scholarly journals Προσδιορισμός των επιπέδων της α-συνουκλεΐνης στο εγκεφαλονωτιαίο υγρό και το πλάσμα ασθενών με νόσο Parkinson, άνοια της νόσου Parkinson και άνοια με σωμάτια Lewy

2019 ◽  
Author(s):  
Αναστασία Μπουγέα

Θεωρητικό υπόβαθρο: Η νόσος του Πάρκινσον(PD), η άνοια στη νόσο του Πάρκινσον (PDD) και η άνοια με τα σώματα Lewy (DLB) αποτελούν κλινικά σύνδρομα γνωστά ως διαταραχές των σωματίων Lewy (LBD) επειδή έχουντα σωμάτια Lewyως κοινό παθολο-ανατομικό χαρακτηριστικό. Δεδομένου ότι η διάγνωσή τους παραμένει κυρίως κλινική, υπάρχει μεγάλο ενδιαφέρον για τη χρήση ενός ή περισσοτέρων βιοδεικτών για την έγκαιρη και έγκυρη διάγνωση και τη διαφορική διάγνωση μεταξύ αυτών των διαφορετικών μορφών παρκινσονισμού. Η α-συνουκλεΐνη (α-Syn) έχει κερδίσει την προσοχή ως εν δυνάμει βιοδείκτηςγια τις συνουκλεϊνοπάθειες. Ωστόσο,ο προσδιορισμός της ολικής α-Syn στο εγκεφαλονωτιαίο υγρό (ΕΝΥ) με τη μέθοδο ELISA και άλλες παρόμοιες τεχνικές απέδωσε αντικρουόμενα αποτελέσματα. Αντίστοιχες μελέτες της α-Syn στο πλάσμα/ορό έχουν επίσης δώσει αβέβαια αποτελέσματα. Τέτοιες αποκλίσεις έχουν συχνά αποδοθεί σε προ-αναλυτικούς και αναλυτικούς συγχυτικούς παράγοντες (ημερήσια διακύμανση, κεφαλοουραία διαβάθμιση της συγκλεντρωσης εντός του κεντρικού νευρικού συστήματος, το φύλο, την ηλικία και, κυρίως, η επιμόλυνση του ΕΝΥ από αίμα), στις διαφορετικές μεθόδους ELISA και στη μέτρηση διαφορετικών τύπων της α-Syn στο ΕΝΥ και το πλάσμα. Σκοπός: Έτσι, λαμβάνοντας υπόψη τις αδυναμίες των προηγούμενων ερευνών, η παρούσα διατριβή στοχεύει να ελέγξει για πιθανή διαφορά των επιπέδων της α-Syn στο ΕΝΥ, τον ορό και το πλάσμα ανάμεσα σε ασθενείς με νόσο PD, PDD, DLB και υγιείς μάρτυρες και τη διαγνωστική της αξία χρησιμοποιώντας βέλτιστες δυνατές μεθόδους και αυστηρή τήρηση των προαναλυτικών και αναλυτικών κατευθυντήριων οδηγιών.Μεθοδολογία: Στη μελέτη συμμετείχαν 77 ασθενείς (30 με PD, 18 με PDD και 29 με DLB) οι οποίοι νοσηλευτηκαν στην Α΄ Νευρολογική κλινική του Αιγινητείου Νοσοκομείου της Ιατρικής Σχολής του Πανεπιστημίου Αθηνών. Η διάγνωση ετέθη βάσει των πλέον πρόσφατων διαγνωστικών κλινικών κριτηρίων. Σε όλους τους ασθενείς ελήφθη πλήρες ιστορικό και διενεργήθηκε ενδελεχής αντικειμενική νευρολογική εξέταση. Επίσης υποβλήθησαν σε πλήρη κλινικοεργαστηριακό και απεικονιστικό έλεγχο, συμπεριλαμβανομένου τομοσπινθηρογραφήματος βασικών γαγγλίων με 123Ι-ioflupane (SPECT). Επίσης διενεργήθηκε νευροψυχολογικός έλεγχος με τις κάτωθι δοκιμασίες: Mini Mental State Examination (MMSE), CLOX 1-2, Frontal Assessment Battery (FAB), Clinical Dementia Rating (CDR), Neuropsychiatric Inventory (NPI),Questionnaire for Impulsive-Compulsive Disorder in Parkinson's Disease-Rating Scale (QUIP) και Instrumental Activities of Daily Living (IADL). Η κινητική αναπηρία των παρκινσονικών ασθενών αξιολογήθηκε με βάση την κλίμακα Unified Parkinson's Disease Rating Scale (UPDRS Ι-ΙV), η σταδιοποίησή τους με τις κλίμακες των Hoehn και Yahrκαι των Schwab και England. Η ομάδα ελέγχου αποτελείται από 30 υγιή άτομα χωρίς ιστορικό νευρολογικής ή ψυχιατρικής νόσου και φυσιολογική βαθμολογία στις ανωτέρω δοκιμασίες και κλίμακες. Όλοι οι συμμετέχοντες υποβλήθηκαν σε οσφυϊκή παρακέντηση μεταξύ 9-12 π.