Top PDF Genetics of Parkinson’s Disease - A Clinical Perspective

Genetics of Parkinson’s Disease - A Clinical Perspective

Genetics of Parkinson’s Disease - A Clinical Perspective

Discovering genes following Medelian inheritance, such as autosomal dominant-synuclein and leucine-rich repeat kinase 2 gene, or autosomal recessive Parkin, P-TEN-induced puta- tive kinase 1 gene and Daisuke-Junko 1 gene, has provided great insights into the pathogen- esis of Parkinson’s disease (PD). Genes found to be associated with PD through investigat- ing genetic polymorphisms or via the whole genome association studies suggest that such genes could also contribute to an increased risk of PD in the general population. Some envi- ronmental factors have been found to be associated with genetic factors in at-risk patients, further implicating the role of gene-environment interactions in sporadic PD. There may be confusion for clinicians facing rapid progresses of genetic understanding in PD. After a brief review of PD genetics, we will discuss the insight of new genetic discoveries to clinicians, the implications of ethnic differences in PD genetics and the role of genetic testing for gen- eral clinicians managing PD patients. Journal of Movement Disorders 2012;5:33-41 Key Words: Parkinson’s disease, Genetics.
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Parkinson s disease and dopamine transporter neuroimaging: a critical review

Parkinson s disease and dopamine transporter neuroimaging: a critical review

However, variability in uptake values suggests that factors other than nigrostriatal degenera- tion may contribute towards disease severity. There is a correlation with bradykinesia but not with tremor, thus suggesting that the origin of tremors is beyond the DAT system. Another study comparing 18 PD patients with or without the Parkinsonism gene has now found that Parkinsonism-related disease may be associated with a higher degree of nigrostriatal impairment, independent of the clinical severity of the disease, and more symmetrical involvement than in non-Par- kinsonian early-onset disease. 102
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Blood Biomarkers Associated with Cognitive Decline in Early Stage and Drug-Naive Parkinson's Disease Patients.

Blood Biomarkers Associated with Cognitive Decline in Early Stage and Drug-Naive Parkinson's Disease Patients.

Early diagnosis of Parkinson’s disease (PD) continues to be a major challenge in the field. The lack of a robust biomarker to detect early stage PD patients has considerably slowed the progress toward the development of potential therapeutic agents. We have previously evaluated several RNA biomarkers in whole blood from participants enrolled in two inde- pendent clinical studies. In these studies, PD patients were medicated, thus, expression of these biomarkers in de novo patients remains unknown. To this end, we tested ten RNA bio- markers in blood samples from 99 untreated PD patients and 101 HC nested in the cross- sectional Parkinson’s Progression Markers Initiative by quantitative real-time PCR. One bio- marker out of ten, COPZ1 trended toward significance (nominal p = 0.009) when adjusting for age, sex, and educational level. Further, COPZ1, EFTUD2 and PTBP1 mRNAs corre- lated with clinical features in PD patients including the Hoehn and Yahr scale, Movement Disorder Society revision of Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Montreal Cognitive Assessment (MoCA) score. Levels of EFTUD2 and PTBP1 were signifi- cantly higher in cognitively normal PD patients (PD-CN) compared to cognitively impaired PD patients (PD-MCI). Interestingly, blood glucose levels were significantly higher in PD and PD-MCI patients ( 100 mg/dL, pre-diabetes) compared to HC. Collectively, we report the association of three RNA biomarkers, COPZ1, EFTUD2 and PTBP1 with clinical fea- tures including cognitive decline in early drug-naïve PD patients. Further, our results show that drug-naïve PD and PD-MCI patients have glucose levels characteristic of pre-diabetes patients, suggesting that impaired glucose metabolism is an early event in PD. Evaluation of these potential biomarkers in a larger longitudinal study is warranted.
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The Impact of Deep Brain Stimulation on the Quality of Life and Swallowing in Individuals with Parkinson ’s Disease

The Impact of Deep Brain Stimulation on the Quality of Life and Swallowing in Individuals with Parkinson ’s Disease

12 Fernandes GC, Socal MP, Schuh AFS, Rieder CRM. Clinical and Epidemiological Factors Associated with Mortality in Parkinson’s Disease in a Brazilian Cohort. Parkinsons Dis 2015;2015:959304 13 Lee JY, Kim DK, Seo KM, Kang SH. Usefulness of the simplified cough test in evaluating cough reflex sensitivity as a screening test for silent aspiration. Ann Rehabil Med 2014;38(04):476–484 14 Ciucci MR, Barkmeier-Kraemer JM, Sherman SJ. Subthalamic nucleus deep brain stimulation improves deglutition in Parkin- son’s disease. Mov Disord 2008;23(05):676–683

