Nonmotor Signs in Genetic Forms of Parkinson's Disease

Kasten, Meike; Marras, Connie; Klein, Christine

doi:10.1016/bs.irn.2017.05.030

Cited by 31 publications

(34 citation statements)

References 411 publications

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“…The benefit of symptom control through DBS surpasses that of optimal medical treatment in patients with motor fluctuations and dyskinesias, and it is a relatively safe treatment option for motor complications of idiopathic PD [1][2][3][4][5]. DBS is often performed in relatively early-onset PD, a population in which it has been estimated that at least 5-10% of cases are not sporadic, but may carry genetic mutations [6,7]. Genetic cases often are phenotypically different compared to sporadic patients, and this factor may influence clinical outcome [6,8].…”

Section: Introductionmentioning

confidence: 99%

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Deep brain stimulation for monogenic Parkinson’s disease: a systematic review

et al. 2019

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Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD) patients with motor fluctuations and dyskinesias. The key DBS efficacy studies were performed in PD patients with unknown genotypes; however, given the estimated monogenic mutation prevalence of approximately 5-10%, most commonly LRRK2, PRKN, PINK1 and SNCA, and risk-increasing genetic factors such as GBA, proper characterization is becoming increasingly relevant. We performed a systematic review of 46 studies that reported DBS effects in 221 genetic PD patients. The results suggest that monogenic PD patients have variable DBS benefit depending on the mutated gene. Outcome appears excellent in patients with the most common LRRK2 mutation, p.G2019S, and good in patients with PRKN mutations but poor in patients with the more rare LRRK2 p.R1441G mutation. The overall benefit of DBS in SNCA, GBA and LRRK2 p.T2031S mutations may be compromised due to rapid progression of cognitive and neuropsychiatric symptoms. In the presence of other mutations, the motor changes in DBS-treated monogenic PD patients appear comparable to those of the general PD population.

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Section: Introductionmentioning

confidence: 99%

“…DBS is often performed in relatively early-onset PD, a population in which it has been estimated that at least 5-10% of cases are not sporadic, but may carry genetic mutations [6,7]. Genetic cases often are phenotypically different compared to sporadic patients, and this factor may influence clinical outcome [6,8].…”

Section: Introductionmentioning

confidence: 99%

Deep brain stimulation for monogenic Parkinson’s disease: a systematic review

et al. 2019

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“…Gene multiplication seems to be more common in the European and Asian populations (Kasten and Klein, 2013). Patients carrying SNCA mutations often experience bradykinesia and rigidity, while only about 30% of mutation carriers report resting tremor and postural instability (Kasten et al, 2017).…”

Section: Park1/park4-sncamentioning

confidence: 99%

“…As for the NMS features of SNCA monogenic PD, cognitive decline is the most common symptom, followed by depression, autonomic dysfunction, and other psychotic manifestations (Kasten et al, 2017;Chen et al, 2020). The longitudinal clinical assessments at a 2-year follow-up study conducted by Papadimitriou et al (2016) have shown that the prominent NMS includes olfactory, autonomic, and cognitive dysfunctions in A53T symptomatic and asymptomatic carriers.…”

Section: Park1/park4-sncamentioning

confidence: 99%

Profiling Non-motor Symptoms in Monogenic Parkinson’s Disease

Liu

2020

Front. Aging Neurosci.

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Parkinson's disease (PD) is the second most common neurodegenerative disease in the elder population, pathologically characterized by the progressive loss of dopaminergic neurons in the substantia nigra. While the precise mechanisms underlying the pathogenesis of PD remain unknown, various genetic factors have been proved to be associated with PD. To date, at least 23 loci and 19 disease-causing genes for PD have been identified. Although monogenic (often familial) cases account for less than 5% of all PD patients, exploring the phenotypes of monogenic PD can help us understand the disease pathogenesis and progression. Primary motor symptoms are important for PD diagnosis but only detectable at a relatively late stage. Despite typical motor symptoms, various non-motor symptoms (NMS) including sensory complaints, mental disorders, autonomic dysfunction, and sleep disturbances also have negative impacts on the quality of life in PD patients and pose major challenges for disease management. NMS is common in all stages of the PD course. NMS can occur long before the onset of PD motor symptoms or can present in the middle or late stage of the disease accompanied by motor symptoms. Therefore, the profiling and characterization of NMS in monogenic PD may help the diagnosis and differential diagnosis of PD, which thereby can execute early intervention to delay the disease progression. In this review, we summarize the characteristics, clinical phenotypes, especially the NMS of monogenic PD patients carrying mutations of SNCA, LRRK2, VPS35, Parkin, PINK1, DJ-1, and GBA. The clinical implications of this linkage between NMS and PD-related genes are also discussed.

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“…Genetic models often involve mice depleted from dopaminergic synapse-related genes. Although several genes have been related to the development of nonmotor signs of PD in humans (e.g., SNCA, LRRK2, VPS35, and Parkin), only a few studies have explored the influence of these mutations on depressive-like behavior in mice [ 62 ].…”

Section: Animal Models Of Pdmentioning

confidence: 99%

Depression in Parkinson’s Disease: The Contribution from Animal Studies

Fontoura

Baptista

Pedroso

et al. 2017

Parkinson's Disease

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Besides being better known for causing motor impairments, Parkinson's disease (PD) can also cause many nonmotor symptoms, like depression and anxiety, which can cause significant loss of life quality and may not respond to regular drugs treatment. In this review, we discuss the depression in PD, based on data from studies in humans and rodents. Depression frequency seems higher in PD patients than in general population, despite high variation in data due to diagnosis disparities. Development of depression in PD seems more likely to be caused by the nigrostriatal pathway degeneration than as a consequence of the awareness of disease prognostic, and it seems to be related to dopaminergic, noradrenergic, and serotoninergic synapses deficits. The dopaminergic role could be more significant, since it can modulate the release of the others, and its depletion is progressive, due to the degenerative feature of PD. Highly regarded in major depression, serotonin can be depleted in rats after nigrostriatal damage, but data from human patients are more conflicting. Animal studies can help in understanding the neurobiological mechanisms of depression in PD and the pursuit for more effective drugs for its treatment, but they lack the complexity of the disease progression, especially the nondopaminergic degeneration.

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Nonmotor Signs in Genetic Forms of Parkinson's Disease

Cited by 31 publications

References 411 publications

Deep brain stimulation for monogenic Parkinson’s disease: a systematic review

Deep brain stimulation for monogenic Parkinson’s disease: a systematic review

Profiling Non-motor Symptoms in Monogenic Parkinson’s Disease

Depression in Parkinson’s Disease: The Contribution from Animal Studies

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