By Colin Farrell B.Sc.
Parkinson’s Disease (PD) is a neurodegenerative disease with symptomatic features including impaired motor and autonomic function, cognitive impairment, and psychiatric disturbances (Cronin-Golomb, 2013). Juvenile-onset (occuring before age 20) and early-onset (occuring before age 40) are variants of the condition, which in its typical form classically occurs around age 60. Increasing age is the biggest risk factor for development of PD (Grosset, Fernandez, & Okun, 2009). It is the second most common neurodegenerative disease after Alzheimer’s Disease (Simuni & Pahwa, 2009). The leading cause of death in PD is pneumonia, frequently due to impairment of the swallowing muscles (Walker, 2013). Worldwide prevalence of PS is generally accepted as 200 cases per 100,000 individuals, with men 1.5 times more likely than women to develop it (Chaudhuri, Clough, & Sethi, 2011). The number of individuals with PD in the Republic of Ireland is slightly lower than average and has been estimated at approximately 7,000 (Gustavsson et al., 2011).
Clinical features of PD include physical symptoms such as tremor, which most often occurs in the extremities but can also affect the lips, tongue, and face (Tuite, Thomas, & Reukert, 2009); and progressively slowed/reduced movement (Ling, Massey, Lees, Brown, & Day, 2012). The trademark Parkinsonian tremor or “resting tremor” occurs during muscle relaxation (Nistico et al., 2011); posture, balance, and gait are also facets of motor ability which are impaired (Mille et al. 2012). Patients have sometimes reported an internal tremor sensation, which can cause restlessness, discomfort, and distress (Friedman, 2009). Muscle rigidity is a common feature of PD, with increased tone and decreased strength resulting in likelihood of falls and slower walking speed (Paul, Canning, Sherrington, & Fung, 2012). Such motor symptoms often appear unilaterally at onset of the disease and usually progress to affect both sides of the body (Tuite, Thomas, & Reukert, 2009). Nonmotor symptoms which occur early in disease manifestation include olfactory deficit, Rapid Eye Movement sleep disorders, and erectile dysfunction; these are often manifest before diagnosis and have been identified as potential early indicators of PD (Chaudhuri & Naidu, 2008).
Cognitive impairment is increasingly recognised as a symptom of PD (Archibald, Hutton, Clarke, Mosimann, & Burn, 2013); with 1 in every 4-5 patients suffering from dementia to some extent (Weiner, Shulman & Lang, 2006). Mild cognitive impairment is also prevalent, and is associated with more accompanying neuropsychiatric symptoms (Maranon, Amayra, Uterga & Gomez-Esteban, 2011). Such symptoms include sleep disturbances, anxiety, dysphoria/depression, delusions, and hallucinations (Leroi, Pantula, McDonald, & Harbishettar, 2012).
PD is caused by the loss of dopiminergenic neurons in the area of the midbrain known as the substantia nigra; while several genes have been identified in the pathogenesis of this neuronal loss, specific understanding of disease activation and progression are not well defined (Filatova, Alieva, Shadrina, & Slominsky, 2012). Also implicated in PD is the dysfunction and accumulation of alpha-synuclein proteins in the brainstem and basal ganglia to the cerebral cortex (Shoji et al., 2000). Alpha-synuclein aggregates to form what are known as Lewy Bodies, cytotoxic materials which cause cell death in surrounding cortical areas (Wakabayashi et al., 2013).
In terms of neuropharmacological treatment for PD, the biochemical Levodopa is still the clinicians’ standard in reduction and management of parkinsonian symptoms (Kääriäinen, et al., 2012). This occurs through restoration of extracellular dopamine levels in the PD affected cortical areas (Navailles, Carta, Guthrie, & De Deurwaerdère, 2011); however, a complication arising from this treatment is eventual persistence of involuntary movements due to neural plasticity in these areas (Iravani, McCreary, & Jenner, 2012). In addition, the drug rasagiline has been found to have rapid and significant efficacy in reduction of motor symptoms – particularly in problems with slowness of movement (Silver & Buck, 2011; Zambito Marsala et al., 2013). Treatment utilising both drugs simultaneously has also shown positive results (Zhang et al., 2013).