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Arq. NeuroPsiquiatr.  vol.74 número4

Arq. NeuroPsiquiatr. vol.74 número4

Increased of sexual arousal (ISA) has been described in different neurological diseases. The purpose of this study was present a case series of ISA in patients with movement disorders. Method: Fifteen patients with different forms of movement disorders (Parkinson’s disease, Huntington’s disease, Tourette´s syndrome, spinocerebellar ataxia type 3), were evaluated in the Movement Disorders Unit of the Federal University of Paraná. Results: Among Parkinson’s disease patients there were seven cases with different forms of ISA due to dopaminergic agonist use, levodopa abuse, and deep brain stimulation (DBS). In the group with hyperkinetic disorders, two patients with Huntington’s disease, two with Tourette’s syndrome, and four with spinocerebellar ataxia type 3 presented with ISA. Conclusions: ISA in this group of patients had different etiologies, predominantly related to dopaminergic treatment or DBS in Parkinson’s disease, part of the background clinical picture in Huntington’s disease and Tourette’s syndrome, and probably associated with cultural aspects in patients with spinocerebellar ataxia type 3. Keywords: hypersexual disorder; increased of sexual arousal; hypersexuality; movement disorders.
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Intra-Rater, Inter-Rater and Test-Retest Reliability of an Instrumented Timed Up and Go (iTUG) Test in Patients with Parkinson's Disease.

Intra-Rater, Inter-Rater and Test-Retest Reliability of an Instrumented Timed Up and Go (iTUG) Test in Patients with Parkinson's Disease.

Participant’s trunk movements were measured with a small and light (87×45×14 mm, 74 grams) inertial sensor measurement system (DynaPort Hybrid, McRoberts, The Hague, The Netherlands), which was inserted in an elastic belt and positioned on the lower back near the spine. The device measured acceleration and angular velocity in three directions at a rate of 100 samples/s. Several Sit-to-Stand (STS) parameters can be identified that provide a basis for a more precise, quantitative study of STS performance in clinical practice [16,17]. The patients started the TUG while sitting on a regular, stable chair, with a height of 43–46 cm, without armrests. Patients were instructed to sit with their back against the back of the chair, feet placed on taped markers on the floor directly in front of the chair, with a distance of 43 cm between the feet and arms resting in their lap. Patients were instructed to rise from the chair (without using their arms) after the rater gave the starting signal, comfortably walk the clearly marked distance of 3 meter, turn around a cone, walk back to the chair and sit down with their back against the chair. The 3 meter walking distance was measured from the front of the chair to the middle of the cone. Markers in the signals of the inertial sensors were set at the start and the end of every trial using a remote control (McRoberts B.V.) which uses Bluetooth to connect with the DynaPort sensor. The rater also used a stopwatch to measure the time needed to per- form the TUG, from the starting signal until the subject sat down on the chair again with the back against the back of the chair.
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Sixty hertz neurostimulation amplifies subthalamic neural synchrony in Parkinson's disease.

Sixty hertz neurostimulation amplifies subthalamic neural synchrony in Parkinson's disease.

Clinical evidence suggests that 60 Hz DBS may have a beneficial effect on axial motor behav- iors, such as freezing of gait and speech, but not on tremor [36–41]. In contrast, high frequency DBS appears to be therapeutic for tremor but not always for freezing of gait or speech. Howev- er, results have varied among studies and among individuals. The results of this investigation demonstrated heterogeneity among STNs regarding the effect of 60 Hz DBS on baseline neural synchrony, and it is possible that this may contribute to the heterogenic clinical effects of 60 Hz DBS in PD reported so far. We have shown previously that the resting state STN spectral profile is stationary but varies among subjects [7,28,32]. We propose that one explanation for whether high or low frequency DBS is or is not therapeutic for different motor behaviors may lie in the resonant frequency of the nested loops pertinent to the networks mediating such be- haviors. These may vary across the population, and may also be affected by amplitude- or frequency-modulation of interconnecting circuits. We demonstrate here that neurostimulation itself can be a powerful tool, whereby it is possible to “knock-in” and “knock-out” patient- specific bands of neural synchrony to determine their causal influences on human behaviors.
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Gene Expression Differences in Peripheral Blood of Parkinson ’s Disease Patients with Distinct Progression Profiles

