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Signs and symptoms

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Main article: Signs and symptoms of Parkinson's disease

The defining symptoms affect the motor system and include tremor, bradykinesia, rigidity, and postural instability. Other symptoms may affect the autonomic or sensory nervous system, mood, behavior, sleep patterns, and cognition.[1]

Non-motor symptoms may precede the onset of motor symptoms by up to 20 years. These include constipation, anosmia, mood disorders, and REM sleep behavior disorder among others.[2] In general, motor symptoms such as postural instability and gait abnormalities tend to appear as the disease progresses.[3]

Motor

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Features of Parkinsonian gait (more obvious in the side view)[4]
See also: Parkinsonism

Four motor symptoms are considered as cardinal signs in PD: tremor, bradykinesia, rigidity, and postural instability, collectively known as parkinsonism.[1] However, other motor-associated symptoms are common.

Tremor is the most common presenting sign and may appear at rest as well as during intentional movement with a frequency between 4–6 hertz (cycles per second).[5] PD tremor tends to occur in the hands, but can affect other parts of the body, such as legs, arms, tongue, or lips, as well. It is often described as "pill-rolling", the tendency of the index finger and thumb to touch and perform a circular movement that reminds of the early pharmaceutical technique of manually making pills. Despite it being the most noticeable sign, tremor is present in only about 70–90 percent of cases.[6][5]

Bradykinesia is often considered the most important feature of Parkinson's disease and is also present in atypical parkinsonism. It describes difficulties in motor planning, beginning, and executing, resulting in overall slowed movement with reduced amplitude which affects sequential and simultaneous tasks.[7] Hence, it interferes with daily activities such as dressing, feeding and bathing.[8] Facial muscles involved in bradykinesia lead to the characteristic reduced facial expression known as "masked face" or hypomimia.[9]

Rigidity, also referred to as rigor or "stiffness", is the increased resistance during passive mobilization of a limb affecting up to 89 percent of cases.[10] It usually occurs after onset of tremor and bradykinesia on one or both sides of the body and can lead to muscle or joint pain as the disease progresses.[11] As of 2024, it remains unclear whether rigidity is caused by a distinct biomechanical process or if it is the manifestation of another cardinal sign of PD.[12]

Postural instability (PI) is typical in the later stages of the disease, leading to impaired balance and falls, and secondarily to bone fractures, thus, reduced mobility and quality of life. PI is absent in the initial stages and usually occurs 10–15 years after first diagnosis. Within the first three years after disease onset, PI may indicate atypical parkinsonism.[13] Together with bradykinesia and rigidity, it is responsible for the typical gait characterized by short shuffling steps and forward-flexed posture.[14]

Other common motor signs include a slurred and quiet voice, and handwriting that progressively becomes smaller. This latter may occur prior to other typical symptoms, but the exact neurobiological mechanism, and therefore possible connections with other symptoms, remains unknown.[15]

Autonomic

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Alterations in the autonomic nervous system, known as dysautonomia, are associated with a variety of symptoms such as gastrointestinal dysfunction, orthostatic hypotension, excessive sweating, or urinary incontinence.[16] Gastrointestinal issues include constipation, impaired stomach emptying, immoderate production of saliva, and swallowing difficulty (prevalence up to 82 percent). Complications resulting from dysphagia include dehydration, malnutrition, weight loss, and aspiration pneumonia.[17] All gastrointestinal features can be severe enough to cause discomfort, endanger health,[18] and complicate disease management.[19] Despite being related to each other, the exact mechanism of these symptoms remains unknown.[20]

Orthostatic hypotension is the sustained drop of blood pressure by at least 20 mmHg systolic or 10 mmHg diastolic within the first three minutes after raising to an upright position that can be seen in 30–50 percent of cases. Low blood pressure can impair the perfusion of organs situated above the heart, particularly the brain, resulting in lightheadedness. This can eventually lead to fainting and is associated with higher morbidity and mortality.[21] Other autonomic-related symptoms include excessive sweating, urinary incontinence, and sexual dysfunction.[16]

Neuropsychiatric

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Neuropsychiatric symptoms (NPS) are common and range from mild disturbances to severe impairment, comprising abnormalities in cognition, mood, behavior, or thought which can interfere with daily activities, reduce quality of life, and increase the risk for admission to a nursing home. Some of them, such as depression and anxiety, are known to precede characteristic motor signs by up to several years and may herald the development of PD, while most of them worsen as the disease progresses.[22] Research indicates that patients with more severe motor symptoms are at higher risk for any NPS. Conversely, NPS can worsen PD.[23][24]

