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Find video protocols related to scientific articles indexed in Pubmed.
Cognitive impairment and resting-state network connectivity in Parkinson's disease.
Hum Brain Mapp
PUBLISHED: 08-28-2014
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The purpose of this work was to evaluate changes in the connectivity patterns of a set of cognitively relevant, dynamically interrelated brain networks in association with cognitive deficits in Parkinson's disease (PD) using resting-state functional MRI. Sixty-five nondemented PD patients and 36 matched healthy controls were included. Thirty-four percent of PD patients were classified as having mild cognitive impairment (MCI) based on performance in attention/executive, visuospatial/visuoperceptual (VS/VP) and memory functions. A data-driven approach using independent component analysis (ICA) was used to identify the default-mode network (DMN), the dorsal attention network (DAN) and the bilateral frontoparietal networks (FPN), which were compared between groups using a dual-regression approach controlling for gray matter atrophy. Additional seed-based analyses using a priori defined regions of interest were used to characterize local changes in intranetwork and internetwork connectivity. Structural group comparisons through voxel-based morphometry and cortical thickness were additionally performed to assess associated gray matter atrophy. ICA results revealed reduced connectivity between the DAN and right frontoinsular regions in MCI patients, associated with worse performance in attention/executive functions. The DMN displayed increased connectivity with medial and lateral occipito-parietal regions in MCI patients, associated with worse VS/VP performance, and with occipital reductions in cortical thickness. In line with data-driven results, seed-based analyses mainly revealed reduced within-DAN, within-DMN and DAN-FPN connectivity, as well as loss of normal DAN-DMN anticorrelation in MCI patients. Our findings demonstrate differential connectivity changes affecting the networks evaluated, which we hypothesize to be related to the pathophysiological bases of different types of cognitive impairment in PD. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
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An exome study of Parkinson's disease in Sardinia, a Mediterranean genetic isolate.
Neurogenetics
PUBLISHED: 07-21-2014
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Parkinson's disease (PD) is a common neurodegenerative disorder of complex aetiology. Rare, highly penetrant PD-causing mutations and common risk factors of small effect size have been identified in several genes/loci. However, these mutations and risk factors only explain a fraction of the disease burden, suggesting that additional, substantial genetic determinants remain to be found. Genetically isolated populations offer advantages for dissecting the genetic architecture of complex disorders, such as PD. We performed exome sequencing in 100 unrelated PD patients from Sardinia, a genetic isolate. SNPs absent from dbSNP129 and 1000 Genomes, shared by at least five patients, and of functional effects were genotyped in an independent Sardinian case-control sample (n?=?500). Variants associated with PD with nominal p value <0.05 and those with odds ratio (OR) ?3 were validated by Sanger sequencing and typed in a replication sample of 2965 patients and 2678 controls from Italy, Spain, and Portugal. We identified novel moderately rare variants in several genes, including SCAPER, HYDIN, UBE2H, EZR, MMRN2 and OGFOD1 that were specifically present in PD patients or enriched among them, nominating these as novel candidate risk genes for PD, although no variants achieved genome-wide significance after Bonferroni correction. Our results suggest that the genetic bases of PD are highly heterogeneous, with implications for the design of future large-scale exome or whole-genome analyses of this disease.
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Correlates of cerebrospinal fluid levels of oligomeric- and total-?-synuclein in premotor, motor and dementia stages of Parkinson's disease.
J. Neurol.
PUBLISHED: 07-04-2014
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High-oligomeric and low-total-?-synuclein cerebrospinal fluid (CSF) levels have been found in Parkinson's disease (PD), but with inconsistent or limited data, particularly on their clinical and structural correlates in earliest (premotor) or latest (dementia) PD stages. We determined CSF oligomeric- and total-?-synuclein in 77 subjects: 23 with idiopathic REM-sleep behaviour disorder (iRBD, a condition likely to include a remarkable proportion of subjects in the premotor stage of PD) and 41 with PD [21 non-demented (PDND) + 20 demented (PDD)], intended to reflect the premotor-motor-dementia PD continuum, along with 13 healthy controls. The study protocol also included the Unified PD Rating Scale motor-section (UPDRS-III), mini mental state examination (MMSE), neuropsychological cognitive testing, 3T brain MRI for cortical-thickness analyses, CSF ? and CSF A?. CSF oligomeric-?-synuclein was higher in PDND than iRBD and in PDD than iRBD and controls, and correlated with UPDRS-III, MMSE, semantic fluency and visuo-perceptive scores across the proposed premotor-motor-dementia PD continuum (iRBD + PDND + PDD). CSF total-?-synuclein positively correlated with age, CSF A?, and, particularly, CSF ?, tending towards lower levels in PD (but not iRBD) vs. controls only when controlling for CSF ?. Low CSF total-?-synuclein was associated with dysfunction in phonetic-fluency (a frontal-lobe function) in PD and with frontal cortical thinning in iRBD and PDND independently of CSF ?. Conversely, the associations of high (instead of low) CSF total-?-synuclein with posterior-cortical neuropsychological deficits in PD and with posterior cortical thinning in PDD were driven by high CSF ?. These findings suggest that CSF oligomeric- and total-?-synuclein have different clinical, neuropsychological and MRI correlates across the proposed premotor-motor-dementia PD continuum. CSF total-?-synuclein correlations with CSF ? and A? support the hypothesis of an interaction among these proteins in PD, with CSF ? probably influencing the presence of high (instead of low) CSF total-?-synuclein and its correlates mostly in the setting of PD-related dementia.
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Five-year follow-up of substantia nigra echogenicity in idiopathic REM sleep behavior disorder.
Mov. Disord.
PUBLISHED: 06-30-2014
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Hyperechogenicity of the substantia nigra visualized by transcranial sonography occurs in most Parkinson's disease (PD) patients. Idiopathic rapid eye movement (REM) sleep behavior disorder (IRBD) subjects eventually develop PD and other synucleinopathies. This study was undertaken to evaluate whether in IRBD, transcranial sonography identifies subjects who convert to PD and other synucleinopathies, and whether substantia nigra echogenic size changes with time. It was a prospective study in which 55 IRBD patients underwent transcranial sonography at baseline and were invited to follow-up after 5 years. Patients were assessed by the same experienced sonographer who was blinded to clinical data and baseline transcranial sonography results, and used the same equipment and adjustments. Twenty-one (38.2%) subjects were diagnosed with a synucleinopathy (PD in 11, dementia with Lewy bodies in nine, and multiple system atrophy in one). Sensitivity of baseline substantia nigra hyperechogenicity for the development of a synucleinopathy was 42.1%, specificity 67.7%, positive predictive value 44.4%, negative predictive value 65.6%, and relative risk 1.29. No differences were detected between the first and second examination in mean size of the substantia nigra (0.20?±?0.09 cm(2) vs. 0.19?±?0.07 cm(2) ; P?=?0.777) and in percentage of patients with substantia nigra hyperechogenicity (33.3% vs. 42.8%, P?=?0.125). Transcranial sonography of the substantia nigra alone is not a useful tool to identify IRBD subjects at risk for the development of PD or a synucleinopathy after 5 years of follow-up. In IRBD, transcranial sonography cannot be used to monitor the degenerative process in the substantia nigra, because echogenicity size remains stable over time. © 2014 International Parkinson and Movement Disorder Society.