Gene Expression Differences in Peripheral Blood of Parkinson ’s Disease Patients with Distinct Progression Profiles

To the best of our knowledge, this is the first study aimed at identifying molecular pathways distinguishing PD progression in peripheral blood. In total, we report novel, relevant genes that can be scrutinized in prospective studies, and that may prove valuable for distinguishing rapid versus slow PD progression phenotypes. Our findings suggest a possible mechanistic link between altered DNA synthesis/repair systems, intracellular transport, immune response, tran- scription regulation and the prediction of PD prognosis. Despite certain limitations, such as the need for fully validating the identified gene expression differences in well-characterized, independent cohorts, and that the classification of slow versus rapid progression may be a sim- plified view of the known heterogeneous rates of disease progression, we were able to identify a molecular signature that distinguishes both groups of patients. In future studies, one might per- haps attempt to use other disease progression classifiers. In our study, we used a classification based on previous reports showing that the absence of motor instability after 10 or more years of symptom onset is related to a slower progression phenotype, but it should be clarified that, to the best of our knowledge, there are no standardized clinical scales to unambiguously distin- guish rapid from slow progressors thus far. Finally, our findings should be confirmed in longi- tudinal studies, due to obvious limitations of a cross-sectional study. In such longitudinal studies, it is possible that peripheral predictors of disease progression might be unequivocally identified, which would be an invaluable aid for both clinicians and patients suffering from PD.
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Rev. LatinoAm. Enfermagem  vol.20 número2

Rev. LatinoAm. Enfermagem vol.20 número2

Parkinson’s disease can cause disability and decrease the quality of life in its sufferers. The aim of this study was to evaluate the quality of life of a group of people with Parkinson’s disease and whether a relationship exists between time of evolution and severity of the disease. Secondary analysis was carried out on transversal data collected from 40 individuals with Parkinson’s disease registered in the Parkinson’s Association of Maringá, in Maringá- PR-Brazil. Measures: three instruments were applied: a socio-demographic questionnaire, the Hoenh and Yahr Scale and the Parkinson’s Disease Questionnaire (PDQ-39). According to PDQ-39, men referred to a lower quality of life, although, statistically, there was no signiicant difference between the two genders. Differences were only observed in the dimensions of “activities of daily living” and “social support”, in which men presented higher impairment, and “emotions” and “bodily discomfort”, where women showed higher impairment. Furthermore, severity of disease tended to lead to a perception of lower quality of life regarding the dimensions of “activities of daily living” and “cognition”, which is relevant to improve clinical guidance and intervention.
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Arq. NeuroPsiquiatr.  vol.70 número6

Arq. NeuroPsiquiatr. vol.70 número6

Movement disorders (MD) encompass acute and chronic diseases characterized by involuntary movements and/or loss of control or ef- ficiency in voluntary movements. In this review, we covered situations in which the main manifestations are MDs that pose significant risks for acute morbidity and mortality. The authors examine literature data on the most relevant MD emergencies, including those related to Parkinson`s disease, acute drug reactions (acute dystonia, neuroleptic malignant syndrome, serotonergic syndrome and malignant hyper- thermia), acute exacerbation of chronic MD (status dystonicus), hemiballism and stiff-person syndrome, highlighting clinical presentation, demographics, diagnosis and management.
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Arq. NeuroPsiquiatr.  vol.73 número3

Arq. NeuroPsiquiatr. vol.73 número3

Objective: Sleep disorders in Parkinson’s disease are very common. Polysomnography (PSG) is considered the gold standard for diagnosis. The aim of the present study is to assess the prevalence of nocturnal sleep disorders diagnosed by polysomnography and to determine the associated clinical factors. Method: A total of 120 patients with Parkinson’s disease were included. All patients underwent a standardized overnight, single night polysomnography. Results: Ninety-four (78.3%) patients had an abnormal PSG. Half of the patients fulfilled criteria for sleep apnea-hypopnea syndrome (SAHS); rapid eye movement behavior disorder (RBD) was present in 37.5%. Characteristics associated with SAHS were age (p = 0.049) and body mass index (p = 0.016). Regarding RBD, age (p , 0.001), left motor onset (p = 0.047) and levodopa equivalent dose (p = 0.002) were the main predictors. Conclusion: SAHS and RBD were the most frequent sleep disorders. Higher levodopa equivalent dose and body mass index appear to be risk factors for RBD and SAHS, respectively.
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Imaging Striatal Microglial Activation in Patients with Parkinson's Disease.