As symptoms often present at an advanced stage of disease progression in PD, this inhibits the efficacy of treatments; therefore further exploration of its pathogenesis is a priority for research in the near future (Khaindrava et al, 2011). A solution to this issue may lie in combining neuroimaging techniques such as transcranial sonography and scintigraphy (Behnke et al., 2013). Other recent advances in early diagnosis have been achieved through identification of blood based biomarkers using identification of specific proteins and autoantibodies (Pagan, 2012).
Archibald, N. K., Hutton, S. B., Clarke, M. P., Mosimann, U. P., & Burn, D. J. (2013). Visual exploration in Parkinson’s disease and Parkinson’s disease dementia. Brain: A Journal Of Neurology, 136(3), 739-750.
Behnke, S., Hellwig, D., Bürmann, J., Runkel, A., Farmakis, G., Kirsch, C. M., & … Spiegel, J. (2013). Evaluation of transcranial sonographic findings and mibg cardiac scintigraphy in the diagnosis of idiopathic parkinson’s disease. Parkinsonism & Related Disorders, doi:10.1016/j.parkreldis.2013.06.019
Chaudhuri, K.R., & Naidu, Y. (2008). Early Parkinson’s disease and non-motor issues. Journal of Neurology, 255, 33-38. doi:10.1007/s00415-008-5006-1
Chaudhuri, K.R., Clough, C.G., & Sethi, K.D. (2011). Fast Facts : Parkinson’s Disease (3rd Edition). Oxford, GBR: Health Press Limited.
Cronin-Golomb, A. (2013). Emergence of nonmotor symptoms as the focus of research and treatment of Parkinson’s disease: Introduction to the special section on nonmotor dysfunctions in Parkinson’s disease. Behavioral Neuroscience, 127(2), 135-138. doi:10.1037/a0032142
Filatova, E. E., Alieva, A. A., Shadrina, M. M., & Slominsky, P. P. (2012). MicroRNAs: Possible role in pathogenesis of Parkinson’s disease. Biochemistry (00062979), 77(8), 813-819. doi:10.1134/S0006297912080020
Friedman, J. H. (2009). Non-motor Movement Disorders: Internal Tremor. Medicine & Health Rhode Island, 92(8), 262.
Grosset, D., Fernandez, H., & Okun, M. (2009). Parkinson’s Disease : Clinican’s Desk Reference. London, GBR: CRC Press.
Gustavsson, A., Svensson, M., Jacobi, F., Allgulander, C., Alonso, J., Beghi, E., & … Lieb, R. (2011). Cost of disorders of the brain in Europe 2010. European Neuropsychopharmacology, 21(10), 718-779. doi:10.1016/j.euroneuro.2011.08.008
Iravani, M. M., McCreary, A. C., & Jenner, P. P. (2012). Striatal plasticity in Parkinson’s disease and L-DOPA induced dyskinesia. Parkinsonism & Related Disorders, 18(Suppl 1), S123-S125. doi:10.1016/S1353-8020(11)70038-4
Kääriäinen, T. M., Käenmäki, M., Forsberg, M. M., Oinas, N., Tammimäki, A., & Männistö, P. T. (2012). Unpredictable Rotational Responses to L-dopa in the Rat Model of Parkinson’s Disease: the Role of L-dopa Pharmacokinetics and Striatal Dopamine Depletion. Basic & Clinical Pharmacology & Toxicology, 110(2), 162-170. doi:10.1111/j.1742-7843.2011.00782.x
Khaindrava, V. G., Kozina, E. A., Kudrin, V. S., Kucheryanu, V. G., Klodt, P. D., Narkevich, V. B., & … Ugrumov, M. V. (2011). Experimental modeling of preclinical and clinical stages of Parkinson’s disease. Bulletin Of Experimental Biology & Medicine, 150(5), 566-569. doi:10.1007/s10517-011-1191-5
Leroi, I., Pantula, H., McDonald, K., & Harbishettar, V. (2012). Neuropsychiatric Symptoms in Parkinson’s Disease with Mild Cognitive Impairment and Dementia. Parkinson’s Disease (20420080), 1-10. doi:10.1155/2012/308097
Ling, H., Massey, L. A., Lees, A. J., Brown, P., & Day, B. L. (2012). Hypokinesia without decrement distinguishes progressive supranuclear palsy from Parkinson’s disease. Brain: A Journal Of Neurology, 135(4), 1141-1153.
