bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal functional connectivity of the amygdala is associated with depression in Parkinson's disease
Authors: Hu Xiao , Song Xiaopeng , Yuan Yonggui , Li Erfeng , Liu Jiajia , Liu Weiguo , Liu Yijun 
Published: December 2014

ABSTRACTDepressive symptoms are common in Parkinson's disease (PD), but the pathophysiology and neural basis underlying depression in PD is not well understood. Abnormal functional connectivity of the amygdala with various cortical and subcortical areas has been observed in major depressive disorder, indicating that dysfunction of the corticolimbic network may be involved in the pathogenesis of major depressive disorder. However, little is known about alterations of amygdala functional connectivity in depressed PD patients. In the present study, 20 depressed PD patients, 40 nondepressed PD patients, and 43 matched healthy controls underwent neuropsychological tests and resting‐state functional MRI scanning. Between‐group differences in amygdala functional connectivity network were examined using t tests. Compared to the nondepressed PD patients, depressed PD patients showed increased left amygdala functional connectivity with the bilateral mediodorsal thalamus, right amygdala functional connectivity with the left superior temporal gyrus, and left calcarine gyrus. Compared to the healthy controls, the depressed PD group also showed increased left amygdala functional connectivity with the bilateral mediodorsal thalamus, but decreased left amygdala functional connectivity with the left putamen, left inferior frontal gyrus, and the right cerebellum, as well as decreased right amygdala functional connectivity with the left inferior orbitofrontal gyrus, the left gyrus rectus, and the right putamen. The increased connectivity between limbic regions and decreased connectivity between the corticolimbic networks may reflect impaired high‐order cortical regulatory effects on the emotion‐related limbic areas, which may lead to mood dysregulation. Our study should advance the understanding of neural mechanisms underlying depression in PD. © 2014 International Parkinson and Movement Disorder Society
A population‐based study on combined markers for early Parkinson's disease
Authors: Tunc Sinem , Graf Julia , Tadic Vera , Brüggemann Norbert , Schmidt Alexander , Al‐Khaled Mohamed , Wolff Simone , Vollstedt Eva‐Juliane , Lorwin Anne , Hampf Jennie , Piskol Linda , Klein Christine , Hagenah Johann , Kasten Meike 
Published: December 2014

AbstractThe prerequisite for an earlier diagnosis of Parkinson's disease (PD) are markers that are both sensitive and specific for clinically definite PD and its prediagnosic phases. Promising candidates include enlarged hyperechogenicity of the substantia nigra (SN+) on transcranial sonography (TCS) and hyposmia. However, despite good sensitivity and specificity, both markers have yet failed to yield reliable predictions. We pursue the possibility of combined use in an ongoing population‐based cohort. Subjects were recruited from 10,000 inhabitants of Luebeck/Germany aged 50 to 79 years and additional PD patients from our outpatient clinic. After neurological examination, 715 subjects were grouped into clinically definite PD (n = 106), possible prediagnostic PD (ppPD; n = 73), and a control group subdivided into healthy individuals (n = 283) and controls with diseases other than PD (n = 253). Subjects underwent TCS and smell testing. Sensitivity and specificity of SN+ and hyposmia were good for PD; however, positive predictive values (PPV) of both SN+ (5.2%) and olfaction (2.5%) were low. At least one positive/both positive markers were present in 33%/1% of healthy controls, 33%/2% of diseased controls, 62%/7% of ppPD, and 94%/51% of PD. When combining SN+ and hyposmia, PPV increased to 17.6%, with a sensitivity of 51% and a specificity of 98%. Both SN+ and hyposmia offer good enrichment towards PD and ppPD, are stable against other diseases, and the combination of markers highly increases specificity. However, if the combination of SN+ and hyposmia were used as criterion for PD diagnosis, almost half of clinically definite PD and more than 90% of ppPD would have been missed. © 2014 International Parkinson and Movement Disorder Society
The significance of motor (A)symmetry in Parkinson's disease
Authors: Marinus Johan , van Hilten Jacobus J. 
Published: December 2014

