scholarly journals LRRKing up the right trees? On figuring out the effects of mutant LRRK2 and other Parkinson's disease-related genes

Basal Ganglia ◽  
2013 ◽  
Vol 3 (2) ◽  
pp. 73-76 ◽  
Author(s):  
Heinz Steiner
Author(s):  
Hector Riquelme-Heras

Background: Parkinson's disease was described for the first time by James Parkinson in 1817 in the trial "Shaking Palsy," and thus there is also evidence of this disease in the Indian medical system 4500 years ago, for the diagnosis and its management with Mucuna pruriens.Years later, it was subsequently determined to contain levodopa. Two types of manifestations of Parkinson's disease are currently known, such as motor and non-motor, the first being the one that usually leads to diagnosis. Success in this will depend on the skill of the primary care physician, the ability to recognize the first symptoms by the patient, and the health systems in the management of care for the timely referral. This work shows the comprehensive management of a patient who arrives at Primary Care services, presenting vague and specific symptoms. These symptoms were treated with medications or remedies in order to calm the condition temporarily. It is convenient to call the specific symptoms such as headache, nausea, pain, dizziness, tiredness and weakness, poor motivation, sadness, easy crying, and sleep disturbances; A large percentage go to their health centers for presenting motor alterations, many times identified by their relatives or by themselves and despite being recognized as something abnormal, many of them come when the tremor intervenes with the activities of daily life. At this point, the management of the disease would begin, making clear the importance of education for the population to attend abnormal situations on time and not in late stages, significantly improving the quality of life or the prognosis of the disease Parkinson's, as is the case that occurred in our institution; A 64-year-old female patient who presents with tremor in the fifth finger of the right hand, she mentions that it is more intense when there are apparently stress situations, hyposmia and sleep disturbances, going to different health centers where they were controlled the discomfort with essential medications, many of these not requiring a prescription, temporarily decreasing in intensity; This being the beginning of multi-causality for proper management from considering the first contact doctor as a resource manager with the use of diagnostic skills to recognize characteristic signs in early stages of the disease and the ability to maintain continuity with the patients and their families as a model of family system. Studies were determined that non-motor manifestations could appear months or years before they manifest as motor symptoms to give comprehensive management to patients from their first contact with the health centers closest to them. The diagnostic presumption and its referral to the neurology and timely treatment service, until evaluating the functionality and efficacy of health policies, avoiding the delay in pharmacological treatment and access to specific neuroimaging studies at any stage of the disease. Objective: The objective of this report is to present a clinical case of a patient diagnosed with Parkinson's disease, from its management in the first contact medical services to have comprehensive management by a neurologist, thus in this way the period of latency to start treatment. Methods: We present a clinical case of a 64-year-old patient who came to consultation due to a tremor in the fifth finger of the right hand.A review of her medical history is performed, and management by different specialties is identified, for mood disorders, insomnia, essential tremor in addition to allergic rhinitis, already with drug treatment with slight or no improvement. The patient underwent a neurological examination and imaging and laboratory studies. She was referred to the neurology service as soon as possible. Result: After the interrogation and physical examination, the patient was referred to the Neurology service to confirm the presumption of diagnosis as a movement disorder under study. This process is often called the "latency period" of the diagnosis. The present work is shown as a decisive factor in giving a verdict on this problem. It is known that this level of resolution takes into account the pillars of first contact medicine as health resource managers. In this way, pharmacological treatment was started with a decrease in tremor as a motor symptom and an increase in quality and amount of sleep, increased mood, and affect as non-motor symptoms. Conclusion: The patient is under established medical and pharmacological control, and the long diagnostic latency period could be evidenced, as it usually happens in many movement disorders or their early stages, in this case, Parkinson's disease. Likewise, the family doctor is an instrument that allows the resolution of more than 90% of health problems in general, and the proper management of the remaining percentage is multifactorial, as well as medical skill and experience, the capacity of the patient or the family members. in recognizing early-stage motor disorders and health systems that often make a referral to other medical specialties difficult.


2018 ◽  
Vol 10 ◽  
pp. 117957351880358 ◽  
Author(s):  
Ashish Kumar Gupta ◽  
Komal Rani ◽  
Surabhi Swarnkar ◽  
Gaurav Khunger Kumar ◽  
Mohd Imran Khan ◽  
...  