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Cortical thinning associated with mild cognitive impairment in Parkinson's disease.
Mov. Disord.
PUBLISHED: 03-17-2014
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The aim of this study was to investigate patterns of cortical atrophy associated with mild cognitive impairment in a large sample of nondemented Parkinson's disease (PD) patients, and its relation with specific neuropsychological deficits. Magnetic resonance imaging (MRI) and neuropsychological assessment were performed in a sample of 90 nondemented PD patients and 32 healthy controls. All underwent a neuropsychological battery including tests that assess different cognitive domains: attention and working memory, executive functions, memory, language, and visuoperceptual-visuospatial functions. Patients were classified according to their cognitive status as PD patients without mild cognitive impairment (MCI; n?=?43) and PD patients with MCI (n?=?47). Freesurfer software was used to obtain maps of cortical thickness for group comparisons and correlation with neuropsychological performance. Patients with MCI showed regional cortical thinning in parietotemporal regions, increased global atrophy (global cortical thinning, total gray matter volume reduction, and ventricular enlargement), as well as significant cognitive impairment in memory, executive, and visuospatial and visuoperceptual domains. Correlation analyses showed that all neuropsychological tests were associated with cortical thinning in parietotemporal regions and to a lesser extent in frontal regions. These results provide neuroanatomic support to the concept of MCI classified according to Movement Disorders Society criteria. The posterior pattern of atrophy in temporoparietal regions could be a structural neuroimaging marker of cognitive impairment in nondemented PD patients. All of the neuropsychological tests reflected regional brain atrophy, but no specific patterns were seen corresponding to impairment in distinct cognitive domains.
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Identification of blood serum micro-RNAs associated with idiopathic and LRRK2 Parkinson's disease.
J. Neurosci. Res.
PUBLISHED: 01-21-2014
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Blood-cell-free circulating micro-RNAs (miRNAs) have been proposed as potential accessible biomarkers for neurodegenerative diseases such as Parkinson's disease (PD). Here we analyzed the serum levels of 377 miRNAs in a discovery set of 10 idiopathic Parkinson's disease (IPD) patients, 10 PD patients carriers of the LRRK2 G2019S mutation (LRRK2 PD), and 10 controls by using real-time quantitative PCR-based TaqMan MicroRNA arrays. We detected candidate differentially expressed miRNAs, which were further tested in a first validation set consisting of 20 IPD, 20 LRRK2 PD, and 20 control samples. We found four statistically significant miRNAs that were downregulated in either LRRK2 or IPD (miR-29a, miR-29c, miR-19a, and miR-19b). Subsequently, we validated these findings in a third set of samples consisting of 65 IPD and 65 controls and confirmed the association of downregulated levels of miR-29c, miR-29a, and miR-19b in IPD. Differentially expressed miRNAs are predicted to target genes belonging to pathways related to ECM-receptor interaction, focal adhesion, MAPK, Wnt, mTOR, adipocytokine, and neuron projection. Results from our exploratory study indicate that downregulated levels of specific circulating serum miRNAs are associated with PD and suggest their potential use as noninvasive biomarkers for PD. Future studies should further confirm the association of these miRNAs with PD.
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Functional brain networks and cognitive deficits in Parkinson's disease.
Hum Brain Mapp
PUBLISHED: 01-10-2014
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Graph-theoretical analyses of functional networks obtained with resting-state functional magnetic resonance imaging (fMRI) have recently proven to be a useful approach for the study of the substrates underlying cognitive deficits in different diseases. We used this technique to investigate whether cognitive deficits in Parkinson's disease (PD) are associated with changes in global and local network measures. Thirty-six healthy controls (HC) and 66 PD patients matched for age, sex, and education were classified as having mild cognitive impairment (MCI) or not based on performance in the three mainly affected cognitive domains in PD: attention/executive, visuospatial/visuoperceptual (VS/VP), and declarative memory. Resting-state fMRI and graph theory analyses were used to evaluate network measures. We have found that patients with MCI had connectivity reductions predominantly affecting long-range connections as well as increased local interconnectedness manifested as higher measures of clustering, small-worldness, and modularity. The latter measures also tended to correlate negatively with cognitive performance in VS/VP and memory functions. Hub structure was also reorganized: normal hubs displayed reduced centrality and degree in MCI PD patients. Our study indicates that the topological properties of brain networks are changed in PD patients with cognitive deficits. Our findings provide novel data regarding the functional substrate of cognitive impairment in PD, which may prove to have value as a prognostic marker.
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Multiple organ involvement by alpha-synuclein pathology in Lewy body disorders.
Mov. Disord.
PUBLISHED: 01-02-2014
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Lewy body (LB) diseases are characterized by alpha-synuclein (AS) aggregates in the central nervous system (CNS). Involvement of the peripheral autonomic nervous system (pANS) is increasingly recognized, although less studied. The aim of this study was to systematically analyze the distribution and severity of AS pathology in the CNS and pANS. Detailed postmortem histopathological study of brain and peripheral tissues from 28 brain bank donors (10 with Parkinson's disease [PD], 5 with dementia with LB [DLB], and 13 with non-LB diseases including atypical parkinsonism and non-LB dementia). AS aggregates were found in the pANS of all 15 LB disease cases (PD, DLB) in stellate and sympathetic ganglia (100%), vagus nerve (86.7%), gastrointestinal tract (86.7%), adrenal gland and/or surrounding fat (53.3%), heart (100%), and genitourinary tract (13.3%), as well as in 1 case of incidental Lewy body disease (iLBD). A craniocaudal gradient of AS burden in sympathetic chain and gastrointestinal tract was observed. DLB cases showed higher amounts of CNS AS aggregates than PD cases, but this was not the case in the pANS. No pANS AS aggregates were detected in Alzheimer's disease (AD) cases with or without CNS AS aggregates. All pathologically confirmed LB disease cases including 1 case of iLBD had AS aggregates in the pANS with a craniocaudal gradient of pathology burden in sympathetic chain and gastrointestinal tract. AS was not detected in the pANS of any AD case. These findings may help in the search of peripheral AS aggregates in vivo for the early diagnosis of PD.