Depression is the most common NPS and occurs in nearly half of all patients. It features low mood and lack of pleasure and is more prevalent in women. The diagnosis can be challenging since some symptoms of depression such as psychomotor retardation, memory problems, or altered appetite, share similarities with psychiatric signs caused by PD.[23] It may result in suicidal ideation which is more prevalent in PD. Nonetheless, suicidal attempts themselves are lower than in the general population.[25]

Apathy is characterized by emotional indifference and arises in about 46 percent of cases. Diagnosis is difficult, as it may become indistinct from symptoms of depression.[23]

Anxiety disorders develop in around 43 percent of cases.[23] The most common are panic disorder, generalized anxiety disorder, and social anxiety disorder.[22] Anxiety is known to cause deterioration in the symptoms of PD.[24]

Parkinson's disease psychosis (PDP) is present in around 20 percent of cases[26] and comprises hallucinations, illusions and delusions. It is associated with dopaminergic drugs used to treat the motor symptoms, higher morbidity, mortality, a decrease in health-promoting behaviors, and longer nursing home stays. Additionally, it correlates with depression and may herald onset of dementia in advanced stages. Unlike other psychotic forms, PDP typically presents with a clear sensorium.[27] It might overlap with other psychiatric symptoms, making the diagnosis challenging.[28]

Impulse-control disorders (ICD) can be seen in approximately 19 percent of all patients[23] and, in the context of PD, are grouped along with compulsive behavior and dopamine dysregulation syndrome (DDS) within the broader spectrum of impulsive and compulsive behaviors (ICB). They are characterized by impulsivity and difficulty to control impulsive urges and are positively correlated with the use of dopamine agonists.[29]

Sensory

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Transformation of the sensory nervous system can lead to changes in sensation that include an impaired sense of smell, disturbed vision, pain, and paresthesia.[30] Problems with visuospatial function may arise and lead to difficulties in facial recognition and perception of the orientation of drawn lines.[31]

Peripheral neuropathy is known to be present in up to 55 percent of PD patients. While it is responsible for most of paresthesia and pain in PD, its role in postural instability and motor impairment is poorly understood.[30]

Cognitive

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Cognitive disturbances can occur in early stages or before diagnosis, and increase in prevalence and severity with duration of the disease. Ranging from mild cognitive impairment to severe Parkinson's disease dementia, they feature executive dysfunction, slowed cognitive processing speed, and disrupted perception and estimation of time.[32]

Sleep

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Sleep disorders are common in PD and affect about two thirds of all patients.[33] They comprise insomnia, excessive daytime sleepiness (EDS), restless legs syndrome (RLS), REM sleep behavior disorder (RBD), and sleep-disordered breathing (SDB), many of which can be worsened by medication. RBD may begin years prior to the initial motor symptoms. Individual presentation of symptoms vary, although most of people affected by PD show an altered circadian rhythm at some point of disease progression.[34][35]

Other

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PD is associated with a variety of skin disorders that include melanoma, seborrheic dermatitis, bullous pemphigoid, and rosacea.[36] Seborrheic dermatitis is recognized as a premotor feature that indicates dysautonomia and demonstrates that PD can be detected not only by changes of nervous tissue, but tissue abnormalities outside the nervous system as well.[37]