AbstractThis study was undertaken to evaluate whether the predominant motor distribution pattern (ie, symmetric or asymmetric) observed in patients with Parkinson's disease (PD) contributes independently to disease severity and progression. We further examine whether this pattern is stable over time, and whether a potential change in pattern affects the course of the disease. We used data from the longitudinal PROPARK study (N > 400) to examine the association of the predominant motor distribution pattern with motor, cognitive, depressive, psychotic, and autonomic symptoms, and with excessive daytime sleepiness. We found that a symmetrical distribution of motor features was associated with poorer performance on nearly all domains, but that this was entirely explained by confounding, in particular by higher age and longer disease duration. We also found that greater asymmetry was associated with younger age, younger age at onset, and shorter disease duration. We further observed a clear tendency to develop a more symmetric distribution pattern as the disease advanced. Conversion to a symmetric pattern was associated with more severe disease, but this conversion did not contribute independently to the less favorable disease course. With increasing age and disease duration comes a clear tendency to develop a more symmetric distribution of motor features in PD. Although this change in distribution pattern is associated with more severe disease as compared with nonconvertors, this pattern change did not contribute independently to the less favorable course. We discuss these findings in light of the evidence from the literature. © 2014 International Parkinson and Movement Disorder Society
Progression of gait dysfunction in incident Parkinson's disease: Impact of medication and phenotype
Authors: Galna Brook , Lord Sue , Burn David J. , Rochester Lynn 
Published: December 2014

AbstractGait impairment in Parkinson's disease (PD) persists despite the use of dopaminergic therapy. Motor phenotype associated with greater postural instability and gait difficulty is related to a greater risk of motor decline and may be influenced by non‐dopaminergic pathology. This study documents the progression of gait impairment over 18 months in an incident cohort of PD with regard to phenotype and medication. Gait characteristics were measured in 121 PD and 184 controls, and 18 months later in 108 PD participants. Sixteen gait characteristics were examined with respect to five broad domains for PD and motor phenotype. Correlations between change in levodopa (l‐dopa) equivalent daily dose and gait were used to identify dopa‐responsive and nonresponsive characteristics. Pace and rhythm deteriorated over 18 months in people with PD, with other gait domains remaining stable. People with a postural instability and gait difficulty phenotype had more impaired gait at baseline compared with a tremor‐dominant phenotype, which was most evident in temporal characteristics. In contrast, pace and variability deteriorated over the subsequent 18 months in the tremor‐dominant phenotype only. Weak but statistically significant correlations were found between increased l‐dopa medication and less deterioration in pace and asymmetry. Significant gait impairment is evident in very early disease despite optimal medication. Change over 18 months is subtle and discrete, and is more pronounced in the tremor‐dominant phenotype. Some features of gait are refractory to dopaminergic therapy, implicating a non‐dopaminergic contribution. This may explain more temporal gait disturbance in the postural instability and gait difficulty phenotype. © 2014 International Parkinson and Movement Disorder Society
Is the Parkinson anxiety scale comparable across raters?
Authors: Forjaz Maria João , Ayala Alba , Martinez‐Martin Pablo , Dujardin Kathy , Pontone Gregory M. , Starkstein Sergio E. , Weintraub Daniel , Leentjens Albert F. G. 
Published: December 2014

AbstractThe Parkinson Anxiety Scale is a new scale developed to measure anxiety severity in Parkinson's disease specifically. It consists of three dimensions: persistent anxiety, episodic anxiety, and avoidance behavior. This study aimed to assess the measurement properties of the scale while controlling for the rater (self‐ vs. clinician‐rated) effect. The Parkinson Anxiety Scale was administered to a cross‐sectional multicenter international sample of 362 Parkinson's disease patients. Both patients and clinicians rated the patient's anxiety independently. A many‐facet Rasch model design was applied to estimate and remove the rater effect. The following measurement properties were assessed: fit to the Rasch model, unidimensionality, reliability, differential item functioning, item local independency, interrater reliability (self or clinician), and scale targeting. In addition, test–retest stability, construct validity, precision, and diagnostic properties of the Parkinson Anxiety Scale were also analyzed. A good fit to the Rasch model was obtained for Parkinson Anxiety Scale dimensions A and B, after the removal of one item and rescoring of the response scale for certain items, whereas dimension C showed marginal fit. Self versus clinician rating differences were of small magnitude, with patients reporting higher anxiety levels than clinicians. The linear measure for Parkinson Anxiety Scale dimensions A and B showed good convergent construct with other anxiety measures and good diagnostic properties. Parkinson Anxiety Scale modified dimensions A and B provide valid and reliable measures of anxiety in Parkinson's disease that are comparable across raters. Further studies are needed with dimension C. © 2014 International Parkinson and Movement Disorder Society
Stem cell reprogramming: Basic implications and future perspective for movement disorders
Authors: Brändl Björn , Schneider Susanne A. , Loring Jeanne F. , Hardy John , Gribbon Philip , Müller Franz‐Josef 
Published: December 2014

