Parkinson’s disease
Keywords:
diagnosis, etiology, pathogenesis, Parkinson’s disease, treatmentAbstract
The prevalence of Parkinson’s disease is increasing due to improved diagnostic methods, extended life expectancy and the presence of more harmful substances in the environment. The disease is idiopathic, less often (3-5%) there are genetic factors. Pathophysiology is related to the complex relationships of aberrant α-synuclein protein aggregation, mitochondrial dysfunction, lysosomes and vesicular transport, synaptic transport disorders, and neuroinflammation. Pathophysiology is best explained by Braak's hypothesis. According to it, the disease begins with the appearance of Lewy bodies in the medulla oblongata and bulbus olfactorius or in the gastrointestinal tract and is spread by n. vagus to the brainstem. In addition to dopamine deficiency, there is a disorder of serotonin, acetylcholine and norepinephrine.
About 10 years before the onset of motor symptoms, nonmotor symptoms appear, which include RBD, olfactory disturbances, constipation, urinary disorders, orthostatic hypotension, daytime sleepiness, and depression. When more than 50% of the neurons in the substantia nigra are affected, motor symptoms also appear – tremor at rest, muscle rigidity and bradykinesia. As the disease progresses, periods of worsening of motor and non-motor symptoms (off periods) and dyskinesias occur. The course of the disease is heterogeneous, with slowly and rapidly progressive forms. The diagnosis is made clinically, and the effect of levodopa symptoms is assessed. Treatment of Parkinson's disease is symptomatic and begins when debilitating symptoms occur. Treatment is mainly with levodopa, dopamine agonists, MAO-B and COMT inhibitors. The early use of levodopa is controversial.
The glutamate NMDA receptor antagonist amantadine is used in patients with severe dyskinesia. Enteral infusion of levodopa/carbidopa suspension, levodopa/carbidopa gel with entacapone or deep brain stimulation of nucleus subthalamicus or globus pallidus internus may also be used. Unilateral focused ultrasound thalamotomy or deep brain stimulation of the thalamus may be used for predominantly tremor form. The treatment of non-motor symptoms does not differ from that of patients in the general population.
In conclusion, in recent years, the prevalence of Parkinson's disease has increased, but no progress has been made in the treatment of the disease.
References
Abdo, W.F., Borm, G.F., Munneke, M., Verbeek, M.M., Esselink, R.A., Bloem, B.R. Ten steps to identify atypical parkinsonism. J. Neurol. Neurosurg. Psychiatry, 2006, 77, 1367-1369.
Ahlskog, J.E., Muenter, M.D. Frequency of levodoparelated dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov. Disord., 2001, 16, 3, 448-458.
Antonini, A., Leta, V., Teo, J., Chaudhuri, K.R. Outcome of Parkinson’s disease patients affected by COVID-19. Mov. Disord., 2020, 35, 905-908.
Antonini, A., Poewe, W., Chaudhuri, K.R., Jech, R., Pickut, B., Pirtosek, Z., Szasz, J., Valldeoriola, F., Winkler, C., Bergmann, L., Yegin, A., Onuk, K., Barch, D., Odin, P., GLORIA study co-investigators. Levodopa-carbidopa intestinal gel in advanced Parkinson’s: Final results of the GLORIA registry. Parkinsonism Relat. Disord., 2017, 45, 13-20.
Armstrong, M.J., Okun, M.S. Diagnosis and treatment of Parkinson disease a review. JAMA, 2020, 323, 6, 548-560.
Berg, D., Postuma, R.B., Adler, C.H., Bloem, B.R., Chan, P., Dubois, B., Gasser, T., Goetz, C.G., Halliday, G., Joseph, L., Lang, A.E., Liepelt-Scarfone, I., Litvan, I., Marek, K., Obeso, J., Oertel, W., Olanow, C.W., Poewe, W., Stern, M., Deuschl, G., MDS research criteria for prodromal Parkinson’s disease. Mov. Disord., 2015, 30, 12, 1600-1611.
Bloem, B.R., Okun, M.S., Klein, C. Parkinson’s disease. Lancet, 2021, 397, 2284–303.
Bond, A.E., Shah, B.B., Huss, D.S., Dallapiazza, R.F., Warren, A., Harrison, M.B., Sperling, S.A., Wang, X.Q., Gwinn, R., Witt, J., Ro, S., Elias, W.J. Safety and efficacy of focused ultrasound thalamotomy for patients with medication-refractory, tremor-dominant Parkinson disease: a randomized clinical trial. JAMA Neurol., 2017, 74, 12, 1412-1418.
