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Disease/Disorder

See Parkinson Disease Part 1

Essentials of Assessment

See Parkinson Disease Part 1

Rehabilitation Management and Treatments

Available or current treatment Guidelines

The International Parkinson and Movement Disorder Society  has published an evidence-based review detailing the pharmacologic and non-pharmacologic treatments for motor symptoms in PD, across the various stages of the disease process.1  This society has also recently published an evidence-based review of interventions for non-motor symptoms.2

At different disease stages

New-onset/Acute        

Pharmacological Treatment

Motor Symptoms of Parkinson Disease Pharmacologic intervention in early PD is dependent on the level of functional impairment and requires careful consideration of benefits and side effects of each medication. In very early Parkinson Disease, pharmacologic management may not be used, and  dopaminergic medication is subsequently initiated when symptoms become bothersome to the patient.  Levodopa is the gold standard for dopamine replacement and treatment of motor symptoms. Other possible choices for initial treatment in younger patients include dopamine agonists, monoamine oxidase B inhibitors, and anticholinergic medications but these are typically less effective in treating symptoms and more likely to cause cognitive side effects in the elderly.2

Levodopa is administered with carbidopa to reduce peripheral breakdown of levodopa and reduce nausea. Levodopa/carbidopa comes in immediate release, extended release, orally disintegrating, and intestinal gel formulations. As PD progresses, more frequent and higher doses of levodopa are necessary. Levodopa-induced motor fluctuation and dyskinesias may be associated with higher daily doses of levodopa and longer disease duration.3,4

The catechol-O-methyl transferase inhibitors (tolcapone, entacapone, and opicapone) may be added to reduce breakdown of levodopa and combat on/off fluctuations.

Non-ergot dopamine agonists (pramipexole and ropinirole) have longer half-lives than levodopa and are used both as monotherapy and adjunctive therapy.4 Of note, 40% of patients treated with oral dopamine agonists have impulse control disorders and 15-20% experience withdrawal symptoms when discontinued.5 Patients should also be monitored for sleep attacks. There is also a transdermal option (rotigotine) and subcutaneous injection (apomorphine) used as a rescue medication for acute off periods.4

Monoamine oxidase B (MAO-B) inhibitors prolong the benefits of levodopa by preventing the breakdown of dopamine in the brain.2 Selegiline and safinamide may be used as adjunctive treatment for patients with motor fluctuations.  Rasagiline is used as a monotherapy or adjunctive therapy and has less symptom relief but lower dyskinesia risk.

Anticholinergic agents, (e.g. trihexyphenidyl hydrochloride and benztropine) may be used as initial medical therapy to treat tremor in younger patients, but are used less commonly in older individuals due to anticholinergic side effects of confusion, dry mouth, urinary retention, and constipation.3,4

Amantadine may be useful for levodopa-induced dyskinesia. An extended release formula is available.

Non-Motor Symptoms of Parkinson Disease

There are variable levels of evidence for the pharmacologic treatment of the non-motor symptoms of Parkinson Disease. Pharmacological management of non-motor systems should include careful consideration of the likelihood of efficacy and potential side effects. In dementia associated with Parkinson disease, rivastigmine is clinically useful while galantamine and donepezil are possibly useful.2,5 Depression may be treated with selective serotonin reuptake inhibitors, selective serotonin norepinephrine reuptake inhibitors, and tricyclic antidepressants. Pramipexole may be useful for some patients with depression. For patients with psychosis, many medications used in PD may contribute to psychosis, and thus should be considered for weaning depending on the clinical situation. These medications include anticholinergics, amantadine, dopamine agonists, MAO-B inhibitors, and sometimes levodopa. Pimavanserin, clozapine, and quetiapine are the three main options for treatment of psychosis in Parkinson disease, however clozapine requires specific monitoring due to side effects. 2,5 Melatonin is first line treatment for rapid eye movement sleep behavior disorder and clonazepam is used as well, when required, to improve sleep and reduce problematic behaviors.  Possibly useful treatments for orthostatic hypotension include fludrocortisone, midodrine, and droxidopa. 2,5 Botulinum toxin injections can be considered for sialorrhea. 