AbstractThe introduction of stem cell‐associated molecular factors into human patient‐derived cells allows for their reprogramming in the laboratory environment. As a result, human induced pluripotent stem cells (hiPSC) can now be reprogrammed epigenetically without disruption of their overall genomic integrity. For patients with neurodegenerative diseases characterized by progressive loss of functional neurons, the ability to reprogram any individual's cells and drive their differentiation toward susceptible neuronal subtypes holds great promise. Apart from applications in regenerative medicine and cell replacement–based therapy, hiPSCs are increasingly used in preclinical research for establishing disease models and screening for drug toxicities. The rapid developments in this field prompted us to review recent progress toward the applications of stem cell technologies for movement disorders. We introduce reprogramming strategies and explain the critical steps in the differentiation of hiPSCs to clinical relevant subtypes of cells in the context of movement disorders. We summarize and discuss recent discoveries in this field, which, based on the rapidly expanding basic science literature as well as upcoming trends in personalized medicine, will strongly influence the future therapeutic options available to practitioners working with patients suffering from such disorders. © 2014 International Parkinson and Movement Disorder Society
Selective changes of ocular vestibular myogenic potentials in Parkinson's disease
Authors: Pötter‐Nerger Monika , Govender Sendhil , Deuschl Günther , Volkmann Jens , Colebatch J.G. 
Published: December 2014

ABSTRACTBackgroundVestibular evoked myogenic potentials represent electrophysiological tools to measure vestibular reflex actions at different levels of the brainstem in Parkinson's disease.ObjectiveTo investigate cervical and ocular vestibular myogenic potentials in Parkinsonian patients with mild disability.MethodsIn 13 Parkinsonian patients and 13 age‐matched healthy controls, cervical and ocular vestibular myogenic potentials were recorded after unilateral air‐conducted tone bursts and bone‐conducted stimuli delivered at the forehead or mastoids.ResultsIn contrast to relatively preserved cervical vestibular evoked myogenic potentials, ocular vestibular evoked myogenic potentials were significantly delayed and of reduced amplitude, particularly after impulsive stimulation in Parkinsonian patients. Levodopa had no significant effect on either type of response.ConclusionIn mild to moderate Parkinson's disease, altered ocular vestibular myogenic potentials may indicate early functional involvement of the upper brainstem, in contrast to preserved lower brainstem function as reflected by normal cervical vestibular myogenic potentials. © 2014 International Parkinson and Movement Disorder Society
A de novoADCY5 mutation causes early‐onset autosomal dominant chorea and dystonia
Authors: Carapito Raphael , Paul Nicodème , Untrau Meiggie , Le Gentil Marion , Ott Louise , Alsaleh Ghada , Jochem Pierre , Radosavljevic Mirjana , Le Caignec Cédric , David Albert , Damier Philippe , Isidor Bertrand , Bahram Seiamak 
Published: December 2014

ABSTRACTImportanceApart from Huntington's disease, little is known of the genetics of autosomal dominant chorea associated with dystonia. Here we identify adenylate cyclase 5 (ADCY5) as a likely new causal gene for early‐onset chorea and dystonia.ObservationsWhole exome sequencing in a three‐generation family affected with autosomal dominant chorea associated with dystonia identified a single de novo mutation—c.2088+1G>A in a 5' donor splice‐site of ADCY5—segregating with the disease. This mutation seeming leads to RNA instability and therefore ADCY5 haploinsufficiency.Conclusions and RelevanceOur finding confirms the genetic/clinical heterogeneity of the disorder; corroborated by previous identification of ADCY5 mutations in one family with dyskinesia‐facial myokymia and in two unrelated sporadic cases of paxoysmal choreic/dystonia‐facial myokymia; ADCY5's high expression in the striatum and movement disorders in ADCY5‐deficient mice. Hence ADCY5 genetic analyses may be relevant in the diagnostic workup of unexplained early‐onset hyperkinetic movement disorders. © 2014 International Parkinson and Movement Disorder Society
Vitamin D from different sources is inversely associated with Parkinson disease
Authors: Wang Liyong , Evatt Marian L. , Maldonado Lizmarie G. , Perry William R. , Ritchie James C. , Beecham Gary W. , Martin Eden R. , Haines Jonathan L. , Pericak‐Vance Margaret A. , Vance Jeffery M. , Scott William K. 
Published: December 2014