Braak, H., Del Tredici, K., Rüb, U., de Vos, R.A., Jansen Steur, E.N., Braak, E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol. Aging, 2003, 24, 2, 197-211.
Bratsos, S., Karponis, D., Saleh, S.N. Efficacyand safety of deep brain stimulation in the treatment of parkinson’s disease: a systematic review and metaanalysis of randomized controlled trials. Cureus, 2018, 10, 10, e3474.
Brundin, P., Nath, A., Beckham, J.D. Is COVID-19 a perfect storm for Parkinson’s disease? Trends Neurosci., 2020, 43, 931-933.
Calabrese, V., Santoro, A., Monti, D., Crupi, R., Di Paola, R., Latteri, S., Cuzzocrea, S., Zappia, M., Giordano, J., Calabrese, E.J., Franceschi, C. Aging and Parkinson’s disease: inflammaging, neuroinflammation and biological remodeling as key factors in pathogenesis. Free Radic. Biol. Med., 2018, 115, 80-91.
Cenci, M.A., Riggare, S., Pahwa, R., Eidelberg, D., Hauser, R.A. Dyskinesia Matters. Movement Disorders, 2019.
Chahine, L.M., Beach, T.G., Brumm, M.C., et al. In vivo distribution of alpha-synuclein in multiple tissues and biofluids in Parkinson disease. Neurology, 2020, 95, e1267-1284.
Chou, K.L., Stacy, M., Simuni, T., Miyasaki, J., Oertel, W.H., Sethi, K., Fernandez, H.H., Stocchi, F. The spectrum of “off” in Parkinson’s disease: what have we learned over 40 years? Parkinsonism Relat. Disord., 2018, 51, 9-16.
Cohen, M.E., Eichel, R., Steiner-Birmanns, B., Janah, A., Ioshpa, M., Bar-Shalom, R., Paul, J.J., Gaber, H., Skrahina, V., Bornstein, N.M., Yahalom, G. A case of probable Parkinson’s disease after SARS-CoV-2 infection. Lancet Neurol., 2020, 19, 804-805.
DePablo-Fernández, E., Lees, A.J., Holton, J.L., Warner, T.T. Prognosis and neuropathologic correlation of clinical subtypes of Parkinson disease. JAMA Neurol., 2019, 76, 4, 470-479.
Emre, M., Aarsland, D., Albanese, A., et al. Rivastigmine for dementia associated with Parkinson’s disease. N. Engl. J. Med., 2004, 351, 24, 2509-2518.
Espay, A.J., Lang, A.E. Common myths in the use of levodopa in Parkinson disease: when clinical trials misinform clinical practice. JAMA Neurol., 2017, 74, 6, 633-634.
Espay, A.J., Morgante, F., Merola, A., Fasano, A., Marsili, L., Fox, S.H., Bezard, E., Picconi, B., Calabresi, P., Lang, A.E. Levodopa-induced dyskinesia in Parkinson disease: current and evolving concepts. Ann. Neurol., 2018, 84, 6, 797-811.
Factor, S.A., McDonald, W.M., Goldstein, F.C. The role of neurotransmitters in the development of Parkinson’s disease–related psychosis. Eur. J. Neurol., 2017, 24, 10, 1244-1254.
Fasano, A., Antonini, A., Katzenschlager, R., Krack, P., Odin, P., Evans, A.H., Foltynie, T., Volkmann, J., Merello, M. Management of advanced therapies in Parkinson’s disease patients in times of humanitarian crisis: The COVID-19 experience. Movement Disorders Clinical Practice, 2020, 7, 4, 361-372.
Fearnley, J.M., Lees, A.J. Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain, 1991, 114, 5, 2283-2301.
Fox, S.H., Katzenschlager, R., Lim, S.Y., Barton, B., de Bie, R.M.A., Seppi, K., Coelho, M., Sampaio, C. Movement Disorder Society Evidence-Based Medicine Committee. 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, 8, 1248-1266.
Galbiati, A., Verga, L., Giora, E., Zucconi, M., Ferini-Strambi, L. The risk of neurodegeneration in REM sleep behavior disorder: a systematic review and meta-analysis of longitudinal studies. Sleep Med. Rev., 2019, 43, 37-46.