References

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  2. ^ Leite Silva AB, Gonçalves de Oliveira RW, Diógenes GP, de Castro Aguiar MF, Sallem CC, Lima MP, de Albuquerque Filho LB, Peixoto de Medeiros SD, Penido de Mendonça LL, de Santiago Filho PC, Nones DP, da Silva Cardoso PM, Ribas MZ, Galvão SL, Gomes GF, Bezerra de Menezes AR, Dos Santos NL, Mororó VM, Duarte FS, Dos Santos JC (February 2023). "Premotor, nonmotor and motor symptoms of Parkinson's Disease: A new clinical state of the art". Ageing Research Reviews. 84: 101834. doi:10.1016/j.arr.2022.101834. PMID 36581178.
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  21. ^ Palma JA, Kaufmann H (February 2020). "Orthostatic Hypotension in Parkinson Disease". Clinics in Geriatric Medicine. 36 (1): 53–67. doi:10.1016/j.cger.2019.09.002. PMC 7029426. PMID 31733702.
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  23. ^ a b c d e Macías-García P, Rashid-López R, Cruz-Gómez ÁJ, Lozano-Soto E, Sanmartino F, Espinosa-Rosso R, González-Rosa JJ (9 May 2022). Aasly J (ed.). "Neuropsychiatric Symptoms in Clinically Defined Parkinson's Disease: An Updated Review of Literature". Behavioural Neurology. 2022: 1213393. doi:10.1155/2022/1213393. PMC 9110237. PMID 35586201.
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  25. ^ Weintraub D, Mamikonyan E (September 2019). "The Neuropsychiatry of Parkinson Disease: A Perfect Storm". The American Journal of Geriatric Psychiatry. 27 (9): 998–1018. doi:10.1016/j.jagp.2019.03.002. PMC 7015280. PMID 31006550.
  26. ^ Chendo I, Silva C, Duarte GS, Prada L, Voon V, Ferreira JJ (21 January 2022). "Frequency and Characteristics of Psychosis in Parkinson's Disease: A Systematic Review and Meta-Analysis". Journal of Parkinson's Disease. 12 (1): 85–94. doi:10.3233/JPD-212930. PMID 34806620.
  27. ^ Zhang S, Ma Y (September 2022). "Emerging role of psychosis in Parkinson's disease: From clinical relevance to molecular mechanisms". World Journal of Psychiatry. 12 (9): 1127–1140. doi:10.5498/wjp.v12.i9.1127. PMC 9521528. PMID 36186499.
  28. ^ Pahwa R, Isaacson SH, Small GW, Torres-Yaghi Y, Pagan F, Sabbagh M (December 2022). "Screening, Diagnosis, and Management of Parkinson's Disease Psychosis: Recommendations From an Expert Panel". Neurology and Therapy. 11 (4): 1571–1582. doi:10.1007/s40120-022-00388-y. PMC 9362468. PMID 35906500.
  29. ^ De Wit LE, Wilting I, Souverein PC, van der Pol P, Egberts TC (May 2022). "Impulse control disorders associated with dopaminergic drugs: A disproportionality analysis using vigibase". European Neuropsychopharmacology. 58: 30–38. doi:10.1016/j.euroneuro.2022.01.113. PMID 35189453.
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  31. ^ França M, Parada Lima J, Oliveira A, Rosas MJ, Vicente SG, Sousa C (September 2023). "Visuospatial memory profile of patients with Parkinson's disease". Applied Neuropsychology. Adult: 1–9. doi:10.1080/23279095.2023.2256918. hdl:10216/141606. PMID 37695259.
  32. ^ Gonzalez-Latapi P, Bayram E, Litvan I, Marras C (May 2021). "Cognitive Impairment in Parkinson's Disease: Epidemiology, Clinical Profile, Protective and Risk Factors". Behavioral Sciences. 11 (5): 74. doi:10.3390/bs11050074. PMC 8152515. PMID 34068064.
  33. ^ "Parkinson's Disease Sleep Problems". Cleveland Clinic. Retrieved 1 May 2024.
  34. ^ Bollu PC, Sahota P (2017). "Sleep and Parkinson Disease". Missouri Medicine. 114 (5): 381–386. PMC 6140184. PMID 30228640.
  35. ^ Dodet P, Houot M, Leu-Semenescu S, Corvol JC, Lehéricy S, Mangone G, Vidailhet M, Roze E, Arnulf I (February 2024). "Sleep disorders in Parkinson's disease, an early and multiple problem". npj Parkinson's Disease. 10 (1): 46. doi:10.1038/s41531-024-00642-0. PMC 10904863. PMID 38424131.
  36. ^ Niemann N, Billnitzer A, Jankovic J (January 2021). "Parkinson's disease and skin". Parkinsonism & Related Disorders. 82: 61–76. doi:10.1016/j.parkreldis.2020.11.017. PMID 33248395.
  37. ^ Almikhlafi MA (January 2024). "A review of the gastrointestinal, olfactory, and skin abnormalities in patients with Parkinson's disease". Neurosciences. 29 (1): 4–9. doi:10.17712/nsj.2024.1.20230062 (inactive 2 May 2024). PMC 10827020. PMID 38195133.{{cite journal}}: CS1 maint: DOI inactive as of May 2024 (link)

Journal articles

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  • Bloem BR, Okun MS, Klein C (June 2021). "Parkinson's disease". The Lancet. 397 (10291): 2284–2303. PMID 33848468.


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