Marañon, D., Amayra, I., Uterga, J., & Gómez-Esteban, J. (2011). Deterioro neuropsicológico en la enfermedad de Parkinson sin demencia. (Spanish). Psicothema, 23(4), 732-737.
Mille, M., Creath, R. A., Prettyman, M. G., Hilliard, M., Martinez, K. M., MacKinnon, C. D., & Rogers, M. W. (2012). Posture and Locomotion Coupling: A Target for Rehabilitation Interventions in Persons with Parkinson’s Disease. Parkinson’s Disease (20420080), 1-10. doi:10.1155/2012/754186
Navailles, S., Carta, M., Guthrie, M., & De Deurwaerdère, P. (2011). L-DOPA and Serotonergic Neurons: Functional Implication and Therapeutic Perspectives in Parkinson’s Disease. Central Nervous System Agents in Medicinal Chemistry, 11(4), 305-320.
Nisticò, R. R., Pirritano, D. D., Salsone, M. M., Novellino, F. F., Del Giudice, F. F., Morelli, M. M., & … Quattrone, A. A. (2011). Synchronous pattern distinguishes resting tremor associated with essential tremor from rest tremor of Parkinson’s disease. Parkinsonism & Related Disorders, 17(1), 30-33. doi:10.1016/j.parkreldis.2010.10.006
Pagán, F. L. (2012). Improving Outcomes Through Early Diagnosis of Parkinson’s Disease. American Journal Of Managed Care, 18, S176-S182.
Paul, S. S., Canning, C. G., Sherrington, C. C., & Fung, V. C. (2012). Reduced muscle strength is the major determinant of reduced leg muscle power in Parkinson’s disease. Parkinsonism & Related Disorders, 18(8), 974-977. doi:10.1016/j.parkreldis.2012.05.007
Shoji, M., Harigaya, Y., Sasaki, A., Ueda, K., Ishiguro, K., Matsubara, E.,…& Hirai, S. (2000). Accumulation of NACP/alpha-synuclein in lewy body disease and multiple system atrophy. Journal of neurology, neurosurgery, and psychiatry, 68(5), 605-608.
Silver, D. E., & Buck, P. O. (2011). Determining the Efficacy of Rasagiline in Reducing Bradykinesia Among Parkinson’s Disease Patients: A Review. International Journal Of Neuroscience, 121(9), 485-489. doi:10.3109/00207454.2011.582240
Simuni, T., & Pahwa, R. (2009). Parkinson’s Disease. Cary, NC: Oxford University Press.
Tuite, P., Thomas, C., & Reukert, L. (2009). Parkinson’s Disease : A Guide to Patient Care. New York, NY: Springer Publishing Company.
Wakabayashi, K., Tanji, K., Odagiri, S., Miki, Y., Mori, F., & Takahashi, H. (2013). The Lewy body in Parkinson’s disease and related neurodegenerative disorders. Molecular Neurobiology, 47(2), 495-508. doi:10.1007/s12035-012-8280-y
Walker, R. (2013). Palliative care and end-of-life planning in Parkinson’s disease. Journal Of Neural Transmission, 120(4), 635-638. doi:10.1007/s00702-013-0967-3
Weiner, W.J., Shulman, L.M., & Lang, A.E. (2006). Parkinson’s Disease : A Complete Guide for Patients and Families (2nd Editon). Baltimore, MD: John Hopkins University Press.
Zambito Marsala, S., Vitaliani, R., Volpe, D., Capozzoli, F., Baroni, L., Belgrado, E., & … Antonini, A. (2013). Rapid onset of efficacy of rasagiline in early parkinson’s disease. Neurological Sciences, doi:10.1007/s10072-013-1437-2
Zhang, L., Zhang, Z., Chen, Y., Qin, X., Zhou, H., Zhang, C., & … Li, J. (2013). Efficacy and safety of rasagiline as an adjunct to levodopa treatment in Chinese patients with Parkinson’s disease: A randomized, double-blind, parallel-controlled, multi-centre trial. International Journal Of Neuropsychopharmacology, 16(7), 1529-1537.