Garcia-Ruiz, P.J., Martinez Castrillo, J.C., Alonso-Canovas, A., Alonso-Canovas, A., Barcenas, A.H., Vela, L., Alonso, P.S., Mata, M., Gonzalez, N.O., Fernandez, I.M. Impulse control disorder in patients with Parkinson’s disease under dopamine agonist therapy: a multicentre study. J. Neurol. Neurosurg. Psychiatry, 2014, 85, 8, 840-844.
Giladi, N., Caraco, Y., Gurevich, T., Djaldetti, R. Pharmacokinetics and safety of ND0612L (levodopa/carbidopa for subcutaneous infusion): Results from a phase II study in moderate to severe Parkinson’s disease. [abstract]. Neurology, 2015, 84, Suppl. P1, 187.
Gray, R., Ives, N., Rick, C., Patel, S., Gray, A., Jenkinson, C., McIntosh, E., Wheatley, K., Williams, A., Clarke, C.E. PD Med Collaborative Group. Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors compared with levodopa as initial treatment for Parkinson’s disease (PD MED): a large, open-label, pragmatic randomised trial. Lancet, 2014, 384 (9949), 1196-1205.
Helmich, R.C., Bloem, B.R. The impact of the COVID-19 pandemic on Parkinson’s disease: hidden sorrows and emerging opportunities. J. Parkinsons Dis., 2020, 10, 351-354.
Horsager, J., Andersen, K.B., Knudsen, K., et al. Brainfirst versus body-first Parkinson’s disease: a multimodal imaging case-control study. Brain, 2020, 143, 3077-3088.
Howell, M.J., Schenck, C.H. Rapid eye movement sleep behavior disorder and neurodegenerative disease. JAMA Neurol., 2015, 72, 6, 707-712.
Huot, P., Sgambato-Faure, V., Fox, S.H., McCreary, A.C. Serotonergic Approaches in Parkinson’s Disease: Translational Perspectives, an Update. ACS Chem. Neurosci., 2017, 8, 5, 973-986.
Kalia, L.V., Lang, A.E. Parkinson’s disease. Lancet, 2015, 386, 896-912.
Kam, T.I., Mao, X., Park, H., et al. Poly(ADP-ribose) drives pathologic alpha-synuclein neurodegeneration in Parkinson’s disease. Science, 2018, 362, 8407.
Leodori, G., Belvisi, D., De Bartolo, M.I., Fabbrini, A., Costanzo, M., Vial, F., Conte, A., Hallett, M., Berardelli, A. Re-emergent Tremor in Parkinson’s Disease: The Role of the Motor Cortex. Movement Disorders, 2020, 35, 6,1002-1011.
LeWitt, P.A., Hauser, R.A., Pahwa, R., Isaacson, S.H., Fernandez, H.H., Lew, M., Saint-Hilaire, M., Pourcher, E., Lopez-Manzanares, L., Waters, C., Rudzínska, M., Sedkov, A., Batycky, R., Oh, C., PANPD Study Investigators. Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in patients with Parkinson’s disease: a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Neurol., 2019, 18, 2, 145-154.
Loens, S., Chorbadzhieva, E., Kleimann, A., Dressler, D., Schrader, C. Effects of levodopa/carbidopa intestinal gel versus oral levodopa/carbidopa on B vitamin levels and neuropathy. Brain Behav., 2017, 7, e00698.
Luquin, M.R., Kulisevsky, J., Martinez-Martin, P., Mir, P., Tolosa, E.S. Consensus on the definition of advanced Parkinson’s disease: a neurologists-based Delphi study (CEPA Study). Parkinsons Dis., 2017, 4047392.
Macleod, A.D., Taylor, K.S., Counsell, C.E. Mortality in Parkinson’s disease: a systematic review and metaanalysis. Mov. Disord., 2014, 29, 13, 1615-1622.
Maillet, A., Krack, P., Lhommée, E., Météreau, E., Klinger, H., Favre, E., Le Bars, D., Schmitt, E., Bichon, A., Pelissier, P., Fraix, V., Castrioto, A., Sgambato-Faure, V., Broussolle, E., Tremblay, L., Thobois, S. The prominent role of serotonergic degeneration in apathy, anxiety and depression in de novo Parkinson’s disease. Brain, 2016, 139, 9, 2486-2502.
Maini Rekdal, V., Bess, E.N., Bisanz, J.E., Turnbaugh, P.J., Balskus, E.P. Discovery and inhibition of an inter species gut bacterial pathway for Levodopa metabolism. Science, 2019, 364.