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Nonmotor Symptoms in LRRK2 G2019S Associated Parkinson's Disease.
PLoS ONE
PUBLISHED: 01-01-2014
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Idiopathic Parkinson's disease (IPD) and LRRK2-associated PD (LRRK2-PD) might be expected to differ clinically since the neuropathological substrate of LRRK2-PD is heterogeneous. The range and severity of extra-nigral nonmotor features associated with LRRK2 mutations is also not well-defined.
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Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients.
PLoS ONE
PUBLISHED: 01-01-2014
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To estimate the risk for developing a defined neurodegenerative syndrome in a large cohort of idiopathic REM sleep behavior disorder (IRBD) patients with long follow-up.
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The cost-effectiveness of deep brain stimulation in combination with best medical therapy, versus best medical therapy alone, in advanced Parkinsons disease.
J. Neurol.
PUBLISHED: 07-12-2013
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Parkinsons disease (PD) is a complex progressive movement disorder leading to motor and non-motor symptoms that become increasingly debilitating as the disease advances, considerably reducing quality of life. Advanced treatment options include deep brain stimulation (DBS). While clinical effectiveness of DBS has been demonstrated in a number of randomised controlled trials (RCT), evidence on cost-effectiveness is limited. The cost-effectiveness of DBS combined with BMT, versus BMT alone, was evaluated from a UK payer perspective. Individual patient-level data on the effect of DBS on PD symptom progression from a large 6-month RCT were used to develop a Markov model representing clinical progression and capture treatment effect and costs. A 5-year time horizon was used, and an incremental cost-effectiveness ratio (ICER) was calculated in terms of cost per quality-adjusted life-years (QALY) and uncertainty assessed in deterministic sensitivity analyses. Total discounted costs in the DBS and BMT groups over 5 years were £68,970 and £48,243, respectively, with QALYs of 2.21 and 1.21, giving an incremental cost-effectiveness ratio of £20,678 per QALY gained. Utility weights in each health state and costs of on-going medication appear to be the key drivers of uncertainty in the model. The results suggest that DBS is a cost-effective intervention in patients with advanced PD who are eligible for surgery, providing good value for money to health care payers.
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Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study.
Lancet Neurol
PUBLISHED: 04-03-2013
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We postulated that idiopathic rapid-eye-movement (REM) sleep behaviour disorder (IRBD) represents the prodromal phase of a Lewy body disorder and that, with sufficient follow-up, most cases would eventually be diagnosed with a clinical defined Lewy body disorder, such as Parkinsons disease (PD) or dementia with Lewy bodies (DLB).
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Peripheral neuropathy in Parkinsons disease: levodopa exposure and implications for duodenal delivery.
Parkinsonism Relat. Disord.
PUBLISHED: 02-12-2013
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In advanced Parkinsons disease (PD) patients, continuous intra-duodenal infusion of levodopa/carbidopa intestinal gel (LCIG) is an established approach in the management of motor complications that cannot be further improved by conventional oral therapy. In general, tolerability of LCIG has resembled that of oral dopaminergic therapy; however, cases of symptomatic peripheral neuropathy (PN), sometimes severe, have been reported in patients receiving LCIG. Cases are generally a sensorimotor polyneuropathy with both subacute and chronic onsets, often associated with vitamin B12 and/or B6 deficiency. Rare cases clinically resemble Guillain-Barré syndrome. In the absence of prospectively collected data on possible associations between LCIG and PN, it is prudent to explore potential mechanisms that may explain a possible relationship. The PN may be linked to use of high-dose levodopa, promoting high levels of homocysteine and methylmalonic acid or reduced absorption of vitamins essential for homocysteine metabolism. Cases of LCIG-associated PN often have responded to vitamin supplementation without need for LCIG cessation, although LCIG cessation is sometimes necessary. It may be advisable to monitor vitamin B12/B6 status before and after patients start LCIG and be vigilant for signs of PN. Prospective, large-scale, long-term studies are needed to clarify whether vitamin supplementation and routine use of a catechol-O-methyltransferase inhibitor may help prevent PN in LCIG recipients and whether these measures should be routine practice in patients with PD on high-dose oral levodopa.
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Longitudinal assessment of olfactory function in idiopathic REM sleep behavior disorder.
Parkinsonism Relat. Disord.
PUBLISHED: 02-07-2013
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Idiopathic REM sleep behavior disorder (IRBD) is an early marker of Lewy body disorders and is linked to olfactory loss. We evaluated whether olfactory function deteriorates with time in IRBD. Progressive smell loss could be a useful way in which to monitor the effect of disease-modifying interventions in subjects with IRBD.
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Selecting deep brain stimulation or infusion therapies in advanced Parkinsons disease: an evidence-based review.
J. Neurol.
PUBLISHED: 01-05-2013
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Motor complications in Parkinsons disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine.
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LRRK2 haplotype-sharing analysis in Parkinsons disease reveals a novel p.S1761R mutation.
Mov. Disord.
PUBLISHED: 10-28-2011
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Mutations in the Leucine-Rich Repeat Kinase 2 (LRRK2) gene at chromosome 12q12 are the most common genetic cause of sporadic and familial late-onset Parkinsons disease. Our aim was to identify novel LRRK2 mutations in late-onset Parkinsons disease families.
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Serial dopamine transporter imaging of nigrostriatal function in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study.
Lancet Neurol
PUBLISHED: 07-28-2011
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Serial dopamine transporter (DAT) imaging in patients with Parkinsons disease (PD) and other synucleinopathies shows progressive nigrostriatal dopaminergic dysfunction. Because idiopathic rapid-eye-movement (REM) sleep behaviour disorder (IRBD) can precede the classic symptoms of PD and other synucleinopathies, we postulated that serial DAT imaging in patients with IRBD could be used to detect decline in striatal tracer uptake, indicating progressive nigrostriatal cell degeneration.
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Inclusion and exclusion criteria for DBS in dystonia.
Mov. Disord.
PUBLISHED: 06-22-2011
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When considering a patient with dystonia for deep brain stimulation (DBS) surgery several factors need to be considered. Level B evidence has shown that all motor features and associated pain in primary generalized and segmental dystonia are potentially responsive to globus pallidus internus (GPi) DBS. However, improvements in clinical series of ? 90% may reflect methods that need improvement, and larger prospective studies are needed to address these factors. Nevertheless, to date the selection criteria for DBS-specifically in terms of patient features (severity and nature of symptoms, age, time of evolution, or any other demographic or disease aspects)--have not been assessed in a systematic fashion. In general, dystonia patients are not considered for DBS unless medical therapies have been previously and extensively tested. The vast majority of reported patients have had DBS surgery when the disease was provoking important disability, with loss of independence and impaired quality of life. There does not appear to be an upper age limit or a minimum age limit, although there are no published data regarding the outcome of GPi DBS for dystonia in children younger than 7 years of age. There is currently no enough evidence to prove that subjects with primary--generalized dystonia who undergo DBS at an early age and sooner rather than later after disease onset may gain more benefit from DBS than those undergoing DBS after the development of fixed skeletal deformities. There is no enough evidence to refuse or support consideration of DBS in patients with previous ablative procedures.