μ. μετά από ολονύκτια νηστεία. Δείγματα ΕΝΥ και πλάσματος/ ορού ελήφθησαν σε σωληνάρια από πολυπροπυλένιο, φυγοκεντρήθηκαν σε 2000xg για 10 λεπτά και αποθηκεύτηκαν στους -80 ° C μέχρι την ανάλυση. Δείγματα ΕΝΥ με περισσότερα από 50 ερυθρά αιμοσφαίρια απορρίφθηκαν. Αποτελέσματα: Η ηλικία κατά την έναρξη της νόσου ήταν μεγαλύτερη στους ασθενείς με DLB και οι βαθμολογίες MMSE ήταν υψηλότερες σε ασθενείς με PD. Μεγαλύτερες μέσες τιμές UPDRS-III καταγράφηκαν στους PDD και χαμηλότερες σε ασθενείς με PD. Μετά τη διόρθωση του Bonferroni διαπιστώθηκαν σημαντικά χαμηλότερες τιμές του Αβ42 σε ασθενείς με DLB σε σύγκριση με μάρτυρες (p = 0,002), ασθενείς με PD (p <0,001) και ασθενείς με PDD (p = 0,021). Επιπλέον, ηΤΡ-181 είχε σημαντικά χαμηλότερες τιμές σε ασθενείς με PD σε σύγκριση με ασθενείς με DLB (p = 0,028). Μεγαλύτερες τιμές α-Syn στο ΕΝΥ βρέθηκαν σε ασθενείς με DLB σε σύγκριση με τους μάρτυρες (p <0,001), ασθενείς με PD (p <0,001) και με PDD (p <0,001). Η ομάδα έλεγχου είχε σημαντικά χαμηλότερες τιμές α-Syn ορού σε σύγκριση με τους ασθενείς με PD (p <0,001), με PDD (p <0,001) και με DLB (p <0,001). Επιπλέον, οι ασθενείς με PDD είχαν σημαντικά υψηλότερες τιμές του πλάσματος α-Syn σε σύγκριση με τους μάρτυρες (p= 0,023). Ανεξαρτήτως ομάδας ασθενών, τα επίπεδα της α-Syn στο ΕΝΥ συσχετίζονταν σημαντικά με την Aβ42, ενώ τα επίπεδα της α-Syn στο πλάσμα συσχετίζονταν με την Τp-181. Αφαιρώντας τους 7 ασθενείς με DLB με προφιλ ΕΝΥ παθολογίας τύπου Alzheimer (Τt≥ 376, Aβ42≤580 and ΤP-181≥ 62.5 pg/ml) ανεύρεθηκαν σημαντικά υψηλότερες τιμές για την α-Syn ορού και πλάσματος αλλά οριακά για την πρωτεϊνη ΤP-181 στην ομάδα των LBDs συγκριτικά με την ομάδα ελέγχου. Η ανάλυση ROC έδειξε ότι οι α-Syn και Αβ42 στο ΕΝΥ είχαν την καλύτερη διακριτική ικανότητα μεταξύ PD και DLB. Επιπλέον, η διακριτική ικανότητα μεταξύ PDD και DLB ήταν παρόμοια για τις α-Syn και Αβ42 στο ΕΝΥ. Η α-Syn στον ορό έδειξε την καλύτερη διακριτική ικανότητα μεταξύ των PD και μαρτύρων ή μεταξύ PDD και μαρτύρων. Προέκυψαν τέλος οριακές συσχετίσεις μεταξύ βιοδεικτών της α-Syn και της Τp-181 και συγκεκριμένων νευροψυχολογικών/συμπεριφορικών κλιμάκων. Συμπεράσματα: Η α-Syn και η Αβ42 στο ΕΝΥ και τον ορο θα μπορούσαν να θεωρηθουν εν δυναμει βιοδεικτες για την διαφοροδιαγνωση των ασθενών στο φάσμα της LBD αφού έδειξαν την καλύτερη διακριτική ικανότητα μεταξύ των ομάδων PD- PDD και DLB. Εφ’ όσον επιβεβαιωθούν τα αποτελέσματα, η α-Syn του ορού, και, σε μικρότερο βαθμό, του πλάσματος, θα μπορούσαν να θεωρηθούν βιοδείκτες διάγνωσης των LBDs, καθώς εμφανίζουν υψηλότερες τιμές σε σχέση με άτομα ελέγχου.