Aim of the Study: Parkinson’s disease and schizophrenia are disease end points of dopaminergic deficit and hyperactivity, respectively, in the mid brain. Accordingly, current medications aim to restore normal dopamine levels, overshooting of which results in adverse effects of psychosis and extra-pyramidal symptoms, respectively. There are currently no available laboratory tests to guide treatment decisions or help predict adverse side effects of the drugs. The aim was to therefore explore the possibility of using apolipoprotein E as a biomarker to monitor pharmacological intervention in dopamine dictated states of Parkinson’s disease and schizophrenia for optimum therapy. Methods: Naïve and treated, Parkinson’s disease and schizophrenic patients were recruited from neurology and psychiatry clinics. Serum of healthy volunteers was collected as controls. Serum concentrations of apolipoprotein E was estimated by enzyme-linked immunosorbent assay (ELISA). Pathway analysis was carried out to delineate the interactions of apolipoprotein E in Parkinson’s disease and schizophrenia. Results: Apolipoprotein E levels are higher in Parkinson’s disease patients as compared with schizophrenic samples ( P < .05). Also, post-treatment apolipoprotein E levels in both disease states were at par with levels seen in healthy controls. The interactions of apolipoprotein E validate the results and place the differential expression of the protein in Parkinson’s disease and schizophrenia in the right perspective. Conclusion: Apolipoprotein E concentration across the dopaminergic spectrum suggests that it can be pursued not only as a potential biomarker in schizophrenia and Parkinson’s disease, but can also be an effective tool for clinicians to determine efficacy of drug-based therapy.


2021 ◽  
Vol 13 ◽  
Author(s):  
Song’an Shang ◽  
Hongying Zhang ◽  
Yuan Feng ◽  
Jingtao Wu ◽  
Weiqiang Dou ◽  
...  

Background: Cognitive deficits are prominent non-motor symptoms in Parkinson’s disease (PD) and have been shown to involve the neurovascular unit (NVU). However, there is a lack of sufficient neuroimaging research on the associated modulating mechanisms. The objective of this study was to identify the contribution of neurovascular decoupling to the pathogenesis of cognitive decline in PD.Methods: Regional homogeneity (ReHo), a measure of neuronal activity, and cerebral blood flow (CBF), a measure of vascular responses, were obtained from patients with PD with mild cognitive impairment (MCI) and normal cognition (NC) as well as matched healthy controls (HCs). Imaging metrics of neurovascular coupling (global and regional CBF-ReHo correlation coefficients and CBF-ReHo ratios) were compared among the groups.Results: Neurovascular coupling was impaired in patients with PD-MCI with a decreased global CBF-ReHo correlation coefficient relative to HC subjects (P &lt; 0.05). Regional dysregulation was specific to the PD-MCI group and localized to the right middle frontal gyrus, right middle cingulate cortex, right middle occipital gyrus, right inferior parietal gyrus, right supramarginal gyrus, and right angular gyrus (P &lt; 0.05). Compared with HC subjects, patients with PD-MCI showed higher CBF-ReHo ratios in the bilateral lingual gyri (LG), bilateral putamen, and left postcentral gyrus and lower CBF-ReHo ratios in the right superior temporal gyrus, bilateral middle temporal gyri, bilateral parahippocampal gyri, and right inferior frontal gyrus. Relative to the HC and PD-NC groups, the PD-MCI group showed an increased CBF-ReHo ratio in the left LG, which was correlated with poor visual–spatial performance (r = −0.36 and P = 0.014).Conclusion: The involvement of neurovascular decoupling in cognitive impairment in PD is regionally specific and most prominent in the visual–spatial cortices, which could potentially provide a complementary understanding of the pathophysiological mechanisms underlying cognitive deficits in PD.


2018 ◽  
Vol 55 ◽  
pp. 128-133 ◽  
Author(s):  
Angus D. Macleod ◽  
Rachel Henery ◽  
Paul C. Nwajiugo ◽  
Nicholas W. Scott ◽  
Robert Caslake ◽  
...  

2002 ◽  
Vol 11 (3) ◽  
pp. 185-193 ◽  
Author(s):  
K. A. Baker ◽  
M. B. Purdy ◽  
D. Sadi ◽  
K. Mukhida ◽  
I. Mendez

Optimal placement of intrastriatal dopaminergic grafts is likely crucial to optimize clinical recovery in Parkinson's disease (PD). The target sites of dopaminergic grafts vary among clinical trials and may partially explain the variable results in clinical efficacy reported thus far. In this study we hypothesized that a subsequent dopaminergic graft may promote functional recovery following a suboptimal initial graft. To test this hypothesis, rats with unilateral 6-hydroxydopamine lesions of the right nigrostriatal pathway were randomly divided into three groups. The first group received 900,000 fetal nigral cells in the medial striatum only (n = 6). The second group received 900,000 cells in both the medial and lateral striatum simultaneously (1.8 million total; n = 8). The final group received a second graft of 900,000 cells in the lateral striatum 6 weeks following initial transplantation of a medial graft (n = 6). Amphetamine-induced circling behavior was significantly reduced in both simultaneous and sequential graft groups at 9 and 12 weeks following transplantation of the initial graft. However, no recovery was noted in the single medial graft group at those time points. Furthermore, increased survival of dopaminergic cells was observed in the lateral graft of sequentially grafted animals compared with the medial graft. We conclude that a well-positioned subsequent graft can restore function in animals with a suboptimal initial graft and that the initial graft may improve survival of the second graft. These results are further discussed in relation to their important clinical implication for neural transplantation in PD.


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