Cognitive behavioral therapy may relieve depression and anxiety.6 Mindfulness yoga can also assist with reducing these two psychological disturbances.7

Exercise and therapy

In general, exercise is recommended for all patients with PD and should be initiated early and continued throughout the disease course.5 Some evidence suggests that long term aerobic exercise may slow symptomatic progression of PD.4A study by Schenkman et al  demonstrated that high intensity treadmill exercise resulted in less decline on the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score compared with usual care, with data suggesting non-futility of high intensity treadmill exercise.8 Resistive exercises have been shown to ameliorate PD motor progression on the UPDRS for up to two years, and growing evidence shows that more intense forms of specific exercises lead to better outcomes.9,10 Forced exercise paradigms, such as tandem bicycle training, may improve motor function as well as bimanual dexterity.11

Postural and gait impairments have shown limited response to pharmacological and surgical treatments; thus, balance and gait rehabilitation are important adjuncts. Balance training and lower limb strengthening are recommended for balance impairment; modalities such as dance, Tai Chi and video gaming have all been shown to be beneficial.12,13 Axial rigidity can be addressed with flexibility training.

Rhythm and bodyweight supported treadmill training in physical therapy can assist with maintaining activity and improving ambulation. Frazzita et al showed a possible neuroprotective effect of intensive PT intervention, with two 4-week interventions resulting in improved UPDRS scores and reduced dose requirements for levodopa.14 Cued training may teach patients with PD to use external cues to facilitate movement, utilizing frontal cortical and cerebellar mechanisms instead of a defective basal ganglion circuit.15  Rhythmic auditory stimulation strategies utilizing music or metronome-based cues improve gait performance and modulate variability. Additionally, virtual reality training using visual cues has also been shown to improve gait.16 For patients with freezing of gait,  therapists  can provide training for patients and caregivers in strategies to improve step initiation. Large-amplitude based therapy programs can also improve impairment based outcome measures.17

Dietary interventions

Dietary counseling may be considered as well, depending on dietary history. Plant and fish-based diets are associated with lower PD severity.18 Coenzyme Q and fish oil supplements were found in one study to reduce rates of PD progression.

Subacute

Physical (PT) and occupational therapists (OT) assist with patient assessment and can provide training in the use of adaptive equipment. Ambulation safety may improve with the use of wheeled walkers with brakes. Walkers with a stabilizing base design, or with laser lights and portable metronomic devices that serve as cueing strategies to assist gait initiation and gait speed, can be helpful in selected patients. Occupational therapy assessments can identify how impairments lessen a patient’s safe performance of activities of daily living and inform recommendations for ADL equipment.

OT and speech language pathologist (SLP) interventions may be used to address visuo-spatial deficits, micrographia, and memory impairments.5 Amplitude-based voice programs focusing on vocal loudness promote improvements in speech intelligibility, hypophonia, and hoarseness.19 In addition, SLPs provide interventions for improving facial expression, oral-motor strengthening, and swallowing dysfunction.

Chronic/stable        

In advanced Parkinson disease, there is shortened duration of levodopa effect with more “wearing off”, motor fluctuations, and dyskinesias. The “off “ times may be addressed by giving more frequent medications, extended release formula, or adding adjunctive therapies as described above.2,5 Freezing and festination may become more problematic with time, and safety is often further reduced if there are concomitant declines in cognitive functions.

Other Interventions/Surgical Options

Deep Brain Stimulation (DBS), unilateral or bilateral, should be considered when patients have functional limitations due to “wearing off” of medications between doses and dyskinesias during times of peak medication concentrations despite pharmacologic optimization.4,5  Patients who have medication-responsive motor symptoms but cannot tolerate these side effects are candidates for DBS of the subthalamic nucleus or globus pallidus interna.5 MRI-guided focused ultrasound of the thalamus is also used for tremor.5 Patients excluded for DBS placement include those with atypical parkinsonism, unstable psychiatric disease, significant dementia, comorbidities precluding surgery, advanced age, or structural abnormalities interfering with lead placement.4

Pre-terminal or end of life care

Pre-terminal or end of life care may require evaluation and treatment for paranoid psychoses and visual hallucinations. As PD medications may contribute to these symptoms, re-assessment of such medications should be performed. With advanced disease, caring for patients with dementia and psychoses is particularly challenging. Caregiver stress should be identified and addressed, with considerations for supplemental caregiver assistance and support groups.

Gastrostomy tubes may be required with severe dysphagia if in line with the patient’s and family’s goals of care.

Coordination of care

A team approach including neurology, physiatry, speech-language pathology, physical therapy, occupational therapy and social work is recommended for continual reassessment of disease status and interventions. Interdisciplinary and inpatient rehabilitation reduces functional impairment in selected patients, despite the progressive disease process.20,21

Patient & family education

Patients and caregivers should receive training and education regarding medications, disease fluctuation, progression, exercise and rehabilitation strategies.