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Microarray expression analysis in idiopathic and LRRK2-associated Parkinsons disease.
Neurobiol. Dis.
PUBLISHED: 04-14-2011
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LRRK2 mutations are the most common genetic cause of Parkinsons disease (PD). We performed a whole-genome RNA profiling of putamen tissue from idiopathic PD (IPD), LRRK2-associated PD (G2019S mutation), neurologically healthy controls and one asymptomatic LRRK2 mutation carrier, by using the Genechip Human Exon 1.0-ST Array. The differentially expressed genes found in IPD revealed an alteration of biological pathways related to long-term potentiation (LTP), GABA receptor signalling, and calcium signalling pathways, among others. These pathways are mainly related with cell signalling cascades and synaptic plasticity processes. They were also altered in the asymptomatic LRRK2 mutation carrier but not in the LRRK2-associated PD group. The expression changes seen in IPD might be attributed to an adaptive consequence of a dysfunction in the dopamine transmission. The lack of these altered molecular pathways in LRRK2-associated PD patients suggests that these cases could show a different molecular response to dopamine transmission impairment.
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Rapidly progressive diffuse Lewy body disease.
Mov. Disord.
PUBLISHED: 04-11-2011
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Lewy body syndromes (mainly Parkinsons disease and dementia with Lewy bodies) share many clinical features and usually have a slowly progressive course. Some patients may show rapid symptoms progression.
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Modulation of the soleus H reflex by electrical subcortical stimuli in humans.
Exp Brain Res
PUBLISHED: 03-09-2011
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Over the past two decades, the H reflex has been used as a neural tool to assess the effect on the motoneuronal pool of conditioning volleys in supraspinal descending tracts elicited by transcranial magnetic stimulation (TMS) or auditory stimuli. However, mechanisms mediating such modulation are unclear. These hypothesized neural pathways are likely to be affected by single electrical stimulus applied through the electrodes implanted in the subthalamic nucleus for deep brain stimulation (sSTNDBS). To improve our knowledge on such mechanisms, we examined in 11 Parkinsons disease patients the effects of conditioning sSTNDBS applied contralateral and ipsilateral to the H reflex recording on the amplitude of the soleus H reflex, at interstimulus intervals (ISIs) between 0 and 110 ms. There was a significant main effect of the ISI (P<0.001) and of the sSTNDBS stimulation side (P=0.019) on the percentage change in the soleus H-reflex amplitude. Contralateral sSTNDBS modulation of the soleus H reflex resembles that of TMS in healthy subjects with two facilitation phases (at 5-20 ms and at 60 ms), while after ipsilateral sSTNDBS, there is only a single facilitation phase peaking up at 5 ms later than the first facilitation period observed with contralateral stimulation. These findings contribute to the discussion of the mechanisms underlying the excitability of the spinal alpha motoneuron pool and the modulation of the H reflex by supraspinal stimuli.
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Dysfunctions of cerebral networks precede recognition memory deficits in early Parkinsons disease.
Neuroimage
PUBLISHED: 03-09-2011
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We aimed to investigate changes in the verbal recognition memory network in patients with early Parkinsons disease (PD) without overt recognition memory alteration. Verbal recognition memory was assessed in 24 PD patients in early stages of the disease and a control group of 24 healthy subjects during fMRI data acquisition. Participants were presented with a list of 35 words before imaging, and later during fMRI scanning they were required to recognize these previously presented words. Both model-based (FEAT) and model-free (MELODIC) analyses of the fMRI data were carried out with FSL software. Memory was also assessed by means of Reys Auditory Verbal Learning Test (RAVLT). PD patients showed no difference in the fMRI recognition memory task and recognition memory assessed by the RAVLT compared to healthy controls. Model-based analysis did not show significant differences between groups. On the other hand, model-free analysis identified components that fitted the task-model and were common to all the participants, as well as components that differed between PD and healthy controls. PD patients showed decreased task-related activations in areas involved in the recognition memory network and decreased task-related deactivations in the default mode network in comparison with controls. In conclusion, model-free fMRI analysis detected alterations in functional cerebral networks involved in a verbal memory task in PD patients without evident recognition memory deficit.
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Diagnostic cutoff points for ¹²³I-MIBG myocardial scintigraphy in a Caucasian population with Parkinsons disease.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 02-01-2011
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Molecular imaging with (123)I-metaiodobenzylguanidine (MIBG) has been used in Parkinsons disease (PD), but there is no consensual index to discriminate between normal and PD patients in the Caucasian population. The purpose of this study was to determine diagnostic cutoff points in the quantification of MIBG cardiac uptake in our population of PD patients. We have also calculated the reproducibility over a range of interpretation expertise.
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123I-MIBG cardiac uptake and smell identification in parkinsonian patients with LRRK2 mutations.
J. Neurol.
PUBLISHED: 01-08-2011
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Reduced uptake of (123)I- metaiodobenzylguanidine (MIBG) on cardiac gammagraphy and impaired odor identification are markers of neurodegenerative diseases with Lewy bodies (LB) as a pathological hallmark, such as idiopathic Parkinsons disease (IPD). LRRK2 patients present with a clinical syndrome indistinguishable from IPD, but LB have not been found in some cases. Patients with such mutations could behave differently than patients with IPD with respect to MIBG cardiac uptake and olfaction. We studied 14 LRRK2 patients, 14 IPD patients matched by age, gender, disease duration and severity, and 13 age and gender matched control subjects. Olfaction was analyzed through the University of Pennsylvania Smell Identification Test (UPSIT). MIBG cardiac uptake was evaluated through the H/M ratio. The late H/M was 1.44 ± 0.31 for LRRK2 patients, 1.19 ± 0.15 for PD patients, and 1.67 ± 0.16 for control subjects. LRRK2 patients presented lower but not statistically significant MIBG cardiac uptake than controls (p = 0.08) and significant higher uptake than PD patients (p = 0.04). UPSIT mean scores were 21.5 ± 7.3 for LRRK2 patients, 18.7 ± 6.2 for IPD patients and 29.7 ± 5.7 for control subjects. UPSIT score was lower in both LRRK2 and PD than in controls. In LRRK2 patients a positive correlation was found between myocardial MIBG uptake and UPSIT scores, (R = 0.801, p < 0.001). In LRRK2 patients, MIBG cardiac uptake was less impaired than in PD; a positive correlation between MIBG cardiac uptake and UPSIT scores was observed. As MIBG cardiac reduced uptake and impaired odor identification are markers of LB pathology, this findings may represent neuropathological heterogeneity among LRRK2 patients.