Author(s):  
Mohammed Wasif Hussain ◽  
Richard Camicioli

AbstractSome nonmotor symptoms (NMS) of Parkinson’s disease (PD) have been shown to increase the risk of developing dementia. A total of 52 PD patients without dementia at baseline were examined for NMS over 36 months. Mini-Mental State Examination, Dementia Rating Scale–2, and caregiver-derived (Clinical Dementia Rating) scores were employed to rate patients as having either clear progression or not. Some 20 of 48 participants (41.7%) had clear cognitive decline. Univariate binary regression analysis was statistically significant for age (odds ratio [OR] (CI95%)=1.24, 1.07–1.45, p=0.006) and orthostatic hypotension (OH) (OR (CI95%)=4.91, 1.24–19.5, p=0.024). Multivariate analysis showed that only age (OR (CI95%)=1.19, 1.0–1.41, p=0.05) and OH (OR (CI95%)=5.57, 1.0–30.97, p=0.05) were correlated with an increased risk of cognitive decline. The presence of OH at baseline may be a significant predictor of progression to dementia in PD.


1997 ◽  
Vol 87 (1) ◽  
pp. 52-59 ◽  
Author(s):  
Oleg Kopyov ◽  
Deane Jacques ◽  
Christopher Duma ◽  
Galen Buckwalter ◽  
Alex Kopyov ◽  
...  

✓ The outcome of radiofrequency-guided posteroventral medial pallidotomy was investigated in 29 patients with recalcitrant Parkinson's disease. Extracellular recordings were obtained in the target region to differentiate the internal from the external globus pallidus, and distinct waveforms were recorded in each region. Stimulation of the target site further verified the lesion location. Of the 29 patients treated during the course of 1 year, none showed any adverse side effects (such as hemianopsia or hemiparesis) from the procedure. Significant and immediate improvement in motor involvement (dyskinesia, rigidity, dystonia, freezing, and tremor) was observed as measured by the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr scale. Patients experienced improvements in their condition as measured on a self-rating scale, and their ability to perform the activities of daily living was also significantly improved. Although the onset and duration of the effect of a single dose of levodopa did not change, the number of hours in an “off” state of dyskinesia per day was significantly decreased. These results provide further evidence, in a large group of patients, that posteroventral medial pallidotomy results in significant control of the motor symptoms of Parkinson's disease with a minimum of undesirable side effects.


2021 ◽  
Vol 11 ◽  
Author(s):  
Aleksandra A. Szwedo ◽  
Camilla Christina Pedersen ◽  
Anastasia Ushakova ◽  
Lars Forsgren ◽  
Ole-Bjørn Tysnes ◽  
...  

Objectives: To evaluate the impact of SNCA polymorphisms originally identified as risk factors for Parkinson's disease (PD) on the clinical presentation and progression of the disease in a large cohort of population-based patients with incident PD.Methods: Four hundred thirty-three patients and 417 controls from three longitudinal cohorts were included in the study. Disease progression was recorded annually for up to 9 years using the Unified Parkinson's Disease Rating Scale (UPDRS) or Mini-Mental State Examination. Genotypes for five variants within the SNCA locus (rs2870004, rs356182, rs5019538, rs356219, and rs763443) were determined. We studied the association between each variant and disease progression using linear mixed-effects regression models.Results: The clinical profile of the patients with PD at the point of diagnosis was highly uniform between genotype groups. The rs356219-GG genotype was associated with a higher UPDRS II score than A-allele carriers (β = 1.52; 95% confidence interval 0.10–2.95; p = 0.036), but no differences were observed in the rate of progression of the UPDRS II scores. rs356219-GG was also associated with a faster annual change in Mini-Mental State Examination score compared with A-carriers (β = 0.03; 95% confidence interval 0.00–0.06; p = 0.043).Conclusions: We show that the known PD-risk variant rs356219 has a minor effect on modifying disease progression, whereas no differences were associated with rs2870004, rs356182, rs5019538, and rs763443. These findings suggest that SNCA variants associated with PD risk may not be major driving factors to the clinical heterogeneity observed for PD.