AbstractAn inverse association between Parkinson disease (PD) and total vitamin D levels has been reported, but whether vitamin D from different sources, that is, 25(OH)D2 (from diet and supplements) and 25(OH)D3 (mainly from sunlight exposure), all contribute to the association is unknown. Plasma total 25(OH)D, 25(OH)D2, and 25(OH)D3 levels were measured by liquid chromatography–tandem mass spectrometry in PD patients (n = 478) and controls (n = 431). Total 25(OH)D was categorized by clinical insufficiency or deficiency; 25(OH)D2 and 25(OH)D3 were analyzed in quartiles. Vitamin D deficiency (total 25[OH]D < 20 ng/mL) and vitamin D insufficiency (total 25[OH]D < 30 ng/mL) are associated with PD risk (odds ratio [OR] = 2.6 [deficiency] and 2.1 [insufficiency]; P < 0.0001), adjusting for age, sex, and sampling season. Both 25(OH)D2 and 25(OH)D3 levels are inversely associated with PD (Ptrend < 0.0001). The association between 25(OH)D2 and PD risk is largely confined to individuals with low 25(OH)D3 levels (Ptrend = 0.0008 and 0.12 in individuals with 25[OH]D3 < 20 ng/mL and 25[OH]D3 ≥ 20 ng/mL, respectively). Our data confirm the association between vitamin D deficiency and PD, and for the first time demonstrate an inverse association of 25(OH)D2 with PD. Given that 25(OH)D2 concentration is independent of sunlight exposure, this new finding suggests that the inverse association between vitamin D levels and PD is not simply attributable to lack of sunlight exposure in PD patients with impaired mobility. The current study, however, cannot exclude the possibility that gastrointestinal dysfunction, a non‐motor PD symptom, contributes to the lower vitamin D2 levels in PD patients. © 2014 International Parkinson and Movement Disorder Society
Olfactory dysfunction in Parkinson's disease: Positive effect of cigarette smoking
Authors: Sharer James D. , Leon‐Sarmiento Fidias E. , Morley James F. , Weintraub Daniel , Doty Richard L. 
Published: December 2014

ABSTRACTBackgroundThere is compelling evidence from over 60 epidemiological studies that smoking significantly reduces the risk of Parkinson's disease (PD). In general, those who currently smoke cigarettes, as well as those with a past history of such smoking, have a reduced risk of PD compared to those who have never smoked. Recently it has been suggested that a cardinal nonmotor sensory symptom of PD, olfactory dysfunction, may be less severe in PD patients who smoke than in PD patients who do not, in contrast to the negative effect of smoking on olfaction described in the general population.MethodsWe evaluated University of Pennsylvania Smell Identification Test (UPSIT) scores from 323 PD patients and 323 controls closely matched individually on age, sex, and smoking history (never, past, or current).ResultsPatients exhibited much lower UPSIT scores than did the controls (P < 0.0001). The relative decline in dysfunction of the current PD smokers was less than that of the never‐ and past‐PD smokers (respective Ps = 0.0005 and 0.0019). Female PD patients outperformed their male counterparts by a larger margin than did the female controls (3.66 vs. 1.07 UPSIT points; respective Ps < 0.0001 and 0.06). Age‐related declines in UPSIT scores were generally present (P < 0.0001). No association between the olfactory measure and smoking dose, as indexed by pack‐years, was evident.ConclusionsPD patients who currently smoke do not exhibit the smoking‐related decline in olfaction observed in non‐PD control subjects who currently smoke. The physiological basis of this phenomenon is yet to be defined. © 2014 International Parkinson and Movement Disorder Society
Ultrasound‐based motion analysis demonstrates bilateral arm hypokinesia during gait in heterozygous PINK1 mutation carriers
Authors: Nürnberger Lucas , Klein Christine , Baudrexel Simon , Roggendorf Julia , Hildner Marcel , Chen Shu , Kang Jun‐Suk , Hilker Rüdiger , Hagenah Johann 
Published: December 2014