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Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study [corrected].
Lancet Neurol
PUBLISHED: 09-16-2010
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Patients with idiopathic rapid-eye-movement sleep behaviour disorder (IRBD) may develop neurodegenerative conditions associated with substantia nigra dysfunction such as Parkinsons disease. In patients with Parkinsons disease, ¹²³I-2?-carbomethoxy-3?-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (¹²³I-FP-CIT) SPECT detects striatal dopamine dysfunction resulting from nigral pathology whereas transcranial sonography (TCS) shows increased substantia nigra echogenic size, even before parkinsonism is clinically evident. We postulated that these neuroimaging changes could occur in a proportion of IRBD individuals who might then be at increased risk for development of a neurodegenerative disorder associated with substantia nigra dysfunction.
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Nonlinear dynamic analysis of oscillatory repetitive movements in Parkinsons disease and essential tremor.
Mov. Disord.
PUBLISHED: 09-07-2010
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Uncertainty exists on whether Parkinsons disease (PD) and essential tremor (ET) patients have similar degree of impairment during motor tasks. We investigated this problem by analyzing nonlinear dynamics of repetitive movements in 21 control subjects, 33 mild-moderate PD patients, and 18 ET patients. Accelerometer signals were recorded during finger tapping and unbounded forearm movements between two points, and processed with moving average filtering to generate a new signal consisting of the temporal distance between consecutive cycles. We calculated: mean interpeak interval (slowness), interpeak interval variability (irregularity), and beat decay (BD) of the auto mutual information (AMI) value, which estimates signal predictability by measuring the loss of signal information over a timescale. Both PD and ET had longer interpeak interval (except for finger tapping), higher interpeak interval variability, and higher BD-AMI values than controls (P ? 0.007, all comparisons). ET patients had higher BD-AMI values than PD (P = 0.003). BD-AMI was the parameter that discriminated better between subjects (diagnosis accuracies about 80%). No differences existed between PD patients with and without tremor or between PD or ET patients with different disease stages, for any parameter. Evaluation of nonlinear dynamics of oscillatory repetitive movements is a feasible and promising tool for studying movement physiology. Movement performance is more predictable in PD and ET than in controls, even in early disease stages. Slowness and irregularity of movement in PD and ET cannot be fully explained by tremor. Some common pathogenic mechanisms leading to bradykinesia may contribute to this impairment.
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A tool to improve pre-selection for deep brain stimulation in patients with Parkinsons disease.
J. Neurol.
PUBLISHED: 09-02-2010
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Determining the eligibility of patients with Parkinsons disease (PD) for deep brain stimulation (DBS) can be challenging for general (non-specialised) neurologists. We evaluated the use of an online screening tool (Stimulus) that aims to support appropriate referral to a specialised centre for the further evaluation of DBS. Implementation of the tool took place via an ongoing European multicentre educational programme, currently completed in 15 DBS centres with 208 referring neurologists. Use of the tool in daily practice was monitored via an online data capture programme. Selection decisions of patients referred with the assistance of the Stimulus tool were compared to those of patients outside the screening programme. Three years after the start of the programme, 3,128 patient profiles had been entered. The intention for referral was made for 802 patients and referral intentions were largely in accordance with the tool recommendations. Follow-up at 6 months showed that actual referral took place in only 28%, predominantly due to patients reluctance to undergo brain surgery. In patients screened with the tool and referred to a DBS centre, the acceptance rate was 77%, significantly higher than that of the unscreened population (48%). The tool showed a sensitivity of 99% and a specificity of 12% with a positive and negative predictive value of 79 and 75%, respectively. The Stimulus tool is useful in assisting general neurologists to identify appropriate candidates for DBS consideration. The principal reason for not referring potentially eligible patients is their reluctance to undergo brain surgery.
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Olfactory impairment in Parkinsons disease and white matter abnormalities in central olfactory areas: A voxel-based diffusion tensor imaging study.
Mov. Disord.
PUBLISHED: 07-30-2010
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Olfactory dysfunction is known to occur before the appearance of the classical motor signs in Parkinsons disease (PD) and diffusion tensor imaging (DTI) studies in PD have reported fractional anisotropy (FA) reductions in the early disease stages. We aimed to investigate the relationship between olfactory dysfunction and white matter (WM) FA of central olfactory areas in early PD. Twenty-four patients at Hoehn and Yahr stages I and II and 24 healthy controls matched by age, gender and years of education participated in this study. DTI was acquired at a 3 Tesla scanner and odor identification was assessed using the University of Pennsylvania Smell Identification Test (UPSIT). We performed FA voxelwise group comparisons in the central olfactory structures using tract-based spatial statistics (TBSS) and correlation analyses between FA values in these central olfactory areas and UPSIT scores. Patients with severe microsmia (UPSIT between 19 and 25) and anosmia (UPSIT lower or equal to 18) had lower FA values than PD patients with mild/moderate or no olfactory dysfunction (UPSIT between 26 and 40) and healthy controls in the WM adjacent to gyrus rectus. In addition, patients with anosmia had reduced FA in the WM surrounding primary olfactory areas in comparison with healthy controls. FA values in the WM adjacent to primary olfactory cortex and right gyrus rectus correlated with UPSIT scores in the PD group. This study demonstrates, for the first time, that microstructural WM reductions are present in the central olfactory system of early stage PD patients and that these reductions are associated with reduced ability to smell.
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High cerebrospinal tau levels are associated with the rs242557 tau gene variant and low cerebrospinal ?-amyloid in Parkinson disease.
Neurosci. Lett.
PUBLISHED: 07-21-2010
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Cerebrospinal fluid (CSF) tau and phospho-tau levels have been associated with certain tau gene variants and low CSF amyloid-? (A?) levels in Alzheimer disease (AD), constituting potential biomarkers of molecular mechanisms underlying neurodegeneration. We aimed to assess whether such CSF-genetic endophenotypes are also present in Parkinson disease (PD). CSF tau, phospho-tau and A? levels were obtained from 38 PD patients (19 with dementia) using specific ELISA techniques. All cases were genotyped for a series of tau gene polymorphisms (rs1880753, rs1880756, rs1800547, rs1467967, rs242557, rs2471738 and rs7521). The A-allele rs242557 polymorphism was the only tau gene variant significantly associated with higher CSF tau and phospho-tau levels, under both dominant and dose-response model. This association depended on the presence of dementia, and was only observed in individuals with low (<500pg/mL) CSF A? levels. Such genetic-CSF endophenotypes are probably a reflection of the presence of AD-like molecular changes in part of PD patients in the setting of dementia.