2017 ◽  
Vol 32 (5) ◽  
pp. 789-793 ◽  
Author(s):  
Krisztina Horváth ◽  
Zsuzsanna Aschermann ◽  
Márton Kovács ◽  
Attila Makkos ◽  
Márk Harmat ◽  
...  

Neurology ◽  
2001 ◽  
Vol 57 (3) ◽  
pp. 481-488 ◽  
Author(s):  
R. C. Mohs ◽  
R. S. Doody ◽  
J.C. Morris ◽  
J. R. Ieni ◽  
S. L. Rogers ◽  
...  

Objective: To examine the effects of donepezil compared with placebo on the preservation of function in patients with AD over a 1-year period.Methods: This was a prospective, 54-week, double-blind, placebo-controlled, survival to endpoint study. Patients were required to have at entry: a diagnosis of probable AD (National Institute of Neurological and Communicative Disorders and Stroke criteria); Mini-Mental State Examination score of 12 to 20; Clinical Dementia Rating of 1 or 2; modified Hachinski ischemia score ≤4; and capability of performing 8 of 10 instrumental activities of daily living and 5 of 6 basic activities of daily living. Patients (n = 431) were randomized to placebo or donepezil (5 mg/day for 28 days, 10 mg/day thereafter). Outcome measures were the AD Functional Assessment and Change Scale, the Mini-Mental State Examination, and Clinical Dementia Rating scale. At each visit, investigators determined whether predefined criteria for clinically evident decline in functional status had been met. Patients who met the endpoint criteria were discontinued per protocol.Results: Donepezil extended the median time to clinically evident functional decline by 5 months versus placebo. The probability of patients treated with donepezil remaining in the study with no clinically evident functional loss was 51% at 48 weeks, compared with 35% for placebo. The Kaplan–Meier survival curves for the two treatment groups were different (p = 0.002, log-rank test).Conclusions: Patients with AD continue to show detectable disease progression over time, but treatment with donepezil for 1 year was associated with a 38% reduction in the risk of functional decline compared with placebo.


2007 ◽  
Vol 29 (4) ◽  
pp. 350-353 ◽  
Author(s):  
Jefferson C Folquitto ◽  
Sonia E Z Bustamante ◽  
Sérgio B Barros ◽  
Dionisio Azevedo ◽  
Marcos A Lopes ◽  
...  

OBJECTIVES: To investigate the applicability of the Bayer - Activities of Daily Living scale and its efficiency in differentiating individuals with mild to moderate dementia from normal elderly controls. METHOD: We selected 33 patients with diagnosis of mild to severe dementia, according to ICD-10 criteria, and 59 controls. All the subjects were evaluated with the Mini-Mental State Examination and the Clinical Dementia Rating Scale and the Bayer - Activities of Daily Living scale was applied to informants. RESULTS: The internal consistency of the Bayer - Activities of Daily Living was high (Cronbach's alpha = 0.981). Mean Mini-Mental State Examination and Bayer - Activities of Daily Living scores of demented patients and controls were significantly different (p < 0.001). Mean Mini-Mental State Examination and Bayer - Activities of Daily Living scores were significantly different between Clinical Dementia Rating Scale 0 (controls; n = 59) versus Clinical Dementia Rating Scale 1 (mild dementia; n = 15), Clinical Dementia Rating Scale 0 versus Clinical Dementia Rating Scale 2 (moderate dementia; n = 13), and for Clinical Dementia Rating Scale 1 versus Clinical Dementia Rating Scale 2 (p < 0.003). DISCUSSION: The Bayer - Activities of Daily Living scale and Mini-Mental State Examination differentiated elderly controls from patients with mild or moderate dementia, and patients with mild dementia from those with moderate dementia. CONCLUSIONS: The results suggest that the Bayer - Activities of Daily Living scale applied to an informant can help in the diagnosis and follow-up of Brazilian patients with mild to moderate dementia.