AbstractCarriers of a single heterozygous PINK1 (PTEN‐induced putative kinase 1) gene mutation provide an ideal opportunity to study the development of parkinsonian motor signs from the very beginning. Measuring tools that reliably represent mild motor symptoms could also facilitate the assessment of future neuroprotective therapies and early diagnosis of Parkinson's disease (PD). We investigated nine family members carrying a heterozygous PINK1 mutation in comparison with 25 age‐matched healthy controls. Arm kinematics were quantified during treadmill walking at four different speeds using ultrasound‐based motion analysis. Heterozygous PINK1 mutation carriers showed a bilateral reduction of arm swing amplitudes (P = 0.003) and arm anteversion (P = 0.001), which was more pronounced on the predominantly affected body side but also was present, albeit to a lesser degree, contralaterally (amplitude P = 0.01, anteversion P = 0.002, repeated measures analysis of covariance [rmANCOVA]). Single post‐hoc comparisons revealed similar results for all speeds on both body sides (P < 0.05) except for 2.0 km/h on the less affected side. A single heterozygous mutation in the PINK1 gene is associated with a bilateral dopaminergic dysfunction in this family. Ultrasound‐based three‐dimensional motion analysis of arm swing during gait is a suitable tool to quantify even subtle hypokinesia in mildly affected PINK1 mutation carriers, which tends to be easily overlooked on the less affected body side during clinical examination. Therefore, this technique is a promising application in early stage PD and in at‐risk populations for the disease. © 2014 International Parkinson and Movement Disorder Society
H‐ABC syndrome and DYT4: Variable expressivity or pleiotropy of TUBB4 mutations?
Authors: Erro Roberto , Hersheson Joshua , Ganos Christos , Mencacci Niccoló E. , Stamelou Maria , Batla Amit , Thust Stefanie Catherine , Bras Jose M. , Guerreiro Rita J. , Hardy John , Quinn Niall P. , Houlden Henry , Bhatia Kailash P. 
Published: December 2014

AbstractRecently, mutations in the TUBB4A gene have been found to underlie hypomyelination with atrophy of the basal ganglia and cerebellum (H‐ABC) syndrome, a rare neurodegenerative disorder of infancy and childhood. TUBB4A mutations also have been described as causative of DYT4 (“hereditary whispering dysphonia”). However, in DYT4, brain imaging has been reported to be normal and, therefore, H‐ABC syndrome and DYT4 have been construed to be different disorders, despite some phenotypic overlap. Hence, the question of whether these disorders reflect variable expressivity or pleiotropy of TUBB4A mutations has been raised. We report four unrelated patients with imaging findings either partially or totally consistent with H‐ABC syndrome, who were found to have TUBB4A mutations. All four subjects had a relatively homogenous phenotype characterized by severe generalized dystonia with superimposed pyramidal and cerebellar signs, and also bulbar involvement leading to complete aphonia and swallowing difficulties, even though one of the cases had an intermediate phenotype between H‐ABC syndrome and DYT4. Genetic analysis of the TUBB4A gene showed one previously described and two novel mutations (c.941C>T; p.Ala314Val and c.900G>T; p.Met300Ile) in the exon 4 of the gene. While expanding the genetic spectrum of H‐ABC syndrome, we confirm its radiological heterogeneity and demonstrate that phenotypic overlap with DYT4. Moreover, reappraisal of previously reported cases would also argue against pleiotropy of TUBB4A mutations. We therefore suggest that H‐ABC and DYT4 belong to a continuous phenotypic spectrum associated with TUBB4A mutations. © 2014 International Parkinson and Movement Disorder Society
C‐terminal juxtamembrane region of full‐length M2 protein forms a membrane surface associated amphipathic helix
Authors: Huang Shenstone , Green Bryan , Thompson Megan , Chen Richard , Thomaston Jessica , DeGrado William F. , Howard Kathleen P. 
Published: December 2014

AbstractThe influenza A M2 protein is a 97‐residue integral membrane protein involved in viral budding and proton conductance. Although crystal and NMR structures exist of truncated constructs of the protein, there is disagreement between models and only limited structural data are available for the full‐length protein. Here, the structure of the C‐terminal juxtamembrane region (sites 50–60) is investigated in the full‐length M2 protein using site‐directed spin‐labeling electron paramagnetic resonance (EPR) spectroscopy in lipid bilayers. Sites 50–60 were chosen for study because this region has been shown to be critical to the role the M2 protein plays in viral budding. Continuous wave EPR spectra and power saturation data in the presence of paramagnetic membrane soluble oxygen are consistent with a membrane surface associated amphipathic helix. Comparison between data from the C‐terminal juxtamembrane region in full‐length M2 protein with data from a truncated M2 construct demonstrates that the line shapes and oxygen accessibilities are remarkably similar between the full‐length and truncated form of the protein.