Measurement of Treatment Outcomes including those that are impairment-based, activity participation-based and environmentally based

TheMovement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) is used both clinically and to assess the impact of interventions in research studies. The PDQ-39 can be used to assess health-related quality of life.

Translation into Practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Identifying community exercise resources and providing and supervising ongoing home and/or community-based exercise programs are all essential components of PD disease management. Persons with PD who exercise at least 2.5 hours a week have been found to have a slower decline in quality of life.22 Long term exercise programs that include components of aerobic conditioning, strength training and flexibility are currently recommended.4 Cognitive training (puzzles, computer games) should also be encouraged.4

Cutting edge/emerging and unique concepts and practice

Glucocerebrosidase (GCase) genetic mutations in GBA1, the gene responsible for encoding this lysosomal enzyme, are important risk factors for PD.23 Ambroxol, a drug which increases GCase, has been recently shown in a small n trial to increase beta glucocerebrosidase enzyme protein levels in the cerebral spinal fluid.24 Gene replacement therapy of GBA1 is in early phase trials.

No pharmacologic treatments have been definitively shown to delay or prevent PD progression, however recent high intensity exercise suggests that such exercise may mitigate motor worsening in new-onset PD patients.5, 8, 20 Programs to target and train newly diagnosed PD patients in exercise strategies are in development.25

Gaps in the evidence-based knowledge

Non-motor symptoms (e.g. anosmia, constipation, and REM behavior disorder) in PD are frequent and may precede motor symptoms by years. The pathophysiology involved in underlying neuronal pathways and their relationship with motor symptoms, however, are not well understood and treatments are limited.2,26,27

Enteral dysfunction has been identified in PD and α-synuclein has been found in the GI tract on pathologic studies.28 In animal models of PD, vagus nerve resection can stop α-synuclein crossing the blood brain barrier, while bowel inflammation can trigger neuroinflammation and resultant dopaminergic loss. Thus, changes in gut microbiota or diet may be targeted as an intervention in the future.28

Though pain is common, well-designed evidence-based studies to treat pain (as well as other non-motor symptoms) are lacking.