Imaging Striatal Microglial Activation in Patients with Parkinson's Disease.

The rs6791 polymorphism can be associated with the susceptibility, progression or disease protection [25]. For instance, healthy individuals with Ala147/Ala147 (i.e., HABs) have been associated with significantly higher level of low-density lipoprotein (LDL) than those with Ala147/Thr147 (i.e., MABs) and with Thr147/Thr147 (i.e., LABs) [26], and LDL has been asso- ciated with the risk of PD [27]. While these reports are highly suggestive, the clinical signifi- cance of this polymorphism in PD is yet to be determined. Similarly, despite the well- documented increase in the TSPO expression as a result of brain insult in ex-vivo brain tissue, the functional significance of the upregulated TSPO is still unclear [6]. One possibility is that this upregulation may be related to glial proliferation, migration, and phagocytosis [28] or secretion of inflammatory cytokines. [ 11 C](R)PK11195 reduced the expression of proinflam- matory cytokines in cultured human microglia [29]. Furthermore, increased TSPO levels in microglia and astrocytes may possibly increase neurosteroid synthesis at injury sites to pro- mote neurotropic and neuroprotective activity [30]. While the observations regarding the potential role of the polymorphism on TSPO binding may be quite intriguing, they are specula- tive and warrant further investigations.
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Clinical Characterization of Parkinson s Disease Patients Followed at CHCB Comparison with a control group

Clinical Characterization of Parkinson s Disease Patients Followed at CHCB Comparison with a control group

Para todos os doentes de Parkinson (n=38), relativamente à clínica, foram registadas as seguintes variáveis: idade de início da doença, gravidade da doença (através da escala modificada de Hoehn & Yahr para estadiamento e dos anos de duração da doença), dose de L- DOPA de libertação imediata atualmente em utilização, sintomas inaugurais da doença e sintomas no dia da avaliação. Os processos clínicos foram avaliados para os doentes e controlos (n = 32). Os marcadores inflamatórios medidos foram a proteína-C-reativa, a velocidade de hemossedimentação e citoquinas séricas (interleucinas 1β, 8, 6, 10, 12p70 e Fator de Necrose Tumoral). O sistema imunológico foi avaliado através do leucograma e o ácido úrico foi o marcador oxidativo utilizado. O hemograma também foi incluído para uma melhor caracterização da população do estudo. As citoquinas no soro foram medidas através do kit BD™ CBA Human Inflammatory Cytokines, através de citometria de fluxo, no laboratório do Centro de Investigação em Ciências da Saúde (CICS), da Universidade da Beira Interior. Os restantes parâmetros analíticos foram obtidos através das análises de rotina prescritos pelo médico responsável pelo respetivo doente, no Hospital Pêro da Covilhã.
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Nullity of GSTT1/GSTM1 related to pesticides is associatedwith Parkinson's disease

Nullity of GSTT1/GSTM1 related to pesticides is associatedwith Parkinson's disease

GSTM1 and GSTT1 did not need enzymatic restric- tion, and were identiied by the presence or the absence of the genes (null genotype). Post-PCR product was separated by 1.5% agarose gel electrophoresis, under constant elec- tric current of 150 V during 45 minutes, separating 423 base pairs fragments (GSTT1), 310 base pairs (CYP control) and 230 base pairs (GSTM1). A standard DNA sample (100 base pairs  –  Invitrogen) was used as comparison to the electro- phoretic bands. After the electrophoresis, the gel was stained by GelRed ®

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Clinics  vol.72 número11

Clinics vol.72 número11

Although increasing insight into the course and patho- mechanisms of PD has been achieved, including risk factors that increase mortality rates, much of the disease remains a mystery (5,10-12,19,20). Importantly, previous studies sug- gest that PD is not a benign condition and is occasionally associated with sudden unexpected death in PD (SUDPAR) (21,22).