2017 ◽  
Vol 75 (8) ◽  
pp. 497-502 ◽  
Author(s):  
Raissa Carla Moreira ◽  
Marise Bueno Zonta ◽  
Ana Paula Serra de Araújo ◽  
Vera Lúcia Israel ◽  
Hélio A. G. Teive

ABSTRACT Objective To investigate which factors are associated with the quality of life decline in Parkinson’s disease patients from mild to moderate stages. Methods The Unified Parkinson’s Disease Rating Scale and Parkinson’s Disease Questionnaire-39 were used to evaluate clinical/functional data and the quality of life. Results The markers of clinical/functional worsening were drooling (p < 0.004), need for assistance with hygiene (p = 0.02), greater freezing frequency (p = 0.042), bradykinesia (p = 0.031), greater intensity of the resting tremor (p = 0.035) and “pill rolling” (p = 0.001). The decline in quality of life was related to stigma (p = 0.043), greater impairment in cognition (p = 0.002), mobility (p = 0.013) and for daily living activities (p = 0.05), and was considered more significant in men, married, older individuals, and those with a longer time of disease. Conclusions The quality of life worsening markers at the moderate stage were related to stigma, worsening of cognition, and to greater impairment in mobility and daily living activities.


1996 ◽  
Vol 5 (2) ◽  
pp. 327-337 ◽  
Author(s):  
Oleg V. Kopyov ◽  
Deane “Skip” Jacques ◽  
Abraham Lieberman ◽  
Christopher M. Duma ◽  
Robert L. Rogers

This study reports our findings from 22 patients (ages ranging from 42 to 73 yr; mean = 55.2) with recalcitrant idiopathic Parkinson's disease (PD) who received implants of fetal ventral mesencephalic tissue using an MRI-guided stereotactic procedure and who have been followed for at least 6 mo postoperatively, employing the guidelines established by the Core Assessment Program for Intracerebral Transplantations. Evaluations were videotaped and were performed both on and off levodopa medications. To date, we have seven patients with 24 mo, three with 18 mo, three with 12 mo, and nine with 6 mo of postsurgical assessments. Comparing surgical outcomes to levels prior to fetal transplants we found: 1) mean levodopa levels were reduced 46% at 6 mo, 12% at 12 mo, 20% at 18 mo, and 54% at 24 mo; 2) Unified Parkinson's Disease Rating Scale (UPDRS) scores with patients on levodopa were improved by an average of 38% (6 mo), 50.2% (12 mo), 69.3% (18 mo), and 73.9% (24 mo), while off medication scores showed reductions ranging from 24.7% at 6 mo to 55.1% at 24 mo. Other measures, including Hoehn-Yahr staging, Activities of Daily Living, and dyskinesia rating scales, were also significantly improved following fetal transplants. Timed motor tasks (finger dexterity, supination-pronation, foot tapping, and Stand-Walk-Sit) performance also demonstrated highly significant improvements. Patient's self-rating scores indicated that the patients typically perceived substantial improvements in their condition. However, substantial variability in the improvements following surgery still persists and range from nominal improvements in performance to significant changes that can be classified as altering the overall lifestyle of the patients. To date, 4 of the 22 subjects were considered by the physicians to be nonresponders; that is, there were no clinically relevant improvements in these patients' conditions.


2010 ◽  
Vol 68 (6) ◽  
pp. 855-861 ◽  
Author(s):  
Sheilla de Medeiros Correia ◽  
Lilian Schafirovits Morillo ◽  
Wilson Jacob Filho ◽  
Leticia Lessa Mansur

OBJECTIVE: To characterize the problems of feeding and swallowing in individuals with moderate and severe Alzheimer´s disease (AD) and to correlate these with functional aspects. METHOD: Fifty patients with AD and their caregivers participated in this study. The instruments used were: Clinical Dementia Rating (CDR), Mini-Mental State Examination, Index of Activities of Daily Living, Assessment of Feeding and Swallowing Difficulties in Dementia, Functional Outcome Questionnaire for Aphasia, and Swallowing Rating Scale. RESULTS: Problems with passivity, distraction and refusal to eat were encountered in the CDR2 group. Distraction, passivity and inappropriate feeding velocity were predominant in the CDR3 group. The problems were correlated with communication, swallowing severity of AD individuals and caregiver schooling. CONCLUSION: Given the inexorable functional alterations during the course of the disease, it is vital to observe these in patients with a compromised feeding and swallowing mechanism. The present study supplies the instruments to orient caregivers and professionals.


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