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[Intraduodenal infusion of levodopa].
Rev Neurol
PUBLISHED: 06-23-2010
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In the advanced stages of Parkinsons disease (PD), the conventional orally-administered pharmacological treatment can prove to be insufficient to control the motor complications associated with the disease. One of the causes involved in the genesis of the motor fluctuations that are observed in PD is the variable absorption of the medication due to an irregular or erratic emptying of the gastric content. Today, a method of therapy is now available that allows levodopa to be administered directly into the duodenum at a continuous rate by a perfusor. The medication is applied through a duodenal catheter implanted by means of a percutaneous endoscopic gastrostomy. This new form of administration has been marketed under the name of Duodopa, which is a pharmaceutical form of levodopa in a micronised suspension in a thickening gel consisting of sodium carmelose. It is presented in combination with levodopa (20 mg/mL) and a dopa decarboxylase inhibitor, carbidopa (5 mg/mL). Duodopa has proved to be effective in reducing the percentage of off time and in diminishing the periods with disabling dyskinesias. This therapy has also proved to be useful for relieving certain non-motor aspects associated with PD and presents fewer limitations regarding indication for advanced PD patients than those that usually exist for the case of deep brain stimulation. Although the therapy has proved to be effective, it is not free of complications arising from malfunctioning of the infusion system or in relation to the percutaneous endoscopic gastrostomy.
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Late-stage Parkinsons disease: the Barcelona and Lisbon cohort.
J. Neurol.
PUBLISHED: 02-09-2010
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Studies of late stages of Parkinsons disease (LS-PD) are limited. To provide an adequate health plan for patients in these most advanced stages, accurate information on their clinical condition is necessary. We characterize clinical features and medication use of LS-PD. A cross-sectional study of LS-PD stage 4 or 5 of Hoehn and Yahr during on states is presented in this paper. Demographics, clinical features and medication data were obtained using a structured questionnaire and physical examination. Patients were asked to grade the perceived impact of symptoms on their health status. Fifty patients (mean age 74.1 years and mean disease duration 17.9 years) were studied. Severe akinetic symmetric parkinsonism was present in most, with negligible rigidity and tremor, and most patients were wheelchair-bound. Severe postural instability and freezing of gait, causing frequent falls and fractures, and prominent dysarthria and dysphagia dominated the motor syndrome. Levodopa remained effective in most patients in relieving motor symptoms including tremor. Motor fluctuations and dyskinesias were present in 78 and 62% of patients, respectively, but were not perceived as disabling. All had neuropsychiatric and dysautonomic symptoms. Visual hallucinations were present in 44%, depression in 62% and dementia in 50%. Lack of tremor (p < 0.01) and absence of depression (p < 0.01) were independently associated with dementia (R(2) = 45%). Symptoms causing greatest impact on perceived health status were falls, gait unsteadiness, urinary dysfunction and sweats. Motor and non-motor non-levodopa responsive problems were frequent and the main cause of disability. Fluctuations and dyskinesias were frequent though not disabling. Dementia is not unavoidable in these very late stages.
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Differential progression of brain atrophy in Parkinsons disease with and without visual hallucinations.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 12-03-2009
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To determine the course of cognitive deficits and the regional progression of brain atrophy in patients with Parkinsons disease (PD) with and without visual hallucinations (VH).
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Cerebrospinal hypocretin, daytime sleepiness and sleep architecture in Parkinsons disease dementia.
Brain
PUBLISHED: 10-25-2009
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Excessive daytime sleepiness is common in Parkinsons disease and has been associated with Parkinsons disease-related dementia. Narcoleptic features have been observed in Parkinsons disease patients with excessive daytime sleepiness and hypocretin cell loss has been found in the hypothalamus of Parkinsons disease patients, in association with advanced disease. However, studies on cerebrospinal fluid levels of hypocretin-1 (orexin A) in Parkinsons disease have been inconclusive. Reports of sleep studies in Parkinsons disease patients with and without excessive daytime sleepiness have also been disparate, pointing towards a variety of causes underlying excessive daytime sleepiness. In this study, we aimed to measure cerebrospinal fluid hypocretin-1 levels in Parkinsons disease patients with and without dementia and to study their relationship to dementia and clinical excessive daytime sleepiness, as well as to describe potentially related sleep architecture changes. Twenty-one Parkinsons disease patients without dementia and 20 Parkinsons disease patients with dementia, along with 22 control subjects without sleep complaints, were included. Both Epworth sleepiness scale, obtained with the help of the caregivers, and mini-mental state examination were recorded. Lumbar cerebrospinal fluid hypocretin-1 levels were measured in all individuals using a radio-immunoassay technique. Additionally, eight Parkinsons disease patients without dementia and seven Parkinsons disease patients with dementia underwent video-polysomnogram and multiple sleep latencies test. Epworth sleepiness scale scores were higher in Parkinsons disease patients without dementia and Parkinsons disease patients with dementia than controls (P < 0.01) and scores >10 were more frequent in Parkinsons disease patients with dementia than in Parkinsons disease patients without dementia (P = 0.04). Cerebrospinal fluid hypocretin-1 levels were similar among groups (controls = 321.15 +/- 47.15 pg/ml; without dementia = 300.99 +/- 58.68 pg/ml; with dementia = 309.94 +/- 65.95 pg/ml; P = 0.67), and unrelated to either epworth sleepiness scale or mini-mental state examination. Dominant occipital frequency awake was slower in Parkinsons disease patients with dementia than Parkinsons disease patients without dementia (P = 0.05). Presence of slow dominant occipital frequency and/or loss of normal non-rapid eye movement sleep architecture was more frequent among Parkinsons disease patients with dementia (P = 0.029). Thus, excessive daytime sleepiness is more frequent in Parkinsons disease patients with dementia than Parkinsons disease patients without dementia, but lumbar cerebrospinal fluid hypocretin-1 levels are normal and unrelated to severity of sleepiness or the cognitive status. Lumbar cerebrospinal fluid does not accurately reflect the hypocretin cell loss known to occur in the hypothalamus of advanced Parkinsons disease. Alternatively, mechanisms other than hypocretin cells dysfunction may be responsible for excessive daytime sleepiness and the sleep architecture alterations seen in these patients.
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Cerebrospinal tau, phospho-tau, and beta-amyloid and neuropsychological functions in Parkinsons disease.
Mov. Disord.