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Sao Paulo Med. J.  vol.131 número2

Sao Paulo Med. J. vol.131 número2

Presence of a single lineage with free trisomy of chromosome 18 was the main abnormal- ity, observed in 90% of the cases. he remainder consisted of patients with mosaicism. Major gastrointestinal abnormalities were observed in eight patients (16%): two cases of esophageal atresia (4%), three of tracheoesophageal istula (6%) (one associated with esophageal atresia), one of diaphragmatic hernia (2%) and three of omphalocele (6%). Among these eight patients, ive (62%) were female. heir ages at the time of the initial evaluation ranged from one to 70 days (median 7.5 days). Only two patients (25%) presented a clinical suspicion of Edwards syn- drome. Additional abnormalities, including minor and major anomalies, were observed in all cases. hese included dysmorphic features like a clenched ist with overlapping ingers and major malformations like congenital heart defects. None had a chromosomal constitution with mosaicism. hree patients underwent surgical correction of their defects (one with esophageal atresia, one with tracheoesophageal istula and one with omphalocele). In all cases, the diagno- sis of Edwards syndrome was made only ater surgery.
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Arq Bras Endocrinol Metab  vol.57 número3 en v57n3a01

Arq Bras Endocrinol Metab vol.57 número3 en v57n3a01

This Special Edition presents four consensuses that show the Brazilian experien- ce in patient management, implementation of diagnostic and therapeutic proposals for the management of patients with Congenital Hypothyroidism, Subclinical Hy- pothyroidism, and Hyperthyroidism, besides a consensus on the best way to use and interpret Thyroid Function Tests.

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Avaliação dos efeitos imunomoduladores de estatinas e glicocorticoides na terapêutica ...

Avaliação dos efeitos imunomoduladores de estatinas e glicocorticoides na terapêutica ...

Crohn's disease (CD) and Ulcerative colitis (UC) are the main conditions that comprise the Inflammatory Bowel Diseases (IBD). The conventional drug therapies for IBD aim to attenuate the uncontrolled inflammation in the intestinal mucosa, to treat the complications and to extend clinical remission. However, all available drugs have unpredictable or limited effects. Glucocorticoids (GCs) are commonly anti-inflammatory drugs, which are associated to refractoriness and/or dependence in over half of IBD patients. On the other hand, statins have pleiotropic properties and the concomitant use with GCs has shown good prospects in several autoimmune and inflammatory diseases, including IBD. Despite the putative clinical improvement after combined use of GCs and statins in IBD, there is a lack of data indicating their additive effects on the immune system. Therefore, the purpose of this study was to evaluate the immune modulatory effects of the concomitant use of statins and GCs in experimental colitis induced by dextran sulfate sodium (DSS). The results showed that long- term use of GCs (dexamethasone - DX), alone or associated to statins (atorvastatin - ATO), did not improve the clinical signs and increased the death rates of C57BL/6 mice exposed to DSS, while the opposite was observed after treatment with statins alone. Short-term use of ATO (3 doses), alone or associated to DX, improved the clinical signs and histological parameters in DSS-exposed mice, decreased the number of white blood cells (mainly monocytes), the number of mononuclear cells in the lamina propria (LP), the frequency of CD11b + cells in the LP, the frequency of CD11b + CD11c + and CD11b - CD11c + dendritic cells
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Clinical case of Hailey-Hailey disease

Clinical case of Hailey-Hailey disease

The study presents a relatively rare case of dermatosis. It is familial benign chronic vesicular fever (Hailey–Hailey disease) in a 58-years old female patient which is inherited as an autosomal dominant mode. The data about etiology, pathogenesis, clinical picture and differential diagnosis were summarized. The main ways of treatment of the disease are described.

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Biologic and genetics aspects of chagas disease at endemic areas

Biologic and genetics aspects of chagas disease at endemic areas

Idiopathic achalasia and megaesophaus patients, with or without esophageal carcinoma, described changes in expres- sion of proteins such as p53, p16, and MIB (mindbomb homolog) [63–68], chromosomal aneuploidies [59, 69], gene deletions in significant (TP53) [69] or marginal levels (TP63, FHIT, PIK3CA, EGFR, CDKN2A, and YES) [70], and gene copy number gain (PIK3CA, TP63, FGFR1, MYC, CDNK2A, and NCOA3) mainly associated with dilation grades III and IV [70]. A strong immunoreactivity of p53 protein was found in patients with idiopathic and megaesophaus, and two of four cases analyzed showed mutations in TP53 codons 238 and 146 of exons 7 and 5, respectively [63]. The authors suggested that changes in TP53 in megaesophagus epithelium might be a useful biomarker for identifying individuals with high risk of carcinoma development. In other studies, the frequency of p53 protein immunoreactivity increased significantly when compared to patients with normal esophageal mucosa and achalasia [65, 66]. Thus, these studies suggest that the cell cycle may be altered due to persistent inflammation of mucosa cells, which may arise during dysplasia-carcinoma sequence.
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