Merello, M., Bhatia, K.P., Obeso, J.A. SARS-CoV-2 and the risk of Parkinson’s disease: facts and fantasy. Lancet Neurol., 2021, 20, 94-95.
Merola, A., Romagnolo, A., Zibetti, M., Bernardini, A., Cocito, D., Lopiano, L. Peripheral neuropathy associated with levodopa-carbidopa intestinal infusion: A long-term prospective assessment. Eur. J. Neurol., 2016, 23, 501-509.
Morris, R., Martini, D.N., Madhyastha, T., Kelly, V.E., Grabowski, TJ., Nutt, J., Horak, F. Overview of the cholinergic contribution to gait, balance and falls in Parkinson’s disease. Parkinsonism Relat. Disord., 2019, 63, 20-30.
Nalls, M.A., Blauwendraat, C., Vallerga, C.L., et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet Neurol., 2019, 18, 1091-102.
Pahwa, R., Tanner, C.M., Hauser, R.A., Isaacson, S.H., Nausieda, P.A., Truong, D.D., Agarwal, P., Hull, K.L., Lyons, K.E., Johnson, R., Stempien, M.J. ADS-5102 (amantadine) extended-release capsules for levodopa-induced dyskinesia in Parkinson disease (EASE LID study): a randomized clinical trial. JAMA Neurol., 2017, 74, 8, 941-949.
Pennington, S., Snell, K., Lee, M., Walker, R. The cause of death in idiopathic Parkinson’s disease. Parkinsonism Relat. Disord., 2010, 16, 7, 434-437.
Postuma, R.B., Berg, D., Stern, M., Poewe, W., Olanow, C.W., Oertel, W., Obeso, J., Marek, K., Litvan, I., Lang, A.E., Halliday, G., Goetz, C.G., Gasser, T., Dubois, B., Chan, P., Bloem, B.R., Adler, C.H., Deuschl, G. MDS clinical diagnostic criteria for Parkinson’s disease: MDS-PD Clinical Diagnostic Criteria. Mov. Disord., 2015, 30, 1591-1601.
Schapira, A.H.V., Chaudhuri, K.R., Jenner, P. Nonmotor features of Parkinson disease. Nat. Rev. Neurosci., 2017, 18, 7, 435-450.
Senek, M., Nielsen, E.I., Nyholm, D. Levodopa- entacapone-carbidopa intestinal gel in Parkinson’s disease: A randomized crossover study. Mov. Disord., 2017, 32, 283-286.
Seppi, K., Ray Chaudhuri, K., Coelho, M., Fox, S.H., Katzenschlager, R., Lloret, S.P., Weintraub, D., Sampaio, C., the collaborators of the Parkinson’s Disease Update on Non-Motor Symptoms Study Group on behalf of the Movement Disorders Society Evidence-Based Medicine Committee. Update on treatments for nonmotor symptoms of Parkinson’s disease-an evidence-based medicine review. Mov. Disord., 2019, 34, 2, 180-198.
Stansley, B.J., Yamamoto, B.K. L-DOPA and brain serotonin system dysfunction. Toxics, 2015, 3, 75-88.
Stocchi, F., Rascol, O., Kieburtz, K., Poewe, W., Jankovic, J., Tolosa, E., Barone, P., Lang, A.E., Olanow, C.W. Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE-PD study. Ann. Neurol., 2010, 68, 1, 18-27.
Van Kessel, S.P., Frye, A.K., El-Gendy, A.O., Castejon, M., Keshavarzian, A., van Dijk, G., El Aidy, S. Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson’s disease. Nat. Commun., 2019, 10, 310.
Van Wamelen, D.J., Grigoriou, S., Chaudhuri, K.R., Odin, P. Continuous drug delivery aiming continuous dopaminergic stimulation in Parkinson’s disease. Journal of Parkinson’s Disease, 2018, 8, S65-S72.
Verschuur, C.V.M., Suwijn, S.R., Boel, J.A., et al. for the LEAP Study Group. Randomized delayed-start trial of levodopa in Parkinson’s disease. N. Engl. J. Med., 2019, 380, 315-324.
Williams-Gray, C.H., Mason, S.L., Evans, J.R., Foltynie, T., Brayne, C., Robbins, T.W., Barker, R.A. The CamPaIGN study of Parkinson’s disease: 10-year outlook in an incident population-based cohort. J.Neurol. Neurosurg. Psychiatry, 2013, 84, 11, 1258-1264.
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