a multisystem neurodegenerative
a multisystem neurodegenerative
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Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease (AD) (Moore, Shpiner, & Luca, 2019). PD has been traditionally considered as a pure movement disorder secondary to focal degeneration of dopaminergic neurons in the substantia nigra, but, in recent years, the clinical phenotype has been better illuminated, showing that PD is a multisystem neurodegenerative disorder with motor and non-motor features. Among motor symptoms and signs, the cardinal ones (bradykinesia, rest tremor, and rigidity) are mainly the loss of dopaminergic neurons, but those involving posture, balance, and gait are largely secondary to degeneration of nondopaminergic pathways and significantly contribute to impairment and disability in advanced PD patients (Moore, Shpiner, & Luca, 2019). Nonmotor features result from multiple neurotransmitter deficiencies in the central and peripheral nervous system and include psychiatric such as: depression, apathy, hallucinations, and delusions. Autonomic includes constipation, orthostatic hypotension, and urinary and genital disturbances. Cognitive impairment such as: involvement of executive functions, memory, sleep disorders, olfactory dysfunction, and pain that together contribute to worsening the quality of life and patient’s disability (Moore, Shpiner, & Luca, 2019).
Cardinal motor features of Parkinson’s disease (PD) include bradykinesia, rest tremor, and rigidity, which appear in the early stages of the disease and largely depend on dopaminergic nigrostriatal denervation (Moore, Shpiner, & Luca, 2019). Intermediate and advanced PD stages are characterized by motor fluctuations and dyskinesia, which depend on complex mechanisms secondary to severe nigrostriatal loss and to the problems related to oral levodopa absorption, and motor and nonmotor symptoms and signs that are secondary to marked dopaminergic loss and multisystem neurodegeneration with damage to nondopaminergic pathways (Moore, Shpiner, & Luca, 2019). Nondopaminergic dysfunction results in motor problems, including posture, balance and gait disturbances, and fatigue, and nonmotor problems, encompassing depression, apathy, cognitive impairment, sleep disturbances, pain, and autonomic dysfunction. There are a number of symptomatic drugs for PD motor signs, but the pharmacological resources for nonmotor signs and symptoms are limited, and rehabilitation may contribute to their treatment (Moore, Shpiner, & Luca, 2019).
Pharmacological therapy is based on levodopa and dopamine agonists and is very successful in the early stages of the disease, when dopaminergic symptoms and signs are predominant and long term motor complications still have not developed, but other treatment strategies are necessary as time passes (Hajj, 2018). Long term levodopa-induced motor complications include motor fluctuations and dyskinesia and affect almost all PD patients at some point during the disease course, with relevant implications in global health status (Hajj, 2018). Despite various pharmacological approaches, as well as more invasive strategies including devices and functional neurosurgery, being available to manage such complications, many patients remain significantly disabled, and a fully satisfying management of motor complications is still an unmet need of PD therapy. Nonmotor symptoms and signs are integral to PD at onset and throughout the disease course, but to date their treatment is largely unsatisfactory (Hajj, 2018).
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