PUBLISHED: 10-02-2009
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Alzheimers disease (AD)-pathology may play a role in Parkinsons disease (PD)-related dementia (PDD). The aim of this study was to assess cerebrospinal fluid (CSF) levels of tau, phospho-tau, and beta-amyloid, proposed AD biomarkers, and their relationship with cognitive function in PD. Forty PD patients [20 nondemented (PDND); 20 PDD] and 30 controls underwent CSF tau, phospho-tau, and beta-amyloid analysis using specific ELISA techniques. All PD patients and 15 controls underwent neuropsychological testing of fronto-subcortical (attention, fluency) and neocortical (memory, naming, visuoperceptive) functions. CSF markers levels were compared between groups, and compared and correlated with neuropsychological measures in PDND and PDD separately and as a continuum (PD). CSF tau and phospho-tau were higher in PDD than in PDND and controls (P < 0.05). CSF beta-amyloid ranged from high (controls) to intermediate (PDND) and low (PDD) levels (P < 0.001). In all PD and PDD patients, high CSF tau and phospho-tau were associated with impaired memory and naming. In PDND, CSF beta-amyloid was related with phonetic fluency. These findings suggest underlying AD-pathology in PDD in association with cortical cognitive dysfunction, and that low CSF beta-amyloid in PDND patients with impaired phonetic fluency can constitute an early marker of cognitive dysfunction.
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Neuroanatomical correlates of impaired decision-making and facial emotion recognition in early Parkinsons disease.
Eur. J. Neurosci.
PUBLISHED: 09-04-2009
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Decision-making and recognition of emotions are often impaired in patients with Parkinsons disease (PD). The orbitofrontal cortex (OFC) and the amygdala are critical structures subserving these functions. This study was designed to test whether there are any structural changes in these areas that might explain the impairment of decision-making and recognition of facial emotions in early PD. We used the Iowa Gambling Task (IGT) and the Ekman 60 faces test which are sensitive to the integrity of OFC and amygdala dysfunctions in 24 early PD patients and 24 controls. High-resolution structural magnetic resonance images (MRI) were also obtained. Group analysis using voxel-based morphometry (VBM) showed significant and corrected (P < 0.05 FEW-small volume correction) gray matter (GM) loss in the right amygdala and bilaterally in the OFC in PD patients. Volumetric analyses were also performed but did not yield significant differences between groups. Left lateral GM volume in OFC showed a slight correlation with the IGT, and bilateral OFC GM was strongly correlated with Ekman test performance in PD patients. We conclude that: (i) impairment in decision-making and recognition of facial emotions occurs at the early stages of PD, (ii) these neuropsychological deficits are accompanied by degeneration of OFC and amygdala, and (iii) bilateral OFC reductions are associated with impaired recognition of emotions, and GM volume loss in left lateral OFC is related to decision-making impairment in PD.
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Midbrain hyperechogenicity in idiopathic REM sleep behavior disorder.
Mov. Disord.
PUBLISHED: 08-01-2009
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Recent studies have reported an increased risk to develop Parkinsons disease (PD) in patients with idiopathic RBD (iRBD). Midbrain hyperechogenicity is a common transcranial sonography (TCS) finding in PD and has been suggested as a PD risk-marker in nonparkinsonian subjects. The objective of this study is to assess midbrain echogenicity by TCS in patients with iRBD and compare the findings with the healthy controls. TCS was performed in 55 iRBD patients and in 165 age and sex-matched controls. The area of echogenicity in the SN region in the iRBD group was significantly increased compared with the control group (P < 0.001). About 19 (37.3%) of patients with iRBD were found to have SN hyperechogenicity when compared with 16 (10.7%) of the controls (P < 0.001). This is the first case-control study assessing midbrain echogenicity in a large iRBD cohort compared to age- and sex-matched healthy individuals. The finding of an increased prevalence of hyperechogenicity in a subgroup of individuals with a priori increased risk for PD supports the potential role of hyperechogenicity as a risk marker for PD. The prospective follow-up of this iRBD cohort is needed to establish if those with midbrain hyperechogenicity will go on to develop clinically defined PD or not.
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Different MAPT haplotypes are associated with Parkinsons disease and progressive supranuclear palsy.
Neurobiol. Aging
PUBLISHED: 02-23-2009
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The H1 MAPT haplotype in the 17q21 chromosomal region has been associated with several neurodegenerative diseases. Some reports have suggested that there is an association between genetic variants within the H1 haplotype with Parkinsons disease (PD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Here we report a genetic association study using seven SNPs located along the 17q21 region, in PD patients and controls. In addition, we compared these results with a dataset of previously published PSP/CBD patients from the same population. Our results show that the H1-rs242557(G) allele sub-haplotype is increased in PD (p=0.005), while the H1-rs242557(A) allele sub-haplotype is increased in PSP/CBD (p=0.0002), comparing to controls. The rs242557 polymorphism could act modulating the phenotypic expressivity of the H1 risk on these parkinsonisms. The location of this polymorphism in the 5 regulatory region of MAPT gene suggests the presence of a functional mechanism involved in the variation of MAPT expression levels.
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Progression of cortical thinning in early Parkinsons disease.
Mov. Disord.
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The aim of this study was to investigate the progression of cortical thinning and gray-matter (GM) volume loss in early Parkinsons disease (PD). MRI and neuropsychological assessment were obtained at baseline and follow-up (mean ± standard deviation = 35.50 ± 1.88 months) in a group of 16 early-PD patients (H & Y stage ?II and disease duration ?5 years) and 15 healthy controls matched for age, gender, and years of education. FreeSurfer software was used for the analysis of cortical thickness as well as for cortical and subcortical volumetric analyses. Voxel-based morphometry analysis was performed using SPM8. Compared to controls, PD patients showed greater regional cortical thinning in bilateral frontotemporal regions as well as greater over-time total GM loss and amygdalar volume reduction. PD patients and controls presented similar over-time changes in cognitive functioning. In early-PD patients, global GM loss, amygdalar atrophy, and cortical thinning in frontotemporal regions are specifically associated with the PD-degenerative process.
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Progressive changes in a recognition memory network in Parkinsons disease.
J. Neurol. Neurosurg. Psychiatr.
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In a previous functional MRI (fMRI) study, we found that patients with Parkinsons disease (PD) presented with dysfunctions in the recruitment of recognition memory networks. We aimed to investigate the changes in these networks over time.
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A loud auditory stimulus overcomes voluntary movement limitation in cervical dystonia.
