse events. D Magnetic resonance-guided focused ultrasound surgery: insufficient evidence to recommend uni- or bilateral MRgFUS surgery of the thalamus for medically resistant tremor in patients with PD outside clinical trials. I https://web.pathway.md/diseases/rec52HQxvSzXzVrkr 8/12 6/29/23, 10:53 PM Parkinson's disease Pathway Show 2 more 7. Patient education General counseling: As per AAN 2021 guidelines, counsel patients with early PD on the benefits and risks of initial therapy with levodopa, dopamine agonists and MAO-B inhibitors based on the individual patient's disease characteristics to inform treatment decisions. B As per CNSF 2019 guidelines, communicate with patients with PD aiming to empower them to participate in the judgments and choices about their own care. B Show 5 more 8. Follow-up and surveillance Monitoring for medication adverse effects, levodopa: As per AAN 2021 guidelines, monitor patients taking levodopa routinely for motor response to treatment and for the presence of dyskinesia, motor fluctuations, impulse control disorders, excessive daytime sleepiness, postural hypotension, nausea and hallucinations, to guide dosage titration over time. B As per CNSF 2019 guidelines, monitor patients receiving levodopa or intermittent apomorphine for dopamine dysregulation syndrome. B Monitoring for medication adverse effects, dopamine agonists: As per AAN 2021 guidelines, screen patients taking dopamine agonists for the presence of adverse effects, including impulse control disorders, excessive daytime sleepiness, sudden- onset sleep, orthostatic hypotension, cognitive impairment and hallucinations, repeatedly during follow-up. B Show 4 more As per CNSF 2019 guidelines: Recognize that impulse control disorders can develop in patients with PD on any dopaminergic therapy at any stage in the disease course. B Obtain the following when an ergot-derived dopamine agonist is used: baseline echocardiographic screening and regular follow-up echocardiographic testing to identify cardiac abnormalities baseline laboratory (ESR, serum creatinine) and radiological (such as CXR) investigations with regular follow-up surveillance to identify serosal fibrosis. B Clinical findings Symptoms Past medical history Anxiety Orthostatic hypotension Bradykinesia Restless leg syndrome Constipation https://web.pathway.md/diseases/rec52HQxvSzXzVrkr 9/12 6/29/23, 10:53 PM Parkinson's disease Pathway Delusions Neurological exam Depression Asymmetric onset Difficulty speaking Asymmetry of disease Dysphagia Cognitive impairment Erectile dysfunction Cogwheel rigidity Fatigue Difficulty walking heel-to-toe Hallucinations Dysarthria Hyposmia Dystonia Inappropriate emotional responses Hypomimia Micrographia Loss of balance Muscular rigidity Shuffling gait Myerson's sign Sleeping disorder Postural instability Slow movements Resting tremor Stiffness of the limbs and trunk Speech disturbance Stuttering glabellar tap Urinary frequency Urinary urgency Past events Falls Musculoskeletal exam Stooped posture Likelihood Ratios Pertinent positives The following findings increase the probability of Parkinson's disease in adults. 11 Finding LR+ Value Positive glabellar tap 4.5 (2.8-7.4) History of shuffling gait 3.3-15 (3-15) Presence of difficulty walking heel-to-toe 2.9 (1.9-4.5) History of bradykinesia 1.9-5.2 Show 3 more Pertinent negatives The following findings decrease the probability of Parkinson's disease in adults. 11 Finding LR- Value Absence of muscular rigidity 0.12-0.93 Negative glabellar tap 0.13 (0.03-0.47) No history of tremor 0.24-0.60 No history of loss of balance 0.29-0.35 Show 4 more https://web.pathway.md/diseases/rec52HQxvSzXzVrkr 10/12 6/29/23, 10:53 PM Parkinson's disease Pathway References 1. 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