References

  1. Fox SH, Katzenschlager R, Lim SY, et al. International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson’s disease. Mov Disord 2018;33:1248-66.
  2. Seppi K, Ray Chaudhuri K, Coelho M, et al. Update on treatments for nonmotor symptoms of Parkinson’s disease-an evidence-based medicine review. Mov Disord 2019;34:180-98.
  3. Lees AJ, Hardy J, Revesz T. Parkinson’s disease. Lancet 2009;373:2055-66.
  4. Zesiewicz TA. Parkinson Disease. Continuum (Minneap Minn) 2019;25:896-918.
  5. Armstrong MJ, Okun MS. Diagnosis and Treatment of Parkinson Disease: A Review. JAMA 2020;323:548-60.
  6. Lin YQ, Cui SS, Du JJ, et al. N1 and P1 Components Associate With Visuospatial-Executive and Language Functions in Normosmic Parkinson’s Disease: An Event-Related Potential Study. Front Aging Neurosci 2019;11:18.
  7. Kwok JYY, Kwan JCY, Auyeung M, et al. Effects of Mindfulness Yoga vs Stretching and Resistance Training Exercises on Anxiety and Depression for People With Parkinson Disease: A Randomized Clinical Trial. JAMA Neurol 2019;76:755-63
  8. Schenkman M, Moore CG, Kohrt WM, et al. Effect of High-Intensity Treadmill Exercise on Motor Symptoms in Patients With De Novo Parkinson Disease: A Phase 2 Randomized Clinical Trial. JAMA Neurol 2018;75:219-26.
  9. Corcos DM, Robichaud JA, David FJ, et al. A two-year randomized controlled trial of progressive resistance exercise for Parkinson’s disease. Mov Disord 2013;28:1230-40.
  10. Schenkman M, Hall DA, Baron AE, Schwartz RS, Mettler P, Kohrt WM. Exercise for people in early- or mid-stage Parkinson disease: a 16-month randomized controlled trial. Phys Ther 2012;92:1395-410.
  11. Ridgel AL, Vitek JL, Alberts JL. Forced, not voluntary, exercise improves motor function in Parkinson’s disease patients. Neurorehabil Neural Repair 2009;23:600-8.
  12. Mhatre PV, Vilares I, Stibb SM, et al. Wii Fit balance board playing improves balance and gait in Parkinson disease. PM R 2013;5:769-77.
  13. Zhu M, Zhang Y, Pan J, Fu C, Wang Y. Effect of simplified Tai Chi exercise on relieving symptoms of patients with mild to moderate Parkinson’s disease. J Sports Med Phys Fitness 2020;60:282-8.
  14. Frazzitta G, Maestri R, Bertotti G, et al. Intensive rehabilitation treatment in early Parkinson’s disease: a randomized pilot study with a 2-year follow-up. Neurorehabil Neural Repair 2015;29:123-31.
  15. Mak MK, Wong-Yu IS, Shen X, Chung CL. Long-term effects of exercise and physical therapy in people with Parkinson disease. Nat Rev Neurol 2017;13:689-703.
  16. Mirelman A, Maidan I, Herman T, Deutsch JE, Giladi N, Hausdorff JM. Virtual reality for gait training: can it induce motor learning to enhance complex walking and reduce fall risk in patients with Parkinson’s disease? J Gerontol A Biol Sci Med Sci 2011;66:234-40.
  17. Ebersbach G, Ebersbach A, Edler D, et al. Comparing exercise in Parkinson’s disease–the Berlin LSVT(R)BIG study. Mov Disord 2010;25:1902-8.
  18. Mischley LK, Lau RC, Bennett RD. Role of Diet and Nutritional Supplements in Parkinson’s Disease Progression. Oxid Med Cell Longev 2017;2017:6405278.
  19. McDonnell MN, Rischbieth B, Schammer TT, Seaforth C, Shaw AJ, Phillips AC. Lee Silverman Voice Treatment (LSVT)-BIG to improve motor function in people with Parkinson’s disease: a systematic review and meta-analysis. Clin Rehabil 2018;32:607-18.
  20. David FJ, Rafferty MR, Robichaud JA, et al. Progressive resistance exercise and Parkinson’s disease: a review of potential mechanisms. Parkinsons Dis 2012;2012:124527.
  21. Marciniak CM, Choo CM, Toledo SD, Semik PE, Aegesen AL. Do co-morbidities and cognition impact functional change and discharge needs in Parkinson disease? Am J Phys Med Rehabil 2011;90:272-80.
  22. Rafferty MR, Schmidt PN, Luo ST, et al. Regular Exercise, Quality of Life, and Mobility in Parkinson’s Disease: A Longitudinal Analysis of National Parkinson Foundation Quality Improvement Initiative Data. J Parkinsons Dis 2017;7:193-202.
  23. Sidransky E, Samaddar T, Tayebi N. Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset. Neurology 2009;73:1424-5, author reply 5-6.
  24. Mullin S, Smith L, Lee K, et al. Ambroxol for the Treatment of Patients With Parkinson Disease With and Without Glucocerebrosidase Gene Mutations: A Nonrandomized, Noncontrolled Trial. JAMA Neurol 2020.
  25. Rafferty MR, MacDonald J, Byskosh A, et al. Using Implementation Frameworks to Provide Proactive Physical Therapy for People With Parkinson Disease: Case Report. Phys Ther 2019;99:1644-55.
  26. Berg D, Postuma RB, Adler CH, et al. MDS research criteria for prodromal Parkinson’s disease. Mov Disord 2015;30:1600-11.
  27. Rees RN, Noyce AJ, Schrag A. The prodromes of Parkinson’s disease. Eur J Neurosci 2019;49:320-7.
  28. Zhu S, Jiang Y, Xu K, et al. The progress of gut microbiome research related to brain disorders. J Neuroinflammation 2020;17:25.

Original Version of the Topic

Christina Marciniak, MD, Rachel Kermen, MD, Priya Mhatre, MD. Idiopathic Parkinson Disease. 11/10/2011

Previous Version of the Topic

Christina Marciniak, MD, Rachel Kermen, MD, Priya Mhatre, MD. Idiopathic Parkinson Disease. 9/18/2015

Author Disclosures

Christina Marciniak, MD
Revance Therapeutics; My institution received funding for research in which I am participating, Principal investigator for NU site for this research study.

Kathryn Altonji, MD
Nothing to Disclose

Lauren Woo, MD
Nothing to Disclose

Rachel Kermen, MD
Nothing to Disclose

Priya Mhatre, MD
Nothing to Disclose