PLoS ONE
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Patients with cervical dystonia (CD) present with an impaired performance of voluntary neck movements, which are usually slow and limited. We hypothesized that such abnormality could involve defective preparation for task execution. Therefore, we examined motor preparation in CD patients using the StartReact method. In this test, a startling auditory stimulus (SAS) is delivered unexpectedly at the time of the imperative signal (IS) in a reaction time task to cause a faster execution of the prepared motor programme. We expected that CD patients would show an abnormal StartReact phenomenon.
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Cost analysis of the treatments for patients with advanced Parkinsons disease: SCOPE study.
J Med Econ
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To perform a comparative long-term analysis of the associated healthcare costs for the therapeutic options in advanced Parkinsons Disease (PD): deep brain stimulation (DBS), continuous duodenal levodopa-carbidopa infusion (CDLCI), and continuous subcutaneous apomorphine infusion (CSAI).
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Phenotypic variability within the inclusion body spectrum of basophilic inclusion body disease and neuronal intermediate filament inclusion disease in frontotemporal lobar degenerations with FUS-positive inclusions.
J. Neuropathol. Exp. Neurol.
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Basophilic inclusion body disease and neuronal intermediate filament inclusion disease (NIFID) are rare diseases included among frontotemporal lobar degenerations with FUS-positive inclusions (FTLD-FUS). We report clinical and pathologic features of 2 new patients and reevaluate neuropathologic characteristics of 2 previously described cases, including an early-onset case of basophilic inclusion body disease (aged 38 years) with a 5-year disease course and abundant FUS-positive inclusion bodies and 3 NIFID cases. One NIFID case (aged 37 years) presented with early-onset psychiatric disturbances and rapidly progressive cognitive decline. Two NIFID cases had later onset (aged 64 years and 70 years) and complex neurologic deficits. Postmortem neuropathologic studies in late-onset NIFID cases disclosed ?-internexin-positive "hyaline conglomerate"-type inclusions that were positive with 1 commercial anti-FUS antibody directed to residues 200 and 250, but these were negative to amino acids 90 and 220 of human FUS. Early-onset NIFID had similar inclusions that were positive with both commercial anti-FUS antibodies. Genetic testing performed on all cases revealed no FUS gene mutations. These findings indicate that phenotypic variability in NIFID, including clinical manifestations and particular neuropathologic findings, may be related to the age at onset and individual differences in the evolution of lesions.
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Age at onset in LRRK2-associated PD is modified by SNCA variants.
J. Mol. Neurosci.
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Mutations in the leucine-rich repeat kinase 2 (LRRK2) and ?-synuclein (SNCA) genes are known genetic causes of Parkinsons disease (PD). Recently, a genetic variant in SNCA has been associated with a lower age at onset in idiopathic PD (IPD). We genotyped the SNCA polymorphism rs356219 in 84 LRRK2-associated PD patients carrying the G2019S mutation. We found that a SNCA genetic variant is associated with an earlier age at onset in LRRK2-associated PD. Our results support the notion that SNCA variants can modify the pathogenic effect of LRRK2 mutations as described previously for IPD.
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Grey matter volume correlates of cerebrospinal markers of Alzheimer-pathology in Parkinsons disease and related dementia.
Parkinsonism Relat. Disord.
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Regional brain grey matter volume (GMV) reductions and abnormal cerebrospinal fluid (CSF) levels of ? and A?, extensively studied as biomarkers of Alzheimers disease (AD), have also been reported in Parkinsons disease (PD) and related dementia (PDD). However, the relationship between these CSF and MRI biomarkers in PD and PDD remains unexplored. We studied these associations in 33 PD patients (18 with no dementia [PDND]; 15 fulfilling PDD criteria) and 12 neurologically unimpaired controls, with neuropsychological assessment, CSF ELISA studies, and voxel-based morphometry (VBM) analysis of high-field brain MRI. Neuropsychological assessment showed a gradation in cognitive performance from controls to PDND (significantly worse on visuospatial performance) and then to PDD (more impaired on memory, naming, fluency and visuospatial functions). No CSF-VBM correlations were found in controls or PDND patients. In contrast, in the analysis of both the PDD subgroup and the entire PD (PDND + PDD) sample, we found significant negative CSF-GMV correlations for ? and phospho-? and significant positive CSF-GMV correlations for A? in mostly frontal and temporal structures. The correlations in the entire PD sample fitted with a linear model and were thus unlikely to have been driven solely by the PDD subgroup. Additionally, an association between both the CSF markers and the CSF-associated GMV reductions with several neuropsychological functions was found. We interpret that CSF markers of AD pathology are associated with VBM-measures of brain atrophy in PD-related dementia and within the PD cognitive continuum, and deserve further attention as putative biomarkers of cognitive impairment and dementia in PD.
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Use of electroconvulsive therapy in Parkinson disease with residual axial symptoms partially unresponsive to L-dopa: a pilot study.
J ECT
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Mental dysfunction and especially gait disorders, such as freezing and postural instability in "on phase," are partially unresponsive to dopaminergic therapy late in the course of Parkinson disease (PD). Some of them have been related to decreased sensitivity of postsynaptic dopaminergic receptors, and it is known that electroconvulsive therapy (ECT) enhances the sensitivity of these receptors. The aim of this study was to determine the efficacy and safety of ECT in patients with advanced Parkinson disease with symptoms partially unresponsive to L-dopa.
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Ziprasidone versus clozapine in the treatment of psychotic symptoms in Parkinson disease: a randomized open clinical trial.
Clin Neuropharmacol
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To compare the efficacy and safety of ziprasidone versus clozapine in patients with psychotic symptoms in Parkinson disease.
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Polyneuropathy while on duodenal levodopa infusion in Parkinsons disease patients: we must be alert.
J. Neurol.
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Some reports have emerged describing the occurrence of Guillain-Barré syndrome and polyneuropathy related to vitamin B(12) deficiency in some patients with Parkinsons disease (PD) treated with continuous duodenal levodopa infusion. We describe five PD patients who developed axonal polyneuropathy and vitamin B(12) deficiency while on treatment with duodenal levodopa infusion, review other cases reported in the literature, discuss potential etiologic factors, and suggest a possible algorithm for the management and prevention of this complication. One case of Guillain-Barré syndrome and at least 12 cases of polyneuropathy related to vitamin B(12) deficiency have been reported in PD patients treated with duodenal levodopa infusion. Levodopa gel infusion may induce a decrease in vitamin B(12) levels, leading to peripheral neuropathy. Additional pathogenetic mechanisms include alterations related to the metabolism of L: -dopa, abnormal L: -dopa absorption, and direct neurotoxicity of L: -dopa at high doses. Vitamin B(12) supplementation may need to be considered in PD patients on duodenal levodopa infusion therapy. Vitamin B(12) deficiency in patients on duodenal levodopa infusion therapy may be more frequent than the published data suggest. We must be alert.
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